Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03393208
Other study ID # MS200084_0009
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date January 10, 2018
Est. completion date January 29, 2018

Study information

Verified date April 2019
Source Merck KGaA, Darmstadt, Germany
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The study will assess the bioequivalence between single doses of glucophage immediate release (GIR) test tablets and GIR reference tablets under fed and fasted state in healthy subjects.


Recruitment information / eligibility

Status Completed
Enrollment 44
Est. completion date January 29, 2018
Est. primary completion date January 29, 2018
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria:

- Participants had given written informed consent before any trial-related activities

- Chinese male and female participants (at least 1/4 of each gender per trial group)

- Aged between 18 and 55 years, inclusive

- Weighed: 50 to 80 kilogram (kg); Body mass index (BMI): 18 to 30 kg per meter square

- Nonsmoker since at least 3 months

- Good physical and mental health status, determined on the basis of the medical history and a physical examination

- All values for biochemistry and hematology tests of blood and urine within the normal range or showied no clinically relevant deviation as judged by the Investigator

- Electrocardiogram recording (12-lead ECG) without signs of clinically relevant pathology was judged by the Investigator

- Vital signs (blood pressure, pulse, body temperature, and respiration) in sitting position within the normal range or showing no clinically relevant deviation was judged by the Investigator

- All women of childbearing potential (WOCBP) who were not nursing, were not pregnant, and were using highly effective methods of birth control

- Negative screen for alcohol and drugs of abuse (cannabis, benzodiazepines, barbiturates, opiates, cocaine, and methyl amphetamine) were screened at and on admission

- Negative screen for hepatitis A virus (HAV) antibodies, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, and Treponema pallidum (TP) antibodies

Exclusion Criteria:

- Participation in a clinical trial within 90 days prior to first drug administration

- Blood donation (equal or more than 500 milliliter [mL]) or significant blood loss within 90 days prior to first drug administration

- Any surgical or medical condition, including findings in the medical history or in the pretrial assessments, or any other significant disease, that in the opinion of the Investigator, constitutes a risk or a contraindication for the participation of the participant in the trial or that could interfere with the trial objectives, conducted or evaluated

- History of surgery of the gastrointestinal tract which could influence the gastrointestinal absorption and/or motility according to the Investigator's opinion

- History or presence of relevant liver diseases or hepatic dysfunction Allergy: ascertained or presumptive hypersensitivity to the active drug substance and/or formulations' ingredients; history of anaphylaxis to drugs or allergic reactions in general, which the Investigator considered affectted the outcome of the trial

- Receipt of any prescription or nonprescription medication within 2 weeks before the first IMP administration, including multivitamins and herbal products (example, St John's Wort, or traditional Chinese medicines), except paracetamol

- Renal failure or renal dysfunction (creatinine clearance < 80 mL/minute) as assessed by using the estimated measure with the Modification of Diet in Renal Disease (MDRD) equation

- Known lack of participant compliance or inability to communicate or cooperate with the Investigator (example, language problem and poor mental status)

- Nonacceptance of trial high-fat breakfast (example, vegetarians, vegans, and participants followed special diets)

- Consumption of large quantities of methyl xanthine-containing beverages (> 5 cups of coffee/day or equivalent)

- Consumption of grapefruit, cranberry or juices of these fruits, from 14 days prior to drug administration until collection of the last pharmacokinetic sample in Period 2

- Any contraindication to Glucophage

- Abnormal and clinically significant chest X-ray finding at screening

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Test GIR
Participants received 500 milligrams (mg) test GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).
Reference GIR
Participants received 500 mg reference GIR in fasting or fed state on either Day 1 (Treatment Period 1) or Day 8 (Treatment Period 2).

Locations

Country Name City State
China Xuanwu Hospital Beijing

Sponsors (1)

Lead Sponsor Collaborator
Merck KGaA, Darmstadt, Germany

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Metformin (GIR Tablet Active Ingredient) Area under the plasma concentration vs time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was to be calculated according to the mixed log-linear trapezoidal rule. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Primary Maximum Observed Plasma Concentration (Cmax) of Metformin (GIR Tablet Active Ingredient) Pharmacokinetic (PK) parameter Cmax was obtained directly from the concentration versus time curve. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Time to Reach Maximum Plasma Concentration of Metformin (GIR Tablet Active Ingredient) Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Apparent Terminal Half-Life (t1/2) of Metformin (GIR Tablet Active Ingredient) Terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by ?z. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Area Under the Plasma Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Metformin (GIR Tablet Active Ingredient) AUC0-inf was calculated by combining AUC0-t and AUCextra. AUC extra represents an extrapolated value obtained by Clast/ ?z, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLQ) and ?z is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Area Under the Plasma Concentration-Time Curve From Time Tlast Extrapolated to Infinity (AUCextra) of Metformin (GIR Tablet Active Ingredient) AUCextra% was defined as area under the curve from time tlast extrapolated to infinity as percentage of AUC 0-infinity. Here, tlast is the last sampling time at which the concentration is at or above the lower limit of quantification. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Elimination Rate Constant (?z) of Metformin (GIR Tablet Active Ingredient) ?z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Total Body Clearance (CL/f) of Metformin (GIR Tablet Active Ingredient) Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Apparent Volume of Distribution at After Extravascular Administration (Vz/f) of Metformin (GIR Tablet Active Ingredient) Vz/f is defined as the distribution of a study drug between plasma and the rest of the body after oral dosing. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Apparent Volume of Distribution at Steady-State After Extravascular Administration (Vss/f) of Metformin Vss/F was derived from concentration versus time data for all participants. Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14 hours post-dose on Day 1; 24 and 36 hours post-dose on Day 2; 48 hours post-dose on Day 3
Secondary Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. TEAEs included both Serious TEAEs and non-serious TEAEs. Baseline up to Day 15
Secondary Number of Participants With Clinically Significant Abnormalities in Vital Signs, Laboratory Parameters, Physical Examination Findings and 12-lead Electrocardiogram (ECG) Findings The laboratory measurements included hematology, blood chemistry and urinalysis. Vital sign assessment included blood pressure, pulse rate and body temperature. ECG parameters included heart rate, PR, QRS,QT, RR, QTcB and QTcF Here, we are reporting number of participants with clinically significant abnormalities in Vital signs, laboratory parameters, physical findings and ECG findings. Baseline up to Day 15
See also
  Status Clinical Trial Phase
Recruiting NCT06052553 - A Study of TopSpin360 Training Device N/A
Completed NCT05511077 - Biomarkers of Oat Product Intake: The BiOAT Marker Study N/A
Recruiting NCT04632485 - Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging
Completed NCT05931237 - Cranberry Flavan-3-ols Consumption and Gut Microbiota in Healthy Adults N/A
Terminated NCT04556032 - Effects of Ergothioneine on Cognition, Mood, and Sleep in Healthy Adult Men and Women N/A
Completed NCT04527718 - Study of the Safety, Tolerability and Pharmacokinetics of 611 in Adult Healthy Volunteers Phase 1
Completed NCT04065295 - A Study to Test How Well Healthy Men Tolerate Different Doses of BI 1356225 Phase 1
Completed NCT04107441 - AX-8 Drug Safety, Tolerability and Plasma Levels in Healthy Subjects Phase 1
Completed NCT04998695 - Health Effects of Consuming Olive Pomace Oil N/A
Completed NCT01442831 - Evaluate the Absorption, Metabolism, And Excretion Of Orally Administered [14C] TR 701 In Healthy Adult Male Subjects Phase 1
Terminated NCT05934942 - A Study in Healthy Women to Test Whether BI 1358894 Influences the Amount of a Contraceptive in the Blood Phase 1
Recruiting NCT05525845 - Studying the Hedonic and Homeostatic Regulation of Food Intake Using Functional MRI N/A
Completed NCT05515328 - A Study in Healthy Men to Test How BI 685509 is Processed in the Body Phase 1
Completed NCT05030857 - Drug-drug Interaction and Food-effect Study With GLPG4716 and Midazolam in Healthy Subjects Phase 1
Completed NCT04967157 - Cognitive Effects of Citicoline on Attention in Healthy Men and Women N/A
Recruiting NCT04714294 - Evaluate the Safety, Tolerability and Pharmacokinetics Characteristics of HPP737 in Healthy Volunteers Phase 1
Recruiting NCT04494269 - A Study to Evaluate Pharmacokinetics and Safety of Tegoprazan in Subjects With Hepatic Impairment and Healthy Controls Phase 1
Completed NCT04539756 - Writing Activities and Emotions N/A
Recruiting NCT04098510 - Concentration of MitoQ in Human Skeletal Muscle N/A
Completed NCT03308110 - Bioavailability and Food Effect Study of Two Formulations of PF-06650833 Phase 1