Bioequivalence Study of a Fixed-dose Combination (FDC) of Dolutegravir (DTG) and Rilpivirine (RPV)
Condition: Infection, Human Immunodeficiency Virus; HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to evaluate the bioequivalence between Fixed-dose Combination
      (FDC) tablet formulation of Dolutegravir (DTG) 50 milligrams (mg) and Rilpivirine (RPV) 25 mg
      versus co-administration of the separate tablet formulations of DTG 50 mg plus RPV 25 mg, in
      the fed state. This pivotal bioequivalence study, is to serve as a pharmacokinetic (PK)
      bridge to the ongoing Phase 3 trials with the separate agents. This study will be conducted
      under fed conditions to appropriately mimic the conditions in the Phase 3 trials. This is a
      single-center, randomized, open-label, 2-period, single-dose, crossover study. A minimum of
      86 healthy adult subjects will be randomized such that a minimum of approximately 82
      evaluable subjects complete the study. The total duration of participation of a subject in
      this study will be approximately 8 weeks which includes a screening visit within 30 days
      prior to the first dose of study drug, two treatment periods each with a single dose of study
      drug and a follow-up visit within 12-17 days after the last dose of study drug. There will be
      a washout of at least 21 days between each dose of study drug.

      A blinded (for treatment) review of DTG and RPV plasma concentration data for approximately
      the first 40 subjects will be conducted. If the within-subject coefficients of variation
      (CVw%) for either DTG or RPV maximal drug concentration (Cmax) values are >=31%; a sample
      size re-estimation will be employed and additional subjects (beyond the 86 planned) will be
      randomized for treatment in the study. Following the re-estimation, it is possible that up to
      approximately 154 healthy adult subjects (68 new subjects in addition to the planned 86
      subjects above) will be randomized such that a maximum of approximately 146 evaluable
      subjects could complete the study.
    


Intervention name(s): DTG; RPV; DTG/RPV FDC
Intervention type(s): Drug; Drug; Drug
Intervention description(s): DTG is provided as a white, film-coated, round tablet containing DTG 50 mg, debossed with SV 572 on one side and 50 on the other side. Subjects will receive a single oral dose of DTG 50 mg tablet with 240 mL of water.; RPV is provided as a white to off-white, film-coated, round, biconvex tablet containing RPV 25 mg, debossed with TMC on one side and 25 on the other side. Subjects will receive a single oral dose of RPV 25 mg tablet with 240 mL of water.; DTG/RPV FDC is provided as a pink, film coated, oval biconvex tablet containing FDC of DTG 50 mg and RPV 25 mg, debossed with SV J3T on one face. Subjects will receive a single oral dose of DTG/RPV 50 mg/25 mg FDC tablet with 240 mL of water.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Fixed-dose Combination (FDC); Bioequivalence; Dolutegravir; Rilpivirine