A Food-effect Study of the Pediatric Dispersible Tablet Formulations of TRIUMEQ® and DOVATO® in Healthy Adult Participants

HIV Infections Clinical Trial

Official title:

A Randomized, 2-Cohort, 2-Period, Single Dose, Crossover Clinical Study to Assess the Effect of Food on the Pediatric Dispersible Tablet Formulations of TRIUMEQ (Dolutegravir/Abacavir/Lamivudine) and DOVATO (Dolutegravir/Lamivudine) in Healthy Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04827134
• Other study ID #: 216149
• Status: Completed
• Phase: Phase 1
• Start date: May 7, 2021
• Est. completion date: July 23, 2021

Study information

• Verified date: June 2022
• Source: ViiV Healthcare
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the effect of food on the pharmacokinetics (PK) of pediatric formulations of TRIUMEQ (dolutegravir [DTG] 5 milligrams [mg]/abacavir [ABC] 60 mg/lamivudine [3TC] 30 mg) dispersible tablets and DOVATO (DTG 5 mg/3TC 30 mg) dispersible tablets in healthy adult participants. Additionally, safety and tolerability of these formulations will also be assessed. TRIUMEQ and DOVATO are registered trademarks of GlaxoSmithKline group of companies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: July 23, 2021
• Est. primary completion date: July 23, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
• Participants who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
• Body weight >=50.0 kilograms (kg) (110 pounds [lbs.]) for males and >=45 kg (99 lbs.) for females and body mass index within the range 18.5 to 31.0 kilogram per meter square (kg/m^2, inclusive).
• A male participant is eligible to participate if they agree to use contraceptive methods.
• A female participant is eligible to participate if she is not pregnant (, not lactating or breastfeeding, and at least 1 of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a non-hormonal contraceptive method that is highly effective
• Capable of giving signed informed consent
• Documentation that the participant is negative for the human leukocyte antigen (HLA) B*5701 allele.

Exclusion Criteria:

• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
• A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study intervention.
• QT interval corrected for heart rate according to Fridericia's formula (QTcF) >450 milliseconds (msec).
• A participant with known or suspected active coronavirus disease (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment.
• Presence of hepatitis B surface antigen at screening or within 3 months prior to starting study intervention.
• Positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention AND positive on reflex to hepatitis C ribonucleic acid (RNA).
• Positive human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at screening.
• Alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
• Bilirubin >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility.
• Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
• Any Grade 2 to 4 laboratory abnormality at screening, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT (described above), will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility.
• A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at screening or before the first dose of study intervention.
• Unable to refrain from the use of prescription or non-prescription drugs including vitamins, herbal and dietary supplements (including St. John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention and for the duration of the study until completion of the follow-up visit, unless, in the opinion of the investigator and ViiV Healthcare (VH)/GlaxoSmithKline medical monitor, the medication will not interfere with the study procedures or compromise participant safety.
• Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
• Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to Day 1 of Period 1 in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the study intervention (whichever is longer).
• Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 60 days.
• Estimated serum creatinine clearance (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) <90 milliliter per minute (mL/min).
• History of regular alcohol consumption within 6 months of the study, defined as an average weekly intake of >14 units for males or >7 drinks for females.
• Unable to refrain from tobacco or nicotine-containing products within 1 month prior to screening.
• History of sensitivity, prior intolerance or hypersensitivity to any of the study interventions, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• TRIUMEQ
TRIUMEQ will be available as fixed dose combination (FDC) dispersible tablets to be administered orally as a dispersion.
• DOVATO
DOVATO will be available as FDC dispersible tablets to be administered orally as a dispersion.

Locations

Country	Name	City	State
United States	GSK Investigational Site	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
ViiV Healthcare

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohort 1: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC [0-inf]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Primary	Cohort 1: AUC From Time Zero to Time of Last Observed Quantifiable Concentration (AUC [0-t]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Primary	Cohort 1: Maximum Observed Concentration (Cmax) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Primary	Cohort 2: AUC (0-inf) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Primary	Cohort 2: AUC (0-t) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Primary	Cohort 2: Cmax of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 1: Lag Time for Absorption (Tlag) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 1: Terminal Elimination Phase Half-life (t1/2) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 1: AUC From Time Zero to 24 Hours (AUC[0-24]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12 and 24 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 1: Last Quantifiable Concentration (Ct) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 1: Concentration at 24 Hours Post-dose (C24) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	24 hours post dose in treatment periods 1 and 2
Secondary	Cohort 1: Time of Maximum Observed Concentration (Tmax) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 2: Tlag of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 2: t1/2 of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 2: AUC(0-24) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12 and 24 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 2: Ct of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Cohort 2: C24 of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	24 hours post dose in treatment periods 1 and 2
Secondary	Cohort 2: Tmax of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions	Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment.	Up to 23 days
Secondary	Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and Neutrophil	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count	Blood samples were collected to analyze the hematology parameter: RBC count. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Hematology Parameters: Hemoglobin	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Hematology Parameters: Hematocrit	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameter: erythrocytes mean corpuscular Volume. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and Neutrophil	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Hematology Parameters: RBC Count	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameters: RBC count. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Hematology Parameters: Hemoglobin	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Hematology Parameters: Hematocrit	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Hematology Parameters: Erythrocytes Mean Corpuscular Volume	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameter: erythrocytes mean corpuscular Volume. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Amino Transferase (AST)	Blood samples were collected to analyze the clinical chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the clinical chemistry parameters: calcium, glucose, potassium, sodium and BUN. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin and Total Bilirubin	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the clinical chemistry parameters: creatinine, direct bilirubin and total bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Clinical Chemistry Parameters: Creatine Kinase	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the clinical chemistry parameters: creatine kinase. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Clinical Chemistry Parameters: Albumin and Total Protein	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the clinical chemistry parameters: albumin and total protein. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Clinical Chemistry Parameters: ALT, ALP and AST	Blood samples were collected to analyze the clinical chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and BUN	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the clinical chemistry parameters: calcium, glucose, potassium, sodium and BUN. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin and Total Bilirubin	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the clinical chemistry parameters: creatinine, direct bilirubin and total bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Clinical Chemistry Parameters: Creatine Kinase	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the clinical chemistry parameters: creatine kinase. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Clinical Chemistry Parameters: Albumin and Total Protein	Blood samples were collected at Baseline and at Day 4 post dose of each period to analyze the clinical chemistry parameters: albumin and total protein. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Urinalysis Parameter: Specific Gravity	Urine samples were collected at Baseline and at Day 4 post dose of each period to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) by Dipstick	Urine samples were collected at Baseline and at Day 4 post dose of each period to analyze the urinalysis parameter: pH by dipstick. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Urinalysis Parameter: Specific Gravity	Urine samples were collected at Baseline and at Day 4 post dose of each period to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Urinalysis Parameter: Potential of Hydrogen (pH) by Dipstick	Urine samples were collected at Baseline and at Day 4 post dose of each period to analyze the urinalysis parameter: pH by dipstick. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Number of Participants With Abnormal Values on Urinalysis by Dipstick	Urine samples were collected at indicated time points to analyze parameters including glucose, protein, blood, and ketones by dipstick. The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters can be read as Negative, Trace, 1+ (low concentrations present), 2+ (moderate concentrations present), 3+ (high concentrations present) and 4+ (very high concentrations present) indicating proportional concentrations in the urine sample.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and Corrected QT Interval According to Fridericia's Formula (QTcF)	Single 12-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF	Single 12-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Vital Signs Measurements: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	SBP and DBP were measured in the supine or semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Vital Signs Measurements: SBP and DBP	SBP and DBP were measured in the supine or semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4
Secondary	Change From Baseline in Vital Signs Measurements: Pulse Rate	Pulse rate were measured in the supine or semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and Day 4
Secondary	Absolute Values of Vital Signs Measurements: Pulse Rate	Pulse rate were measured in the supine or semi-supine position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits.	Baseline (Day -1) and Day 4