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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
118
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.
GSK Investigational Site
Overland Park, Kansas, United States
Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUC[0-inf]) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
AUC from time 0 to the last measurable timepoint (AUC[0-t]) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Maximal drug concentration (Cmax) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Absorption lag time (tlag) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Time to observed maximal drug concentration (tmax) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Time of last quantifiable concentration (t) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Half-life (t1/2) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Apparent terminal elimination phase rate constant (lambda z) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Percentage of AUC(0-inf) resulting from extrapolation (%AUCex) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
AUC from time 0 to 24 hours (AUC[0-24]) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Apparent oral clearance (CL/F) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Apparent oral volume of distribution (Vz/F) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Last quantifiable concentration (Ct) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Concentration at 24 hours post-dose (C24) of DTG and RPV in plasma
Time frame: Blood samples will be collected at pre-dose and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 12, 16, 24, 48, 72, 120, 168, 216, and 264 hours post-dose during the 2 treatment periods.
Change from baseline in 12-lead electrocardiogram (ECG)
Time frame: Baseline and up to 8 weeks
Change from baseline in blood pressure (BP)
Time frame: Baseline and up to 8 weeks
Change from baseline in heart rate (HR)
Time frame: Baseline and up to 8 weeks
Number of subjects with any adverse events (AEs) and any serious adverse events (SAEs)
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function.
Time frame: Up to 4 weeks
Number of subjects with Grade 3/4 hematology parameters
Time frame: Up to 8 weeks
Number of subjects with Grade 3/4 clinical chemistry parameters
Time frame: Up to 8 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.