Relative Bioavailability Study of a Pediatric Granule Formulation of Dolutegravir
Dolutegravir (DTG, GSK1349572) is an integrase inhibitor currently in Phase 3 clinical trials for the treatment of human immunodeficiency virus (HIV) infection. A granule formulation has been developed as an alternative to the current tablet formulation for administration in pediatric populations.
This is a single-center, randomized, open-label, 5-way crossover study in healthy adult subjects. The study will evaluate the relative bioavailability of a 50 mg granule formulation of dolutegravir when administered 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula compared to the current 50 mg tablet formulation administered with tap water. Safety evaluations and serial PK samples will be collected during each treatment period. A taste assessment of the granule will also be performed. A follow-up visit will occur 5-7 days after the last dose of study drug.
Pharmacokinetic assessments during the study will include 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), terminal phase half-life (t½), lag time before observation of drug concentrations in sampled matrix (tlag), time of occurrence of Cmax (tmax), concentration at 24 hours post-dose (C24), and apparent clearance following oral dosing (CL/F).
Infections, Human Immunodeficiency Virus and Herpesviridae
Drug: Dolutegravir 50 mg tablet
Drug: Dolutegravir 50 mg oral granules
|Study Design:||Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
|Official Title:||Relative Bioavailability Study of a Tablet Formulation vs. Pediatric Granule Formulation of Dolutegravir 50 mg and Effect of Different Types of Water Plus Infant Formula on the Pediatric Granule Formulation in Healthy Male and Female Volunteers|
- Plasma DTG AUC(0-infinity), AUC(0-t), and Cmax [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
- Plasma DTG t½, tlag, tmax, C24, and CL/F [ Time Frame: 48 hours post dose ] [ Designated as safety issue: No ]
- Safety and tolerability parameters as assessed by change from baseline in 12-lead ECG and vital signs (BP and HR), number of subjects with adverse events and toxicity grading of clinical laboratory tests [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||June 2011|
|Study Completion Date:||August 2011|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
Experimental: Single arm
Subjects will have a screening visit within 30 days prior to the first dose of study drug, five treatment periods containing a single dose of study drug, followed by 48 hours of serial PK collection. In the 5 treatment periods subjects will receive DTG granule formulation 1) directly to mouth; 2) with purified water; 3) with Contrex brand water; and 4) with milk-based infant formula. They will also receive the current 50 mg tablet formulation administered with tap water. These treatments will be administered in a random order. Subjects will check out of the unit on Day 3 after the 48 hour PK sample in each period. Study periods will be separated by at least 5 days. Subjects will have a follow-up visit 5-7 days after last dose of DTG given.
Drug: Dolutegravir 50 mg tablet
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.Drug: Dolutegravir 50 mg oral granules
Dolutegravir is an experimental drug in the integrase inhibitor class for the treatment of HIV.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01382238
|United States, Texas|
|GSK Investigational Site|
|Austin, Texas, United States, 78744|
|Study Director:||GSK Clinical Trials||ViiV Healthcare|