This study is a single-center, randomized, open-label, two cohorts, 3-way cross-over design in 36 subjects to assess the oral bioavailability of four new cabotegravir (CAB) sodium salt tablet formulations relative to the current CAB sodium salt formulation being used in the phase IIb studies under fasting conditions. All treatments will be administered as single 30 mg doses of CAB. Safety evaluations and serial PK samples will be collected during each treatment period. A follow-up visit will occur 10 - 14 days after the last dose of study drug. Treatment period doses will be separated by a 14 day washout. Participation in this study will be approximately 12 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Cabotegravir 30 mg current formulation (Treatment A) is a film coated tablet with a weight of 824 mg
Cabotegravir 30 mg micronized new formulation 500 M (Treatment B) is a film coated tablet with a weight of 515 mg
Cabotegravir 30 mg unmicronized new formulation 500 U (Treatment C) is a film coated tablet with a weight of 515 mg
Cabotegravir 30 mg micronized new formulation 650 M (Treatment D) is a film coated tablet with a weight of 670 mg
Cabotegravir 30 mg unmicronized new formulation 650 U (Treatment E) is a film coated tablet with a weight of 670 mg
GSK Investigational Site
Overland Park, Kansas, United States
Composite of pharmacokinetic (PK) parameters for cabotegravir evaluated by measurement of plasma AUC (0-infinity), AUC (0-t) and Cmax and C24
To evaluate the relative bioavailability of cabotegravir after single 30 mg dose in the fasted state, the following PK parameters will be assessed: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC(0-infinity)), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration within a subject across all treatments (AUC (0-t)), maximum observed concentration (Cmax) and concentration at 24 hours post-dose (C24)
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120 and 168 hours post dose.
Composite of PK parameters for cabotegravir evaluated by measurement of plasma t1/2, tlag, tmax, %AUCex, AUC (0-72), and CL/F
Other plasma PK parameters of cabotegravir from new formulations that will be compared to the current formulation are the following:terminal phase half-life (t ½) , lag time before observation of drug concentrations in sampled matrix (tlag), time of occurrence of Cmax (tmax), percentage of AUC(0-infinity) obtained by extrapolation (%AUCex), area under the concentration-time curve from time zero to 72 hours post dose (AUC (0-72), time of last measurable concentration (tlast) and apparent clearance following oral dosing (CL/F) after single 30 mg dose in the fasted state
Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 120 and 168 hours post dose.
Number of participants with adverse events as a measure of safety and tolerability of Cabotegravir
Safety and tolerability of cabotegravir will be assessed by clinical safety data from number of participants with adverse event. Adverse events will be collected from the start of study treatment and until the final follow-up visit. Intensity of AEs will be categorized as mild, moderate or severe.
Time frame: Up to 8 weeks
Safety and tolerability of single oral dose of Cabotegravir assessed by concurrent medication used any time during the study period along with the study medication.
Time frame: Up to 8 weeks
Safety and tolerability of single oral dose of Cabotegravir assessed by clinical laboratory screens
Safety laboratory tests will include hematology, clinical chemistry and additional parameters
Time frame: Up to 8 weeks
Safety and tolerability of single oral dose of Cabotegravir assessed by12-lead electrocardiogram
Time frame: Up to 8 weeks
Safety and tolerability of single oral dose of Cabotegravir assessed by vital signs
Vital signs will include systolic and diastolic blood pressure and pulse rate.
Time frame: Up to 8 weeks
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