To Assess the Relative Bioavailability (BA) of TRIUMEQ® and Dolutegravir and Lamivudine (DTG/3TC) Pediatric Dispersible Tablet Formulations in Healthy Volunteers

Study Overview
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Brief Summary
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This is a 2-part, single-dose, open label, randomized 3-way cross-over study to compare BA of pediatric study drugs TRIUMEQ and (DTG/3TC) in healthy volunteers under fasted conditions. Study will be conducted in 2-parts. Each part 1 and part 2 will comprise of 3-treatment periods (TP) where Part 1, will assess BA, of pediatric TRIUMEQ dispersible tablets with an adult TRIUMEQ conventional tablet formulation and Part 2, will assess BA, of pediatric DTG/3TC dispersible tablets with adult DTG and 3TC conventional tablets formulation. Total duration of study is 9-weeks and will be conducted in approximately 36 subjects. The 2-parts, may be run in parallel as they are independent of each other. TRIUMEQ is a registered trademark of GlaxoSmithKline group of companies.

Official Title
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A 2-Part, Phase I, Single-Dose, 3-Period Crossover Relative Bioavailability Study of a Pediatric TRIUMEQ Dispersible Tablet and Pediatric Dolutegravir and Lamivudine (DTG/3TC) Fixed Dose Combination Dispersible Tablet Formulations as Compared With Adult Tablets in Healthy Volunteers

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Treatment A
* Drug: Treatment B
* Drug: Treatment C
* Drug: Treatment D
* Drug: Treatment E
* Drug: Treatment F


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 18 and 65 years of age, inclusive, at the time of signing the informed consent. Healthy subjects as determined by the investigator or medically qualified designee based on a medical evaluation, including medical history, physical examination, laboratory tests, and cardiac evaluation (history and ECG). Body weight >=50 kilogram (kg) for males and >=45 kg for females and body mass index (BMI) within the range 18.5 - 31.0 kilogram per square meter (kg/m^2) (inclusive). Male and female subjects where the male subjects must agree to use contraception during the TP and for at least 2 weeks plus an additional 90 days (a spermatogenesis cycle) after the last dose of study treatment and refrain from donating sperm during this period. For the female subjects, female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and at least 1 of the following conditions applies: Female with non-reproductive potential, defined as Premenopausal females with one of the following like documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, documented hysterectomy, documented bilateral oophorectomy, the 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; Females with reproductive potential and agrees to follow one of the options for avoiding pregnancy in females of reproductive potential, from 30 days prior to the first dose of study medication and until 2 weeks after dosing with study medication and completion of the follow-up visit; the investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception; All female subjects participating in the study should be counselled on safer sexual practices including the use and benefit/risk of effective barrier methods (e.g., male condom) and on the risk of human immune virus (HIV) transmission to an uninfected partner. Subjects capable of giving signed informed consent. For participation in Part 1, documentation that the subject is negative for the human leukocyte antigen (HLA)-B*5701 allele. Exclusion Criteria: The medical conditions included where ALT and bilirubin >1.5 × upper limit of normal (ULN) (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin < =35%). Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination) where the heart rate for the male subjects be <45 and >100 beats per minute (bpm) and that for females be < 50 and > 100 bpm; the PR interval for both be < 120 and > 220 millisecond (msec); the QRS interval be < 70 and > 120 msec and the corrected Q-T interval (QTc) obtained using the Fridericia's formula (QTcF) be >450 msec ; ECG with 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 [2nd degree or higher], Wolf-Parkinson-White syndrome); Sinus pauses > 3 seconds; any significant arrhythmia which, in the opinion of the principal investigator or ViiV/GlaxoSmithKline (GSK) medical monitor, will interfere with the safety of the individual subject; non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats). Subjects with use of prior or concomitant therapy who are unable to refrain from the use of prescription (e.g., dofetilide) 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 medication, unless in the opinion of the Investigator and ViiV Healthcare Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. History of regular alcohol consumption within 6 months of the study, defined as an average weekly intake of >14 drinks for males or > 7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine, or 1.5 ounces (45 mL) of 80 proof distilled spirits. Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 1 month prior to screening. Contraindications like 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. The subject has participated in a clinical trial and has received an investigational product (IP) 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 IP (whichever is longer). The subject has participated in a clinical trial and has received an IP 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 IP (whichever is longer). Creatinine clearance (CrCL) < 90 mL per minute. Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. A positive pre-study drug/alcohol/cotinine screen. A positive test for HIV antibody. Where participation in the study would result in donation of blood or blood product in excess of 500 mL within 60 days. Exposure to more than four new chemical entities within 12 months prior to the first dosing day.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: 2-part study with 3-TPs each. Part 1, compares relative BA of TRIUMEQ dispersible tablets for pediatric populations (DTG, 5 milligram [mg]/abacavir [ABC] 60 mg/3TC 30 mg), when administered as direct-to-mouth and when dispersed into purified water, with adult TRIUMEQ conventional tablet (DTG 50 mg/ABC 600 mg/3TC 300 mg), administered as direct-to-mouth (reference). Additionally, part 2 will compare relative BA of DTG/3TC (DTG 5 mg/3TC 30 mg), dispersible tablets for pediatric populations, when administered as direct-to mouth and when dispersed into purified water, with adult DTG (50 mg) and 3TC (300 mg) conventional tablets, when administered as direct-to-mouth (reference). Each TP, in Part 1 and 2 will have, wash-out period of 7-days (with minus 4 hours) between each single dose, for flexible dosing. During TPs, subjects will be admitted, to clinic on Day-1, following completion of last study procedure on Day 4, post which follow-up visit conducted, 7 to 10 days after last dose.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Subjects with treatment sequence ABC<br>The subjects in Part 1 of the study, will receive a single dose of treatment A= adult TRIUMEQ (DTG 50 mg/ABC 600 mg/3TC 300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment B=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment C=Pediatric TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment A<br>* TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.<br>Drug: Treatment B<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets<br>Drug: Treatment C<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence BCA<br>The subjects in Part 1 of the study, will receive treatment B in TP1, treatment C in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment A<br>* TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.<br>Drug: Treatment B<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets<br>Drug: Treatment C<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence CAB<br>The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment A in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment A<br>* TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.<br>Drug: Treatment B<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets<br>Drug: Treatment C<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence ACB<br>The subjects in Part 1 of the study will receive, treatment A in TP1, treatment C in TP2 and treatment B in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment A<br>* TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.<br>Drug: Treatment B<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets<br>Drug: Treatment C<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence BAC<br>The subjects in Part 1 of the study will receive a single dose each of, treatment B in TP1, treatment A in TP2 and treatment C in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment A<br>* TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.<br>Drug: Treatment B<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets<br>Drug: Treatment C<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence CBA<br>The subjects in Part 1 of the study will receive a single dose each of, treatment C in TP1, treatment B in TP2 and treatment A in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment A<br>* TRIUMEQ (Adult) administered as a, single dose, fixed dose combination (FDC) tablet - DTG 50 mg/ABC 600 mg/3TC 300 mg as 1 conventional tablet, orally as direct-to-mouth.<br>Drug: Treatment B<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets<br>Drug: Treatment C<br>* TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence DEF<br>The subjects in Part 2 of the study, will receive a single dose of treatment D= Adult DTG (50 mg, 1 conventional tablet) and adult 3TC (300 mg, 1 conventional tablet) administered as direct-to-mouth, in TP1; treatment E= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as a dispersion and taken immediately in TP2; and treatment F= Pediatric DTG/3TC (DTG 5 mg/3TC 30 mg, 10 dispersible tablets) administered as direct-to-mouth in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment D<br>* DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and 1 tablet 3TC (300 mg), orally as direct-to-mouth.<br>Drug: Treatment E<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.<br>Drug: Treatment F<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence EFD<br>The subjects in Part 2 of the study, will receive a single dose respectively of treatment E in TP1, treatment F in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment D<br>* DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and 1 tablet 3TC (300 mg), orally as direct-to-mouth.<br>Drug: Treatment E<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.<br>Drug: Treatment F<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence FDE<br>The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment D in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment D<br>* DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and 1 tablet 3TC (300 mg), orally as direct-to-mouth.<br>Drug: Treatment E<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.<br>Drug: Treatment F<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence DFE<br>The subjects in Part 2 of the study, will receive a single dose of treatment D in TP1, treatment F in TP2 and treatment E in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment D<br>* DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and 1 tablet 3TC (300 mg), orally as direct-to-mouth.<br>Drug: Treatment E<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.<br>Drug: Treatment F<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence EDF<br>The subjects in Part 2 of the study, will receive a single dose of treatment E in TP1, treatment D in TP2 and treatment F in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment D<br>* DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and 1 tablet 3TC (300 mg), orally as direct-to-mouth.<br>Drug: Treatment E<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as 10 dispersible tablets.<br>Drug: Treatment F<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.<br>|
| Experimental: Subjects with treatment sequence FED<br>The subjects in Part 2 of the study, will receive a single dose of treatment F in TP1, treatment E in TP2 and treatment D in TP3. Each treatment will be followed by a wash-out period of 7-days minus 4 hours. | Drug: Treatment D<br>* DTG and 3TC (Adult), administered as a, single dose, Single dose, 1 tablet DTG (50 mg) and 1 tablet 3TC (300 mg), orally as direct-to-mouth.<br>Drug: Treatment F<br>* DTG and 3TC (Pediatric) administered as a, single dose, FDC tablet single dose, FDC tablet - DTG 5 mg/3TC 30 mg, orally as direct-to-mouth.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Plasma Concentration-time Curve (AUC) From Time of Dose Extrapolated to Infinity (AUC[0-inf]) in Part 1 of DTG | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate pharmacokinetic (PK) parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. PK population comprised of participants in the all participants population (participants who took at least 1 dose of study medication) for whom PK sample was obtained and who had evaluable PK assay results. Statistics has been presented on geometric least square (LS) means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC From Time of Dose to Last Measurable Concentration (AUC[0-t]) in Part 1 of DTG | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose,15 and 30 minutes,1 ,1.5 ,2 ,2.5 ,3 ,4 ,5 ,6 ,8 ,12 ,16 ,24 ,48 and 72 hours post-dose of each treatment period | 
| Maximum Observed Concentration (Cmax) in Part 1 of DTG in Plasma | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-inf) in Part 1 of ABC | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-t) in Part 1 of ABC | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Cmax in Part 1 of ABC in Plasma | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-inf) in Part 1 of 3TC | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC (0-t) in Part 1 of 3TC | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Cmax in Part 1 of 3TC | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-inf) in Part 2 of DTG in Plasma | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-t) in Part 2 of DTG | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Cmax in Part 2 of DTG in Plasma | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. PK analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-inf) in Part 2 of 3TC | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-t) in Part 2 of 3TC | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Cmax in Part 2 of 3TC | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC From Time of Dose to 24 Hours (AUC[0-24]) of DTG in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Time to Maximum Concentration (Tmax) of DTG in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Time of Last Quantifiable Concentration (Tlast) of DTG in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Apparent Oral Clearance (CL/F) of DTG in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Apparent Volume of Distribution (Vz/F) of DTG in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Observed Concentration at 24 Hours Postdose (C24) of DTG in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Last Observed Quantifiable Concentration (Ct) of DTG in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Terminal Elimination Phase Half-life (t½) of DTG in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Lag Time for Absorption (Tlag) of DTG in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-24) of ABC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Tmax of ABC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Tlast of ABC in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| CL/F of ABC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Vz/F of ABC in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| C24 of ABC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Ct of ABC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| T½ of ABC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of ABC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC(0-24) of 3TC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Tmax of 3TC in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Tlast of 3TC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| CL/F of 3TC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Vz/F of 3TC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| C24 of 3TC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Ct of 3TC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| T½ of 3TC in Plasma in Part 1 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 1. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC (0-24) of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Tmax of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Tlast of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| CL/F of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Vz/F of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| C24 of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Ct of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| T½ of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Tlag of DTG in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of DTG in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| AUC (0-24) of 3TC in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Tmax of 3TC in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Tlast of 3TC in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| CL/F of 3TC in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Vz/F of 3TC in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| C24 of 3TC in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. Statistics has been presented on geometric LS means. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 and 24 hours post-dose of each treatment period | 
| Ct of 3TC in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| T½ of 3TC in Plasma in Part 2 | Blood samples were collected from participants at indicated time points after the administration of study treatment to investigate PK parameters of 3TC in Part 2. Pharmacokinetic analysis was conducted using standard non-compartmental methods. | Pre-dose, 15 and 30 minutes, 1 , 1.5 , 2 , 2.5 , 3 , 4 , 5 , 6 , 8 , 12 , 16 , 24 , 48 and 72 hours post-dose of each treatment period | 
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Part 1 | 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. A 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, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety population comprised of all participants enrolled in the study, who took at least one dose of study treatment. | Up to Day 33 | 
| Number of Participants With AEs and Serious Adverse Events SAEs in Part 2 | 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. A 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, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. | Up to Day 33 | 
| Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea | Blood samples were collected for the analysis of clinical chemistry parameters which included glucose, calcium, potassium, sodium and urea. All participants population included all participants who received at least one dose of study medication. This population corresponded to all participants enrolled. | Day 2 of each treatment period | 
| Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotranferase (AST) and Creatinine Phosphokinase (CPK) | Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CPK. | Day 2 of each treatment period | 
| Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein | Blood samples were collected for the analysis of clinical chemistry parameters including albumin and protein. | Day 2 of each treatment period | 
| Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin | Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin. | Day 2 of each treatment period | 
| Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea | Blood samples were collected for the analysis of clinical chemistry parameters including glucose, calcium, potassium, sodium and urea. | Day 2 of each treatment period | 
| Absolute Values for Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK | Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CPK. | Day 2 of each treatment period | 
| Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein | Blood samples were collected for the analysis of clinical chemistry parameters including albumin and protein. | Day 2 of each treatment period | 
| Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin | Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin. | Day 2 of each treatment period | 
| Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea | Blood samples were collected for the analysis of clinical chemistry parameters including glucose, calcium, potassium, sodium and urea. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: ALT, ALP, AST and CPK | Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CPK. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein | Blood samples were collected for the analysis of clinical chemistry parameters including albumin and protein. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin | Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea | Blood samples were collected for the analysis of clinical chemistry parameters including glucose, calcium, potassium, sodium and urea. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK | Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CPK. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein | Blood samples were collected for the analysis of clinical chemistry parameters including albumin and protein. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin | Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin. Day -1 was defined as Baseline for clinical chemistry parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1 | Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelets in Part 1 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1 | Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 1 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Erythrocytes in Part 1 | Blood samples were collected for the analysis erythrocytes in Part 1 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Hemocrit in Part 1 | Blood samples were collected for the analysis hemocrit in Part 1 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Hemoglobin in Part 1 | Blood samples were collected for the analysis hemoglobin in Part 1 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2 | Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelets in Part 2 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2 | Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 2 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Erythrocyte Mean Corpuscular Volume in Part 2 | Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 2 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Erythrocytes in Part 2 | Blood samples were collected for the analysis erythrocytes in Part 2 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Hemocrit in Part 2 | Blood samples were collected for the analysis hemocrit in Part 2 at indicated time points. | Day 2 of each treatment period | 
| Absolute Values for Hemoglobin in Part 2 | Blood samples were collected for the analysis hemoglobin in Part 2 at indicated time points. | Day 2 of each treatment period | 
| Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1 | Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelets in Part 1 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1 | Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 1 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 1 | Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 1 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Erythrocytes in Part 1 | Blood samples were collected for the analysis erythrocytes in Part 1 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Hemocrit in Part 1 | Blood samples were collected for the analysis hemocrit in Part 1 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Hemoglobin in Part 1 | Blood samples were collected for the analysis hemoglobin in Part 1 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2 | Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelets in Part 2 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2 | Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 2 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 2 | Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 2 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Erythrocytes in Part 2 | Blood samples were collected for the analysis erythrocytes in Part 2 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Hemocrit in Part 2 | Blood samples were collected for the analysis hemocrit in Part 2 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Change From Baseline Values for Hemoglobin in Part 2 | Blood samples were collected for the analysis hemoglobin in Part 2 at indicated time points. Day -1 was defined as Baseline for hematology parameters. Change from Baseline is calculated as the value at specified time point minus the Baseline value. | Baseline (Day -1) and Day 2 | 
| Number of Participants With Abnormal Urinalysis Parameter in Part 1 | The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters can be read as increased, decreased, increase to trace, 1+ and 3+ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented. | Up to Day 33 | 
| Number of Participants With Urine Potential of Hydrogen (pH)-Part 1 | Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). | Up to Day 33 | 
| Number of Participants With Abnormal Urinalysis Parameter in Part 2 | The dipstick test gives results in a semi-quantitative manner and results for urinalysis parameters can be read as increased, decreased, increase to trace, 1+ and 3+ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented. | Up to Day 33 | 
| Number of Participants With Urine Potential of Hydrogen (pH)-Part 2 | Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). | Up to Day 33 | 
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Part 1 | Full 12-lead ECGs were recorded with the participant in a supine position. Absolute QTc Interval: >450, absolute PR Interval: <110 and Absolute QRS Interval: <75 were considered to be potential clinically significant ECG finding. The number of participants with abnormal clinically significant ECG findings are presented. | Baseline (Day -1) | 
| Number of Participants With Abnormal ECG Findings in Part 2 | Full 12-lead ECGs were recorded with the participant in a supine position. Absolute QTc Interval: >450, absolute PR Interval: <110 and Absolute QRS Interval: <75 were considered to be potential clinically significant ECG finding. The number of participants with abnormal clinically significant ECG findings are presented | Baseline (Day -1) | 
| Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Part 1 | Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. | Day 1 at 4 hours post intervention and Day 2 of each treatment period | 
| Absolute Values for Pulse Rate in Part 1 | Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. | Day 1 at 4 hours post intervention and Day 2 of each treatment period | 
| Absolute Values for Temperature in Part 1 | Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. | Day 1 at 4 hours post intervention dose and Day 2 of each treatment period | 
| Absolute Values for SBP and DBP of Part 2 | Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. | Day 1 at 4 hours post intervention dose and Day 2 of each treatment period | 
| Absolute Values for Pulse Rate in Part 2 | Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. | Day 1 at 4 hours post intervention dose and Day 2 of each treatment period | 
| Absolute Values for Temperature in Part 2 | Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. | Day 1 at 4 hours post intervention dose and Day 2 of each treatment period | 
| Change From Baseline in SBP and DBP of Part 1 | Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2 | 
| Change From Baseline in Pulse Rate of Part 1 | Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2 | 
| Change From Baseline in Temperature of Part 1 | Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2 | 
| Change From Baseline in SBP and DBP of Part 2 | Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2 | 
| Change From Baseline in Pulse Rate in Part 2 | Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2 | 
| Change From Baseline in Temperature in Part 2 | Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline value is calculated as the value at the post-dose visit minus the Baseline value. | Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric dispersible tablets, Bioavailability