Infections, Bacterial Clinical Trial
Official title:
A Phase I; Multi-Center; Open-Label (Parts 1 and 2); Randomized, Double-Blind, Placebo-Controlled (Part 3); Single-Dose; 3-Part Study to Evaluate the Relative Bioavailability of Three Formulations in Healthy Subjects, Food Effect on Tablet Formulation in Healthy Subjects, and Pharmacokinetics of Gepotidacin (GSK2140944) in Japanese Subjects in Fasted and Fed States
| Verified date | September 2020 |
| Source | GlaxoSmithKline |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study is divided in 2 parts. Part 1a is being conducted to evaluate the safety,
tolerability, and relative bioavailability of the 2 free base tablet formulations (roller
compacted [RC] and high shear wet granulation [HSWG]) compared to the reference capsule
formulation under fasted conditions. This is a 3-period; cross-over study that will guide
which gepotidacin formulation will be used for future studies. Following review of
pharmacokinetic (PK) and safety data in Part 1a, a decision will be made whether to proceed
with Parts 1b and 2.
Part 1b is a 2-period, cross-over study and will assess the effect of food on the PK of the
selected gepotidacin tablet formulation from Part 1a. In Part 2, the PK of the selected
gepotidacin tablet formulation from Part 1a in Japanese (2a) and Chinese (2b) subjects will
be evaluated under fasted conditions.
The duration of the study (from Screening to the Follow-up visit) will be approximately 44
days (Part 1a), 41 days (Part 1b) and 38 days (Part 2a and 2b each), respectively. The
approximate number of subjects enrolled in Part 1a will be 27 (9 subjects in each of the 3
treatment sequences), 16 in Part 1b (8 subjects in each of the 2 treatment sequences) and 12
Japanese and 12 Chinese subjects in Part 2a and 2b, respectively.
| Status | Completed |
| Enrollment | 48 |
| Est. completion date | October 17, 2017 |
| Est. primary completion date | October 17, 2017 |
| Accepts healthy volunteers | Accepts Healthy Volunteers |
| Gender | All |
| Age group | 18 Years to 64 Years |
| Eligibility |
Inclusion Criteria - Male or female subjects between 18 and 64 years of age inclusive, at the time of signing the informed consent. - Healthy as determined by the investigator based on medical history, clinical laboratory results (serum chemistry, hematology, urinalysis, and serology), vital sign measurements, 12-lead ECG results, and physical examination findings. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. - Additional inclusion criteria for Japanese subjects (Part 2a only): the subject was a non-naturalized Japanese citizen and held a Japanese passport, the subject had 2 Japanese parents and 4 Japanese grandparents who were all non naturalized Japanese citizens, as confirmed by interview and the subject had been living outside of Japan for up to 10 years as confirmed by interview. - Additional inclusion criteria for Chinese subjects (Part 2b only): the subject was a non-naturalized Chinese citizen and held a Chinese passport, the subject had 2 Chinese parents and 4 Chinese grandparents who were all non naturalized Chinese citizens, as confirmed by interview, the subject had been living outside of China for up to 10 years as confirmed by interview. - Body weight for subjects in Part 1a and 1b: more than equal to (>=) 50 kilogram (kg) and body mass index (BMI) within the range 19 and 32 kilogram per meter square (kg/m^2), inclusive and for Japanese and Chinese subjects (Part 2a and 2b): >=50 kg and BMI within the range 18 and 32 kg/m^2, inclusive. - Male or female: a female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin test, not lactating, and at least one of the following conditions applies. Non-reproductive potential defined as: pre-menopausal females with one of the following: documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, documented bilateral oophorectomy and postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle-stimulating hormone and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential from 30 days prior to the first dose of study medication and until completion of the Follow-up visit. - Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Exclusion Criteria - Subject has a clinically significant abnormality in past medical history or at the Screening physical examination that in the investigator's opinion may place the subject at risk or interfere with outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastrointestinal, respiratory, hematologic, or immunologic disease. - Subject has any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study drug, or any other condition that may place the subject at risk, in the opinion of the investigator. - QTc more than (>) 450 millisecond (msec). - Use of a systemic antibiotic within 30 days of Screening. - Within 2 months before Screening, either a confirmed history of Clostridium difficile diarrhea infection or a past positive Clostridium difficile toxin test. - Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). - History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic uses heparin to maintain intravenous cannula patency). - Subjects cannot use any over-the-counter, or prescription medication (except for hormonal contraceptives and/or acetaminophen), vitamin supplement, or herbal medication within 7 days (or 5 half-lives, whichever is longer) before dosing and during the study. - History of regular alcohol consumption within 6 months of screening defined as an average weekly intake of >21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 milliliter (mL) of full strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine. - Urinary cotinine level indicative of smoking or history or regular use of tobacco- or nicotine containing products within 3 months before screening. - History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation. - Presence of hepatitis B surface antigen, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. - Female subject has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic. - ALT >1.5×upper limit of normal (ULN) - Bilirubin >1.5×ULN (isolated bilirubin >1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin less than [<] 35 percent [%]). - Urinalysis positive for blood without other cause identified. - A positive pre-study drug/alcohol screen. - A positive test for human immunodeficiency virus antibody. - Subject has clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at Screening or Day -1. - Donation of blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. - Previous exposure to gepotidacin within 12 months prior to the first dosing day. - Exclusion criteria for screening and baseline 12-lead ECG (a single repeat is allowed for eligibility determination): male subjects with heart rate <40 and >100 beats per minute (bpm), female subjects with heart rate <50 and >100 bpm, PR interval <120 and >220 msec for male and female subjects, QRS duration <70 and >120 msec in both male and female subjects and corrected QT interval using Bazett's formula (QTcB) or corrected QT interval using Fridericia's formula (QTcF) >450 msec in both male and female subjects. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block [second degree or higher], Wolf Parkinson White syndrome), sinus pauses >3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GlaxoSmithKline medical monitor, will interfere with the safety of the individual subject. - The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). - Subject is unable to comply with all study procedures, in the opinion of the investigator. - The subject should not participate in the study, in the opinion of the investigator or sponsor. |
| Country | Name | City | State |
|---|---|---|---|
| United States | GSK Investigational Site | Anaheim | California |
| United States | GSK Investigational Site | Austin | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| GlaxoSmithKline |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Area Under the Concentration-time Curve From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of Plasma Gepotidacin for Part 1a | Blood samples for pharmacokinetic (PK) analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 milliliters (mL) of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. The PK Parameter Population consisted of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. Statistics has been presented on geometric least square (LS) means. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Area Under the Concentration-time Curve (AUC) From Time 0 (Pre-dose) to Time of the Last Quantifiable Concentration (AUC [0-t]) of Plasma Gepotidacin for Part 1a | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Statistics has been presented on geometric LS means. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Relative Bioavailability of Drug (Frel) of Plasma Gepotidacin for Part 1a | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. NA indicates data was not available as this was the reference capsule the Frel of each tablet type was being compared to. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Maximum Observed Concentration (Cmax) Determined Directly From the Concentration Time Data of Plasma Gepotidacin for Part 1a | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Statistics has been presented on geometric LS means. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Time to First Occurrence of Cmax (Tmax) of Plasma Gepotidacin for Part 1a | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of Plasma Gepotidacin for Part 1a | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Terminal Phase Half-life (t1/2) of Plasma Gepotidacin for Part 1a | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Total Unchanged Drug (Total Amount of Drug Excreted in Urine [Ae Total]) for Part 1a | PK urine samples were collected at 0 (predose), 0 to 2, 2 ot 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours | |
| Primary | Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Plasma Gepotidacin for Part 1a | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours | |
| Primary | Renal Clearance of Drug in Urine (CLr) for Part 1a | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours | |
| Primary | Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Only those participants available at the specific time points were analyzed (represented by n = X in the category titles). | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours | |
| Primary | Area Under the Urine Concentration-time Curve Over Time 0 (Pre-dose) to 12 Hours (AUC [0-12]) for Part 1a | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | Area Under the Urine Concentration-time Curve Over Time 0 (Pre-dose) to 24 Hours (AUC [0-24]) After Dosing for Part 1a | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours | |
| Primary | Area Under the Urine Concentration-time Curve Over Time 0 (Pre-dose) to 48 Hours (AUC [0-48]) After Dosing for Part 1a | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Only those participants with data available at the indicated time point were analyzed. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours | |
| Primary | AUC (0-infinity) of Plasma Gepotidacin for Part 1b | Blood samples for PK analysis of gepotidacin was planned to be collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1b. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | AUC (0-t) of Plasma Gepotidacin for Part 1b | Blood samples for PK analysis of gepotidacin was planned to be collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1b. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Cmax of Plasma Gepotidacin for Part 1b | Blood samples for PK analysis of gepotidacin was planned to be collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1b. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Tmax of Plasma Gepotidacin for Part 1b | Blood samples for PK analysis of gepotidacin was planned to be collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1b. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Tlag of Plasma Gepotidacin for Part 1b | Blood samples for PK analysis of gepotidacin was planned to be collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1b. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | t1/2 of Plasma Gepotidacin for Part 1b | Blood samples for PK analysis of gepotidacin was planned to be collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1b. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | AUC (0-infinity) of Plasma Gepotidacin for Part 2 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 2. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | AUC (0-t) of Plasma Gepotidacin for Part 2 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 2. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Cmax of Plasma Gepotidacin for Part 2 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 2. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Tlag of Plasma Gepotidacin for Part 2 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 2. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Tmax of Plasma Gepotidacin for Part 2 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 2. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | t1/2 of Plasma Gepotidacin for Part 2 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 2. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Total Unchanged Drug (Ae Total) for Part 2 | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | Ae (t1-t2) for Part 2 | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | AUC (0-12) for Part 2 | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | AUC (0-24) for Part 2 | PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | AUC (0-48) for Part 2 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | fe% for Part 2 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | CLr for Part 2 | PK urine samples were collected at pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | AUC (0-infinity) of Plasma Gepotidacin for Part 3 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 3. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | AUC (0-t) of Plasma Gepotidacin for Part 3 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 3. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Cmax of Plasma Gepotidacin for Part 3 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 3. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Tmax of Plasma Gepotidacin for Part 3 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 3. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Tlag of Plasma Gepotidacin for Part 3 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 3. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | t1/2 of Plasma Gepotidacin for Part 3 | Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 3. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period | |
| Primary | Total Unchanged Drug (Ae Total) for Part 3 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours | |
| Primary | Urine Ae (t1-t2) for Part 3 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Only those participants available at the specific time points were analyzed (represented by n = X in the category titles). | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | Urine AUC (0-12) for Part 3 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | Urine AUC (0-24) for Part 3 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | Urine AUC (0-48) for Part 3 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | fe% for Part 3 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Primary | CLr for Part 3 | PK urine samples were collected at pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher | Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours. | |
| Secondary | Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) for Part 1a | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Participants with non-serious AEs and SAEs has been reported. Safety Population comprised of all participants who received at least 1 dose of study medication and had at least 1 post dose safety assessment. | Up to 14 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Glucose, Serum Calcium, Serum Carbon Dioxide, Serum Chloride, Serum Potassium, Serum Sodium and Serum Urea Nitrogen for Part 1a | Blood samples were collected for the assessment of chemistry parameters namely serum glucose, serum calcium, serum carbon dioxide, serum chloride, serum potassium, serum sodium and serum urea nitrogen for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Alanine Aminotransferase (ALT), Serum Alkaline Phosphatase (AP), Serum Aspartate Aminotransferase (AST) and Serum Creatinine Kinase (CK) for Part 1a | Blood samples were collected for the assessment of chemistry parameters namely serum ALT, serum AP, serum AST and serum CK for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Albumin and Serum Protein for Part 1a | Blood samples were collected for the assessment of chemistry parameters namely serum albumin and serum protein for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Bilirubin, Serum Creatinine and Serum Direct Bilirubin for Part 1a | Blood samples were collected for the assessment of chemistry parameters namely serum bilirubin, serum creatinine and serum direct bilirubin Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameters Blood Basophils, Blood Eosinophils, Blood Leukocytes, Blood Lymphocytes, Blood Monocytes, Blood Neutrophils and Blood Platelets for Part 1a | Blood samples were collected for the assessment of hematology parameters namely blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils and blood platelets for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameters Blood Erythrocyte (Ery.) Mean Corpuscular Hemoglobin Concentration (MCHC) and Blood Hemoglobin for Part 1a | Blood samples were collected for the assessment of hematology parameters namely blood Ery. MCHC and blood hemoglobin for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. Mean Corpuscular Hemoglobin (MCH) for Part 1a | Blood samples were collected for the assessment of hematology parameter namely blood Ery. MCH for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. Mean Corpuscular Volume (MCV) for Part 1a | Blood samples were collected for the assessment of hematology parameter namely blood Ery. MCV for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. for Part 1a | Blood samples were collected for the assessment of hematology parameter namely blood Ery. for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Hematocrit for Part 1a | Blood samples were collected for the assessment of hematology parameter namely blood hematocrit for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part 1a | Single vital signs were measured in semi-supine position after 5 minutes rest and included SBP, DBP. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Vital Sign Parameter Heart Rate for Part 1a | Single vital signs were measured in semi-supine position after 5 minutes rest and included heart rate. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Electrocardiogram (ECG) Parameter Heart Rate for Part 1a | A 12 lead ECG was measured in semi-supine position after 5 minutes rest using an ECG machine that automatically calculated the heart rate. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Change From Baseline in ECG Parameters PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB) and Corrected QT Interval Using Fridericia's Formula (QTcF) for Part 1a | A 12 lead ECG was measured in semi-supine position after 5 minutes rest using an ECG machine that measured PR interval, QRS duration, QT interval, QTcB and QTcF for Part 1a. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). | Baseline and up to 14 days | |
| Secondary | Number of Participants With Abnormal Values on Urinalysis by Dipstick Analysis Part 1a | Urinalysis parameters assessed were urine ketones, urine glucose, urine occult blood, urine pH, urine specific gravity and urine protein. In this dipstick test, the level of ketones, glucose, occult blood, pH, specific gravity and protein in urine samples was recorded as negative trace, 1+, 3+, 5+, 6+, 7+ and 8+ (the plus sign increases with a higher level of ketones, occult blood, pH or specific gravity in the urine: 1+=slightly positive, 3+ to 5+=positive, 6+ and above=high positive). Urine samples were collected for the measurement of urinalysis parameters by dipstick method up-to follow-up (5 to 7 days post last dose) in Part 1a. Only categories with significant values have been presented. | Up to 14 days | |
| Secondary | Number of Participants With AEs and SAEs for Part 1b | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Glucose, Serum Calcium, Serum Carbon Dioxide, Serum Chloride, Serum Potassium, Serum Sodium and Serum Urea Nitrogen for Part 1b | Blood samples were collected for the assessment of chemistry parameters namely serum glucose, serum calcium, serum carbon dioxide, serum chloride, serum potassium, serum sodium and serum urea nitrogen for Part 1b. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum ALT, Serum AP, Serum AST and Serum CK for Part 1b | Blood samples were collected for the assessment of chemistry parameters namely serum ALT, serum AP, serum AST and serum CK for Part 1b. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Albumin and Serum Protein for Part 1b | Blood samples were collected for the assessment of chemistry parameters namely serum albuim and serum protein for Part 1b. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Bilirubin, Serum Creatinine and Serum Direct Bilirubin in Part 1b | Blood samples were collected for the assessment of chemistry parameters namely serum ALT, serum AP, serum AST and serum CK for Part 1b. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameters Blood Basophils, Blood Eosinophils, Blood Leukocytes, Blood Lymphocytes, Blood Monocytes, Blood Neutrophils and Blood Platelets for Part 1b | Blood samples were collected for the assessment of hematology parameters namely blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils and blood platelets for Part 1b. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameters Blood Ery. MCHC and Blood Hemoglobin for Part 1b | Blood samples were collected for the assessment of hematology parameters namely blood Ery. MCHC and blood hemoglobin for Part 1b. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. MCH for Part 1b | Blood samples were collected for the assessment of hematology parameter namely blood Ery. MCH for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. MCV for Part 1b | Blood samples were collected for the assessment of hematology parameter namely blood Ery. MCV for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. for Part 1b | Blood samples were collected for the assessment of hematology parameter namely blood Ery. for Part 1b. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Hematocrit for Part 1b | Blood samples were collected for the assessment of hematology parameter namely blood hematocrit for Part 1b. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Vital Sign Parameters SBP and DBP for Part 1b | Single vital signs were measured in semi-supine position after 5 minutes rest and included SBP, DBP. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Vital Sign Parameter Heart Rate for Part 1b | Single vital signs were measured in semi-supine position after 5 minutes rest and included heart rate. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in ECG Parameter Heart Rate for Part 1b | A 12 lead ECG was measured in semi-supine position after 5 minutes rest using an ECG machine that automatically calculated the heart rate. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in ECG Parameters PR Interval, QRS Duration, QT Interval, QTcB and QTcF for Part 1b | A 12 lead ECG was measured in semi-supine position after 5 minutes rest using an ECG machine that measured PR interval, QRS duration, QT interval, QTcB and QTcF for Part 1b. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Baseline and up to 11 days | |
| Secondary | Number of Participants With Abnormal Values on Urinalysis by Dipstick Analysis Part 1b | Urinalysis parameters assessed were urine ketones, urine glucose, urine occult blood, urine pH, urine specific gravity and urine protein. In this dipstick test, the level of ketones, glucose, occult blood, pH, specific gravity and protein in urine samples was recorded as negative trace, 1+, 3+, 5+, 6+, 7+ and 8+ (the plus sign increases with a higher level of ketones, occult blood, pH or specific gravity in the urine: 1+=slightly positive, 3+ to 5+=positive, 6+ and above=high positive). Since the relative bio-availability of the RC tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted. | Up to 11 days | |
| Secondary | Number of Participants With Non-serious AEs and SAEs for Part 2 | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. | Up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Glucose, Serum Calcium, Serum Carbon Dioxide, Serum Chloride, Serum Potassium, Serum Sodium and Serum Urea Nitrogen in Part 2 | Blood samples were collected for the assessment of chemistry parameters namely serum glucose, serum calcium, serum carbon dioxide, serum chloride, serum potassium, serum sodium and serum urea nitrogen for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum ALT, Serum AP, Serum AST and Serum CK in Part 2 | Blood samples were collected for the assessment of chemistry parameters namely serum ALT, serum AP, serum AST and serum CK for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Albumin and Serum Protein for Part 2 | Blood samples were collected for the assessment of chemistry parameters namely serum albumin and serum protein for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose-visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Bilirubin, Serum Creatinine and Serum Direct Bilirubin for Part 2 | Blood samples were collected for the assessment of chemistry parameters namely serum bilirubin, serum creatinine and serum direct bilirubin for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameter Serum Estradiol for Part 2 | Blood samples were collected for the assessment of chemistry parameter namely serum estradiol for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the indicated time point were analyzed. NA indicates standard deviation was not calculated as a single participant was analyzed. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameters Blood Basophils, Blood Eosinophils, Blood Leukocytes, Blood Lymphocytes, Blood Monocytes, Blood Neutrophils and Blood Platelets for Part 2 | Blood samples were collected for the assessment of hematology parameters namely blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils and blood platelets for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameters Ery. MCHC and Blood Hemoglobin for Part 2 | Blood samples were collected for the assessment of hematology parameters namely blood Ery. MCHC and blood hemoglobin for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. MCH for Part 2 | Blood samples were collected for the assessment of hematology parameter namely blood Ery. MCH for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. MCV for Part 2 | Blood samples were collected for the assessment of hematology parameter namely blood Ery. MCV for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. for Part 2 | Blood samples were collected for the assessment of hematology parameter namely blood Ery. for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Hematocrit for Part 2 | Blood samples were collected for the assessment of hematology parameter namely blood hematocrit for Part 2. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Vital Sign Parameters SBP and DBP for Part 2 | Single vital signs were measured in semi-supine position after 5 minutes rest and included SBP, DBP. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in Vital Sign Parameter Heart Rate for Part 2 | Single vital signs were measured in semi-supine position after 5 minutes rest and included heart rate. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in ECG Parameter Heart Rate for Part 2 | A 12 lead ECG was measured in semi-supine position after 5 minutes rest using an ECG machine that automatically calculated the heart rate. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Change From Baseline in ECG Parameters PR Interval, QRS Duration, QT Interval, QTcB and QTcF for Part 2 | A 12 lead ECG was measured in semi-supine position after 5 minutes rest using an ECG machine that measured PR interval, QRS duration, QT interval, QTcB and QTcF for Part 2. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. NA indicates participants crossed-over as follow-up visit occurred after Period 2. | Baseline and up to 11 days | |
| Secondary | Number of Participants With Abnormal Values on Urinalysis by Dipstick Analysis Part 2 | Urinalysis parameters assessed were urine ketones, urine glucose, urine occult blood, urine pH, urine specific gravity and urine protein. In this dipstick test, the level of ketones, glucose, occult blood, pH, specific gravity and protein in urine samples was recorded as negative trace, 1+, 3+, 4+ 5+, 6+, 7+ and 8+ (the plus sign increases with a higher level of ketones, occult blood, pH or specific gravity in the urine: 1+=slightly positive, 3+ to 5+=positive, 6+ and above=high positive). Urine samples were collected for the measurement of urinalysis parameters by dipstick method up-to follow-up (5 to 7 days post last dose) in Part 2. Only categories with significant values have been presented. | Baseline and up to 11 days | |
| Secondary | Number of Participants With Non-serious AEs and SAEs for Part 3 | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. | Up to 14 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Glucose, Serum Calcium, Serum Carbon Dioxide, Serum Chloride, Serum Potassium, Serum Sodium and Serum Urea Nitrogen for Part 3 | Blood samples were collected for the assessment of chemistry parameters namely serum glucose, serum calcium, serum carbon dioxide, serum chloride, serum potassium, serum sodium and serum urea nitrogen for Part 3. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum ALT, Serum AP, Serum AST and Serum CK for Part 3 | Blood samples were collected for the assessment of chemistry parameters namely serum ALT, serum AP, serum AST and serum CK for Part 3. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Albumin and Serum Protein for Part 3 | Blood samples were collected for the assessment of chemistry parameters namely serum albumin and serum protein for Part 3. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Clinical Chemistry Parameters Serum Bilirubin and Serum Creatinine for Part 3 | Blood samples were collected for the assessment of chemistry parameters namely serum bilirubin and serum creatinine for Part 3. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameters Blood Basophils, Blood Eosinophils, Blood Leukocytes, Blood Lymphocytes, Blood Monocytes, Blood Neutrophils and Blood Platelets for Part 3 | Blood samples were collected for the assessment of hematology parameters namely blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils and blood platelets for Part 3. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameters Blood Ery. MCHC and Blood Hemoglobin for Part 3 | Blood samples were collected for the assessment of hematology parameters namely blood Ery. MCHC and blood hemoglobin for Part 3. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. MCH for Part 3 | Blood samples were collected for the assessment of hematology parameter namely blood Ery. MCH for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. Mean Corpuscular Volume (MCV) for Part 3 | Blood samples were collected for the assessment of hematology parameter namely blood Ery. MCV for Part 3. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Ery. for Part 3 | Blood samples were collected for the assessment of hematology parameter namely blood Ery. for Part 1a. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Hematology Parameter Blood Hematocrit for Part 3 | Blood samples were collected for the assessment of hematology parameter namely blood hematocrit for Part 3. Baseline was defined as assessments performed on Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Vital Sign Parameters SBP and DBP for Part 3 | Single vital signs were measured in semi-supine position after 5 minutes rest and included SBP, DBP. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in Vital Sign Parameter Heart Rate for Part 3 | Single vital signs were measured in semi-supine position after 5 minutes rest and included heart rate. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in ECG Parameter Heart Rate for Part 3 | A 12 lead ECG was measured in semi-supine position after 5 minutes rest using an ECG machine that automatically calculated the heart rate. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Change From Baseline in ECG Parameters PR Interval, QRS Duration, QT Interval, QTcB and QTcF for Part 3 | A 12 lead ECG was measured in semi-supine position after 5 minutes rest using an ECG machine that measured PR interval, QRS duration, QT interval, QTcB and QTcF for Part 3. Baseline was defined as assessments performed on Day 1 (pre-dose). Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Only those participants with data available at the specified time were analyzed (represented by n=x in the category titles). Data points with null value for participants analyzed indicate data not collected for respective category and treatment arm. | Baseline and up to 14 days | |
| Secondary | Number of Participants With Abnormal Values on Urinalysis by Dipstick Analysis Part 3 | Urinalysis parameters assessed were urine ketones, urine glucose, urine occult blood, urine pH, urine specific gravity and urine protein. In this dipstick test, the level of ketones, glucose, occult blood, pH, specific gravity and protein in urine samples was recorded as negative trace, 1+, 3+, 5+, 6+, 7+ and 8+ (the plus sign increases with a higher level of ketones, occult blood, pH or specific gravity in the urine: 1+=slightly positive, 3+ to 5+=positive, 6+ and above=high positive). Urine samples were collected for the measurement of urinalysis parameters by dipstick method up-to follow-up (5 to 7 days post last dose) in Part 3. Only categories with significant values have been presented. | Up to 14 days |
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