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

Primary Purpose

HIV Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Treatment A

Treatment B

Treatment C

Treatment D

Treatment E

Treatment F

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Pediatric dispersible tablets, Bioavailability

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm Type

Experimental

Arm Label

Subjects with treatment sequence ABC

Subjects with treatment sequence BCA

Subjects with treatment sequence CAB

Subjects with treatment sequence ACB

Subjects with treatment sequence BAC

Subjects with treatment sequence CBA

Subjects with treatment sequence DEF

Subjects with treatment sequence EFD

Subjects with treatment sequence FDE

Subjects with treatment sequence DFE

Subjects with treatment sequence EDF

Subjects with treatment sequence FED

Arm Description

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

Cmax in Part 1 of ABC in Plasma

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.

AUC (0-t) in Part 1 of 3TC

Cmax in Part 1 of 3TC

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.

AUC(0-t) in Part 2 of DTG

Cmax in Part 2 of DTG in Plasma

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.

AUC(0-t) in Part 2 of 3TC

Cmax in Part 2 of 3TC

Secondary Outcome Measures

AUC From Time of Dose to 24 Hours (AUC[0-24]) of DTG in Part 1

Time to Maximum Concentration (Tmax) of DTG in Plasma in Part 1

Time of Last Quantifiable Concentration (Tlast) of DTG in Part 1

Apparent Oral Clearance (CL/F) of DTG in Plasma in Part 1

Apparent Volume of Distribution (Vz/F) of DTG in Part 1

Observed Concentration at 24 Hours Postdose (C24) of DTG in Plasma in Part 1

Last Observed Quantifiable Concentration (Ct) of DTG in Plasma in Part 1

Terminal Elimination Phase Half-life (t½) of DTG in Plasma in Part 1

Lag Time for Absorption (Tlag) of DTG in Part 1

AUC(0-24) of ABC in Plasma in Part 1

Tmax of ABC in Plasma in Part 1

Tlast of ABC in Part 1

CL/F of ABC in Plasma in Part 1

Vz/F of ABC in Part 1

C24 of ABC in Plasma in Part 1

Ct of ABC in Plasma in Part 1

T½ of ABC in Plasma in Part 1

AUC(0-24) of 3TC in Plasma in Part 1

Tmax of 3TC in Part 1

Tlast of 3TC in Plasma in Part 1

CL/F of 3TC in Plasma in Part 1

Vz/F of 3TC in Plasma in Part 1

C24 of 3TC in Plasma in Part 1

Ct of 3TC in Plasma in Part 1

T½ of 3TC in Plasma in Part 1

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.

Tmax of DTG in Plasma in Part 2

Tlast of DTG in Plasma in Part 2

CL/F of DTG in Plasma in Part 2

Vz/F of DTG in Plasma in Part 2

C24 of DTG in Plasma in Part 2

Ct of DTG in Plasma in Part 2

T½ of DTG in Plasma in Part 2

Tlag of DTG in Plasma in Part 2

AUC (0-24) of 3TC in Plasma in Part 2

Tmax of 3TC in Plasma in Part 2

Tlast of 3TC in Plasma in Part 2

CL/F of 3TC in Plasma in Part 2

Vz/F of 3TC in Plasma in Part 2

C24 of 3TC in Plasma in Part 2

Ct of 3TC in Plasma in Part 2

T½ of 3TC in Plasma in Part 2

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.

Number of Participants With AEs and Serious Adverse Events SAEs in Part 2

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea

Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK

Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein

Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin

Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1

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.

Absolute Values for Erythrocytes in Part 1

Blood samples were collected for the analysis erythrocytes in Part 1 at indicated time points.

Absolute Values for Hemocrit in Part 1

Blood samples were collected for the analysis hemocrit in Part 1 at indicated time points.

Absolute Values for Hemoglobin in Part 1

Blood samples were collected for the analysis hemoglobin in Part 1 at indicated time points.

Absolute Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2

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.

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.

Absolute Values for Erythrocytes in Part 2

Blood samples were collected for the analysis erythrocytes in Part 2 at indicated time points.

Absolute Values for Hemocrit in Part 2

Blood samples were collected for the analysis hemocrit in Part 2 at indicated time points.

Absolute Values for Hemoglobin in Part 2

Blood samples were collected for the analysis hemoglobin in Part 2 at indicated time points.

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.

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.

Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 1

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.

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.

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.

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.

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.

Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 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.

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.

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.

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.

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).

Number of Participants With Abnormal Urinalysis Parameter in Part 2

Number of Participants With Urine Potential of Hydrogen (pH)-Part 2

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.

Number of Participants With Abnormal ECG Findings in Part 2

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.

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.

Absolute Values for Temperature in Part 1

Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

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.

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.

Absolute Values for Temperature in Part 2

Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

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.

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.

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.

Change From Baseline in SBP and DBP of Part 2

Change From Baseline in Pulse Rate in Part 2

Change From Baseline in Temperature in Part 2

Full Information

NCT ID

NCT03441984

First Posted

February 15, 2018

Last Updated

November 20, 2019

Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline, Pharmaceutical Product Development (PPD), Inc

1. Study Identification

Unique Protocol Identification Number

NCT03441984

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

February 26, 2018 (Actual)

Primary Completion Date

April 28, 2018 (Actual)

Study Completion Date

April 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

ViiV Healthcare

Collaborators

GlaxoSmithKline, Pharmaceutical Product Development (PPD), Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV Infections

Keywords

Pediatric dispersible tablets, Bioavailability

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

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)

Masking Description

This is an open-label study in healthy volunteers.

Allocation

Randomized

Enrollment

36 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Subjects with treatment sequence ABC

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence BCA

Arm Type

Experimental

Arm Description

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.

Arm Title

Subjects with treatment sequence CAB

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence ACB

Arm Type

Experimental

Arm Description

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.

Arm Title

Subjects with treatment sequence BAC

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence CBA

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence DEF

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence EFD

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence FDE

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence DFE

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence EDF

Arm Type

Experimental

Arm Description

Arm Title

Subjects with treatment sequence FED

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Treatment A

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Treatment B

Intervention Description

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/ 3TC 30 mg, orally as 10 dispersible tablets

Intervention Type

Drug

Intervention Name(s)

Treatment C

Intervention Description

TRIUMEQ (Pediatric) administered as a, single dose, FDC tablet - DTG 5 mg/ABC 60 mg/3TC 30 mg, orally as direct-to-mouth.

Intervention Type

Drug

Intervention Name(s)

Treatment D

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Treatment E

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Treatment F

Intervention Description

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.

Primary Outcome Measure Information:

Title

Area Under the Plasma Concentration-time Curve (AUC) From Time of Dose Extrapolated to Infinity (AUC[0-inf]) in Part 1 of DTG

Description

Time Frame

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

Title

AUC From Time of Dose to Last Measurable Concentration (AUC[0-t]) in Part 1 of DTG

Description

Time Frame

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

Title

Maximum Observed Concentration (Cmax) in Part 1 of DTG in Plasma

Description

Time Frame

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

Title

AUC(0-inf) in Part 1 of ABC

Description

Time Frame

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

Title

AUC(0-t) in Part 1 of ABC

Description

Time Frame

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

Title

Cmax in Part 1 of ABC in Plasma

Description

Time Frame

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

Title

AUC(0-inf) in Part 1 of 3TC

Description

Time Frame

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

Title

AUC (0-t) in Part 1 of 3TC

Description

Time Frame

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

Title

Cmax in Part 1 of 3TC

Description

Time Frame

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

Title

AUC(0-inf) in Part 2 of DTG in Plasma

Description

Time Frame

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

Title

AUC(0-t) in Part 2 of DTG

Description

Time Frame

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

Title

Cmax in Part 2 of DTG in Plasma

Description

Time Frame

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

Title

AUC(0-inf) in Part 2 of 3TC

Description

Time Frame

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

Title

AUC(0-t) in Part 2 of 3TC

Description

Time Frame

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

Title

Cmax in Part 2 of 3TC

Description

Time Frame

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 Measure Information:

Title

AUC From Time of Dose to 24 Hours (AUC[0-24]) of DTG in Part 1

Description

Time Frame

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

Title

Time to Maximum Concentration (Tmax) of DTG in Plasma in Part 1

Description

Time Frame

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

Title

Time of Last Quantifiable Concentration (Tlast) of DTG in Part 1

Description

Time Frame

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

Title

Apparent Oral Clearance (CL/F) of DTG in Plasma in Part 1

Description

Time Frame

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

Title

Apparent Volume of Distribution (Vz/F) of DTG in Part 1

Description

Time Frame

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

Title

Observed Concentration at 24 Hours Postdose (C24) of DTG in Plasma in Part 1

Description

Time Frame

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

Title

Last Observed Quantifiable Concentration (Ct) of DTG in Plasma in Part 1

Description

Time Frame

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

Title

Terminal Elimination Phase Half-life (t½) of DTG in Plasma in Part 1

Description

Time Frame

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

Title

Lag Time for Absorption (Tlag) of DTG in Part 1

Description

Time Frame

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

Title

AUC(0-24) of ABC in Plasma in Part 1

Description

Time Frame

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

Title

Tmax of ABC in Plasma in Part 1

Description

Time Frame

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

Title

Tlast of ABC in Part 1

Description

Time Frame

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

Title

CL/F of ABC in Plasma in Part 1

Description

Time Frame

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

Title

Vz/F of ABC in Part 1

Description

Time Frame

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

Title

C24 of ABC in Plasma in Part 1

Description

Time Frame

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

Title

Ct of ABC in Plasma in Part 1

Description

Time Frame

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

Title

T½ of ABC in Plasma in Part 1

Description

Time Frame

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

Title

AUC(0-24) of 3TC in Plasma in Part 1

Description

Time Frame

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

Title

Tmax of 3TC in Part 1

Description

Time Frame

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

Title

Tlast of 3TC in Plasma in Part 1

Description

Time Frame

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

Title

CL/F of 3TC in Plasma in Part 1

Description

Time Frame

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

Title

Vz/F of 3TC in Plasma in Part 1

Description

Time Frame

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

Title

C24 of 3TC in Plasma in Part 1

Description

Time Frame

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

Title

Ct of 3TC in Plasma in Part 1

Description

Time Frame

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

Title

T½ of 3TC in Plasma in Part 1

Description

Time Frame

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

Title

AUC (0-24) of DTG in Plasma in Part 2

Description

Time Frame

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

Title

Tmax of DTG in Plasma in Part 2

Description

Time Frame

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

Title

Tlast of DTG in Plasma in Part 2

Description

Time Frame

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

Title

CL/F of DTG in Plasma in Part 2

Description

Time Frame

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

Title

Vz/F of DTG in Plasma in Part 2

Description

Time Frame

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

Title

C24 of DTG in Plasma in Part 2

Description

Time Frame

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

Title

Ct of DTG in Plasma in Part 2

Description

Time Frame

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

Title

T½ of DTG in Plasma in Part 2

Description

Time Frame

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

Title

Tlag of DTG in Plasma in Part 2

Description

Time Frame

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

Title

AUC (0-24) of 3TC in Plasma in Part 2

Description

Time Frame

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

Title

Tmax of 3TC in Plasma in Part 2

Description

Time Frame

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

Title

Tlast of 3TC in Plasma in Part 2

Description

Time Frame

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

Title

CL/F of 3TC in Plasma in Part 2

Description

Time Frame

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

Title

Vz/F of 3TC in Plasma in Part 2

Description

Time Frame

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

Title

C24 of 3TC in Plasma in Part 2

Description

Time Frame

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

Title

Ct of 3TC in Plasma in Part 2

Description

Time Frame

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

Title

T½ of 3TC in Plasma in Part 2

Description

Time Frame

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

Title

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) in Part 1

Description

Time Frame

Up to Day 33

Title

Number of Participants With AEs and Serious Adverse Events SAEs in Part 2

Description

Time Frame

Up to Day 33

Title

Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea

Description

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotranferase (AST) and Creatinine Phosphokinase (CPK)

Description

Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CPK.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein

Description

Blood samples were collected for the analysis of clinical chemistry parameters including albumin and protein.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin

Description

Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea

Description

Blood samples were collected for the analysis of clinical chemistry parameters including glucose, calcium, potassium, sodium and urea.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK

Description

Blood samples were collected for the analysis of clinical chemistry parameters including ALT, ALP, AST and CPK.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein

Description

Blood samples were collected for the analysis of clinical chemistry parameters including albumin and protein.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin

Description

Blood samples were collected for the analysis of clinical chemistry parameters including bilirubin, creatinine and direct bilirubin.

Time Frame

Day 2 of each treatment period

Title

Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Glucose, Calcium, Potassium, Sodium and Urea

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: ALT, ALP, AST and CPK

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Albumin and Protein

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline in Clinical Chemistry Parameters Measured in Part 1: Bilirubin, Creatinine and Direct Bilirubin

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Glucose, Calcium, Potassium, Sodium and Urea

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: ALT, ALP, AST and CPK

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Albumin and Protein

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline in Clinical Chemistry Parameters Measured in Part 2: Bilirubin, Creatinine and Direct Bilirubin

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1

Description

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1

Description

Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 1 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Erythrocytes in Part 1

Description

Blood samples were collected for the analysis erythrocytes in Part 1 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Hemocrit in Part 1

Description

Blood samples were collected for the analysis hemocrit in Part 1 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Hemoglobin in Part 1

Description

Blood samples were collected for the analysis hemoglobin in Part 1 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2

Description

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2

Description

Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 2 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Erythrocyte Mean Corpuscular Volume in Part 2

Description

Blood samples were collected for the analysis erythrocyte mean corpuscular hemoglobin in Part 2 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Erythrocytes in Part 2

Description

Blood samples were collected for the analysis erythrocytes in Part 2 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Hemocrit in Part 2

Description

Blood samples were collected for the analysis hemocrit in Part 2 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Absolute Values for Hemoglobin in Part 2

Description

Blood samples were collected for the analysis hemoglobin in Part 2 at indicated time points.

Time Frame

Day 2 of each treatment period

Title

Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 1

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 1

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 1

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Erythrocytes in Part 1

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Hemocrit in Part 1

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Hemoglobin in Part 1

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Hematology Parameters Including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes and Platelets in Part 2

Description

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.

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Erythrocyte Mean Corpuscular Hemoglobin in Part 2

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Erythrocyte Mean Corpuscular Volume in Part 2

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Erythrocytes in Part 2

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Hemocrit in Part 2

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Change From Baseline Values for Hemoglobin in Part 2

Description

Time Frame

Baseline (Day -1) and Day 2

Title

Number of Participants With Abnormal Urinalysis Parameter in Part 1

Description

Time Frame

Up to Day 33

Title

Number of Participants With Urine Potential of Hydrogen (pH)-Part 1

Description

Time Frame

Up to Day 33

Title

Number of Participants With Abnormal Urinalysis Parameter in Part 2

Description

Time Frame

Up to Day 33

Title

Number of Participants With Urine Potential of Hydrogen (pH)-Part 2

Description

Time Frame

Up to Day 33

Title

Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Part 1

Description

Time Frame

Baseline (Day -1)

Title

Number of Participants With Abnormal ECG Findings in Part 2

Description

Time Frame

Baseline (Day -1)

Title

Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Part 1

Description

Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

Time Frame

Day 1 at 4 hours post intervention and Day 2 of each treatment period

Title

Absolute Values for Pulse Rate in Part 1

Description

Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

Time Frame

Day 1 at 4 hours post intervention and Day 2 of each treatment period

Title

Absolute Values for Temperature in Part 1

Description

Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

Time Frame

Day 1 at 4 hours post intervention dose and Day 2 of each treatment period

Title

Absolute Values for SBP and DBP of Part 2

Description

Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

Time Frame

Day 1 at 4 hours post intervention dose and Day 2 of each treatment period

Title

Absolute Values for Pulse Rate in Part 2

Description

Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

Time Frame

Day 1 at 4 hours post intervention dose and Day 2 of each treatment period

Title

Absolute Values for Temperature in Part 2

Description

Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest.

Time Frame

Day 1 at 4 hours post intervention dose and Day 2 of each treatment period

Title

Change From Baseline in SBP and DBP of Part 1

Description

Time Frame

Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2

Title

Change From Baseline in Pulse Rate of Part 1

Description

Time Frame

Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2

Title

Change From Baseline in Temperature of Part 1

Description

Time Frame

Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2

Title

Change From Baseline in SBP and DBP of Part 2

Description

Time Frame

Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2

Title

Change From Baseline in Pulse Rate in Part 2

Description

Time Frame

Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2

Title

Change From Baseline in Temperature in Part 2

Description

Time Frame

Baseline (Day 1, pre-dose), Day 1- 4 hours and Day 2

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

ViiV Healthcare

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Austin

State/Province

Texas

ZIP/Postal Code

78744

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

IPD Sharing Time Frame

IPD will be made available, within 6 months of publishing the results of the primary endpoints of the study.

IPD Sharing Access Criteria

Access is provided, after a research proposal is submitted and has submitted approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided, for an initial period of 12 months but an extension can be granted, when justified for up to another 12 months.

IPD Sharing URL

http://clinicalstudydatarequest.com

Citations:

PubMed Identifier

34817414

Citation

Singh RP, Adkison KK, Baker M, Parasrampuria R, Wolstenholme A, Davies M, Sewell N, Brothers C, Buchanan AM. Development of Dolutegravir Single-entity and Fixed-dose Combination Formulations for Children. Pediatr Infect Dis J. 2022 Mar 1;41(3):230-237. doi: 10.1097/INF.0000000000003366.

Results Reference

derived

Learn more about this trial

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

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