Clinical pharmacology in drug development 2017 02 07() doi 10.1002/cpdd.332
Dolutegravir (DTG) is approved in the United States to treat HIV-1-infected patients weighing ≥30 kg. A dispersible DTG tablet formulation was recently developed for pediatric patients. This study compares the pharmacokinetics (PK) of the dispersible tablet with that of a previously evaluated granule formulation. In this randomized, open-label, crossover study, 15 healthy adults received single oral doses of DTG 20 mg every 7 days across 5 treatment arms: granules consumed immediately after mixture with purified water, dispersible DTG consumed immediately after reconstitution in low-mineral-content (LMC) or high-mineral-content (HMC) water, and dispersible DTG consumed 30 minutes after dispersal in LMC or HMC water. Primary endpoints were bioavailability of immediately consumed dispersible tablet in LMC water relative to granule formulation reconstituted in purified water and PK of the dispersible tablet. Secondary endpoints included tolerability and palatability. The DTG dispersible tablet showed equivalent exposures to the granule formulation with geometric least-squares mean treatment ratios of 1.06 and 1.12 for AUC0-∞ and Cmax , respectively. DTG PK parameters were unaffected by mineral content or the 30-minute delay. Adverse events were mild; only nausea (n = 1) was considered drug related. DTG exposure observed with the dispersible tablet supports evaluation of this formulation for further development.