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

ViiV Healthcare33 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HIV Infections

Interventions

TRIUMEQDRUG

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

DOVATODRUG

DOVATO will be available as FDC dispersible tablets to be administered orally as a dispersion.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent. * Participants who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG). * Body weight \>=50.0 kilograms (kg) (110 pounds \[lbs.\]) for males and \>=45 kg (99 lbs.) for females and body mass index within the range 18.5 to 31.0 kilogram per meter square (kg/m\^2, inclusive). * A male participant is eligible to participate if they agree to use contraceptive methods. * A female participant is eligible to participate if she is not pregnant (, not lactating or breastfeeding, and at least 1 of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and using a non-hormonal contraceptive method that is highly effective * Capable of giving signed informed consent * Documentation that the participant is negative for the human leukocyte antigen (HLA) B\*5701 allele. Exclusion Criteria: * Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome. * A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study intervention. * QT interval corrected for heart rate according to Fridericia's formula (QTcF) \>450 milliseconds (msec). * A participant with known or suspected active coronavirus disease (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment. * Presence of hepatitis B surface antigen at screening or within 3 months prior to starting study intervention. * Positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention AND positive on reflex to hepatitis C ribonucleic acid (RNA). * Positive human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at screening. * Alanine aminotransferase (ALT) \>1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility. * Bilirubin \>1.5 × ULN (isolated bilirubin \>1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility. * Any acute laboratory abnormality at screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound. * Any Grade 2 to 4 laboratory abnormality at screening, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT (described above), will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility. * A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at screening or before the first dose of study intervention. * Unable to refrain from the use of prescription or non-prescription drugs including vitamins, herbal and dietary supplements (including St. John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention and for the duration of the study until completion of the follow-up visit, unless, in the opinion of the investigator and ViiV Healthcare (VH)/GlaxoSmithKline medical monitor, the medication will not interfere with the study procedures or compromise participant safety. * Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study. * Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to Day 1 of Period 1 in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the study intervention (whichever is longer). * Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 60 days. * Estimated serum creatinine clearance (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\]) \<90 milliliter per minute (mL/min). * History of regular alcohol consumption within 6 months of the study, defined as an average weekly intake of \>14 units for males or \>7 drinks for females. * Unable to refrain from tobacco or nicotine-containing products within 1 month prior to screening. * History of sensitivity, prior intolerance or hypersensitivity to any of the study interventions, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.

Locations (1)

GSK Investigational Site

Austin, Texas, United States

Outcomes

Primary Outcomes

Cohort 1: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinity (AUC [0-inf]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 1: AUC From Time Zero to Time of Last Observed Quantifiable Concentration (AUC [0-t]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 1: Maximum Observed Concentration (Cmax) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 2: AUC (0-inf) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 2: AUC (0-t) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions

Data from ClinicalTrials.gov

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Secondary Outcomes

Cohort 1: Lag Time for Absorption (Tlag) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 1: Terminal Elimination Phase Half-life (t1/2) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 1: AUC From Time Zero to 24 Hours (AUC[0-24]) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12 and 24 Hours post dose in each treatment periods 1 and 2

Cohort 1: Last Quantifiable Concentration (Ct) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 1: Concentration at 24 Hours Post-dose (C24) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: 24 hours post dose in treatment periods 1 and 2

Cohort 1: Time of Maximum Observed Concentration (Tmax) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG, ABC and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 2: Tlag of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 2: t1/2 of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 2: AUC(0-24) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12 and 24 Hours post dose in each treatment periods 1 and 2

Cohort 2: Ct of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Cohort 2: C24 of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: 24 hours post dose in treatment periods 1 and 2

Cohort 2: Tmax of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions

Blood samples were collected at indicated time points for pharmacokinetic analysis of DTG and 3TC. The PK parameters were calculated by standard non-compartmental analysis.

Time frame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment.

Time frame: Up to 23 days

Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and Neutrophil

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value for each period, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.