Clinical trial NCT04827134: A Food-effect Study of the Pediatric Dispersible Tablet Formulations of TRIUMEQ® and DOVATO® in Healthy Adult Participants
Official title: A Randomized, 2-Cohort, 2-Period, Single Dose, Crossover Clinical Study to Assess the Effect of Food on the Pediatric Dispersible Tablet Formulations of TRIUMEQ (Dolutegravir/Abacavir/Lamivudine) and DOVATO (Dolutegravir/Lamivudine) in Healthy Adult Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: TRIUMEQ
DOVATO
Pharmacokinetics
Food effect
Dolutegravir
Abacavir
Lamivudine
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a randomized, single-dose, 2-cohort, 2-period crossover study.
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Cohort 1: Maximum Observed Concentration (Cmax) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 2: AUC (0-inf) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 2: AUC (0-t) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 2: Cmax of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: Pre-dose, 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 48 and 72 Hours post dose in each treatment periods 1 and 2
Secondary outcomes:
measure: Cohort 1: Lag Time for Absorption (Tlag) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 1: Terminal Elimination Phase Half-life (t1/2) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions
timeFrame: 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
measure: 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
timeFrame: 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
measure: Cohort 1: Last Quantifiable Concentration (Ct) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 1: Concentration at 24 Hours Post-dose (C24) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions
timeFrame: 24 hours post dose in treatment periods 1 and 2
measure: Cohort 1: Time of Maximum Observed Concentration (Tmax) of DTG, ABC and 3TC Following Administration of TRIUMEQ Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 2: Tlag of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 2: t1/2 of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 2: AUC(0-24) of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 2: Ct of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: 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
measure: Cohort 2: C24 of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: 24 hours post dose in treatment periods 1 and 2
measure: Cohort 2: Tmax of DTG and 3TC Following Administration of DOVATO Under Fed and Fasted Conditions
timeFrame: 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
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 23 days
measure: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and Neutrophil
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Hematology Parameters: Red Blood Cell (RBC) Count
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Hematology Parameters: Hemoglobin
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Hematology Parameters: Hematocrit
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count and Neutrophil
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Hematology Parameters: RBC Count
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Hematology Parameters: Hemoglobin
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Hematology Parameters: Hematocrit
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Hematology Parameters: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Amino Transferase (AST)
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Blood Urea Nitrogen (BUN)
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin and Total Bilirubin
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Clinical Chemistry Parameters: Creatine Kinase
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Clinical Chemistry Parameters: Albumin and Total Protein
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Clinical Chemistry Parameters: ALT, ALP and AST
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and BUN
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin and Total Bilirubin
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Clinical Chemistry Parameters: Creatine Kinase
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Clinical Chemistry Parameters: Albumin and Total Protein
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Urinalysis Parameter: Specific Gravity
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) by Dipstick
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Urinalysis Parameter: Specific Gravity
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Urinalysis Parameter: Potential of Hydrogen (pH) by Dipstick
timeFrame: Baseline (Day -1) and Day 4
measure: Number of Participants With Abnormal Values on Urinalysis by Dipstick
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and Corrected QT Interval According to Fridericia's Formula (QTcF)
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Vital Signs Measurements: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Vital Signs Measurements: SBP and DBP
timeFrame: Baseline (Day -1) and Day 4
measure: Change From Baseline in Vital Signs Measurements: Pulse Rate
timeFrame: Baseline (Day -1) and Day 4
measure: Absolute Values of Vital Signs Measurements: Pulse Rate
timeFrame: Baseline (Day -1) and Day 4
Other outcomes:
Locations:
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: