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NCT03836729

Study to Evaluate the Effect of GSK3640254 on the Pharmacokinetics of Tenofovir Alafenamide/Emtricitabine

Completed Phase 1 Results posted Last updated 21 April 2020
What this trial tests

Phase 1 trial testing Tenofovir alafenamide/emtricitabine in HIV Infections in 16 participants. Completed in 30 April 2019.

Timeline
11 February 2019
Primary endpoint
30 March 2019
30 April 2019

Quick facts

Lead sponsorViiV Healthcare
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Designsequential
Maskingnone
Primary purposetreatment
Enrollment16
Start date11 February 2019
Primary completion30 March 2019
Estimated completion30 April 2019
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

ViiV Healthcare — full company profile →

Who can join

Adults 18 to 55, any sex, with HIV Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing Interval at Steady State (AUC [0-tau]) of TAF Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14

Blood samples were collected at indicated time-points for analysis of AUC (0-tau). Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.

GroupValue95% CI
TAF/FTC250.4± 58.2
Period 2: AUC (0-tau) of TAF Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7

Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC+GSK3640254215.4± 36.3
Period 1: Maximum Observed Concentration (Cmax) of TAF Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14

Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC203.4± 56.1
Period 2: Cmax of TAF Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7

Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC+GSK3640254175.1± 44.4
Period 1: AUC (0-tau) of FTC Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14

Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC9787.5± 15.5
Period 2: AUC (0-tau) of FTC Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7

Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC+GSK36402549421.0± 14.4
Period 1:Cmax of FTC Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14

Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC1811± 15.9
Period 2:Cmax of FTC Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7

Blood samples were collected at indicated time-points for analysis of Cmax. PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC+GSK36402541701± 20.9
Period 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of FTC Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14

Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC71.81± 25.5
Period 2: Ctau of FTC Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7

Blood samples were collected at indicated time-points for analysis of Ctau. PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC+GSK364025482.92± 29.1
Period 1: AUC (0-tau) of Tenofovir (TFV) Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 1 Day 14

Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC221.9± 18.3
Period 2: AUC (0-tau) of TFV Primary · Pre-dose, 15, 30, 45 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 4, 5, 6, 8, 12 and 24 hours in Period 2 Day 7

Blood samples were collected at indicated time-points for analysis of AUC (0-tau). PK parameters were calculated by standard non-compartmental analysis.

GroupValue95% CI
TAF/FTC+GSK3640254229.1± 21.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Non-serious AEs and SAEs were collected from the start of the study treatment up to Day 24. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

TAF/FTC
Serious: 0/16 (0%)
Deaths: 0/16
TAF/FTC+GSK3640254
Serious: 0/16 (0%)
Deaths: 0/16
Other adverse events (16 terms — click to expand)

ReactionSystemTAF/FTCTAF/FTC+GSK3640254
Upper respiratory tract infectionInfections and infestations
Rash pustularInfections and infestations
NauseaGastrointestinal disorders
ConjunctivitisInfections and infestations
Abdominal discomfortGastrointestinal disorders
VomitingGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
SomnolenceNervous system disorders
Ingrown hairSkin and subcutaneous tissue disorders
UrticariaSkin and subcutaneous tissue disorders
LymphadenopathyBlood and lymphatic system disorders
Seasonal allergyImmune system disorders
Abnormal dreamsPsychiatric disorders
Rhinitis allergicRespiratory, thoracic and mediastinal disorders

Data from ClinicalTrials.gov NCT03836729 adverse events section.

Sponsor's own description

Human immunodeficiency virus (HIV) infection frequently involves combination drug therapy for its treatment; hence, it is important to understand their interactions and resulting changes in exposure which are associated with medications. This is a Phase-1, open-label, fixed-sequence 2-period, one-way drug interaction study to assess the pharmacokinetic (PK), safety, and tolerability of GSK3640254 and Tenofovir alafenamide/emtricitabine (TAF/FTC) when administered alone and in combination in healthy subjects. The study will consist of a screening period of 28 days before the first dose of study intervention followed by 2 sequential treatment periods. Subjects will be administered TAF/FTC 25/200 milligram (mg) once daily (QD) on Days 1 to 14 of Period 1 followed by co-administration of TAF/FTC 25/200 mg QD with GSK3640254 200 mg QD on Days 1 to 7 of Period 2.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. A Phase I Evaluation of the Pharmacokinetics and Tolerability of the HIV-1 Maturation Inhibitor GSK3640254 and Tenofovir Alafenamide/Emtricitabine in Healthy Participants.
    Pene Dumitrescu T, Joshi SR, Xu J, Zhan J, et al · · 2021 · cited 13× · PMID 33753329 · DOI 10.1128/aac.02173-20

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