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

NCT04827134 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 216149
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections

Keywords

TRIUMEQ; DOVATO; Pharmacokinetics; Food effect; Dolutegravir; Abacavir; Lamivudine

Outcome Measures

Primary Outcomes (6)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary Outcomes (46)

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

  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

  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

  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

  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

  24 hours post dose in treatment periods 1 and 2

Study Arms (4)

Cohort 1: TRIUMEQ Fed followed by TRIUMEQ Fasted

EXPERIMENTAL

Participants received TRIUMEQ (dolutegravir \[DTG\] 5 milligram \[mg\]/abacavir \[ABC\] 60 mg/lamivudine \[3TC\] 30 mg), dispersible tablets administered as a dispersion immediately after a high calorie meal (under fed condition) (Treatment A) in treatment period 1 followed by TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg), dispersible tablets administered as a dispersion under fasted conditions (Treatment B) in treatment period 2. The treatment periods were separated by a washout period of about 7 days. All participants were followed-up for 7 to 14 days of last dose in treatment period 2.

Drug: TRIUMEQ

Cohort 1: TRIUMEQ Fasted followed by TRIUMEQ Fed

EXPERIMENTAL

Participants received TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg), dispersible tablets administered as a dispersion under fasted conditions (Treatment B) in treatment period 1 followed by TRIUMEQ (DTG 5 mg/ABC 60 mg/3TC 30 mg), dispersible tablets administered as a dispersion immediately after a high calorie meal (under fed condition) (Treatment A) in treatment period 2. The treatment periods were separated by a washout period of about 7 days. All participants were followed-up for 7 to 14 days of last dose in treatment period 2.

Drug: TRIUMEQ

Cohort 2: DOVATO Fed followed by DOVATO Fasted

EXPERIMENTAL

Participants received DOVATO (DTG 5 mg/3TC 30 mg), dispersible tablets administered as a dispersion immediately after a high calorie meal (under fed condition) (Treatment C) in treatment period 1 followed by DOVATO (DTG 5 mg/3TC 30 mg), dispersible tablets administered as a dispersion under fasted conditions (Treatment D) in treatment period 2. The treatment periods were separated by a washout period of about 7 days. All participants were followed-up for 7 to 14 days of last dose in treatment period 2.

Drug: DOVATO

Cohort 2: DOVATO Fasted followed by DOVATO Fed

EXPERIMENTAL

Participants received DOVATO (DTG 5 mg/3TC 30 mg), dispersible tablets administered as a dispersion under fasted conditions (Treatment D) in treatment period 1 followed by DOVATO (DTG 5 mg/3TC 30 mg), dispersible tablets administered as a dispersion immediately after a high calorie meal (under fed condition) (Treatment C) in treatment period 2. The treatment periods were separated by a washout period of about 7 days. All participants were followed-up for 7 to 14 days of last dose in treatment period 2.

Drug: DOVATO

Interventions

TRIUMEQ DRUG

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

Cohort 1: TRIUMEQ Fasted followed by TRIUMEQ Fed; Cohort 1: TRIUMEQ Fed followed by TRIUMEQ Fasted

DOVATO DRUG

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

Cohort 2: DOVATO Fasted followed by DOVATO Fed; Cohort 2: DOVATO Fed followed by DOVATO Fasted

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

abacavir, dolutegravir, and lamivudine drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label study
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, single-dose, 2-cohort, 2-period crossover study.

Study Record Dates

• First Submitted: March 23, 2021
• First Posted: April 1, 2021
• Study Start: May 7, 2021
• Primary Completion: July 23, 2021
• Study Completion: July 23, 2021
• Last Updated: June 5, 2023
• Results First Posted: June 5, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received 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.

Locations

US (1)