Bioequivalence and Food Effect Assessment of 2 Fixed‐Dose Combination Formulations of Dolutegravir and Lamivudine

Abstract

This single-dose study evaluated the bioequivalence, food effect, and safety of 2 experimental, 2-drug, fixed-dose formulations of 50 mg dolutegravir and 300 mg lamivudine (formulation AH and formulation AK) as compared with coadministration of single-entity tablets of 50 mg dolutegravir and 300 mg lamivudine (reference). In fasted subjects, formulation AH lamivudine exposure was similar to the reference; however, dolutegravir exposure was consistently higher in formulation AH, with area under the concentration-time curve (AUC) and maximum concentration (C max ) approximately 27% to 28% greater than reference. Formulation AK met bioequivalence standards to the reference for dolutegravir (AUC 0-Ý and C max ) and lamivudine (AUC 0-Ý and AUC 0-t ) exposure; however, dolutegravir AUC 0-t and lamivudine C max were approximately 16% and 32% higher than the reference, respectively. A high-fat meal increased dolutegravir AUC and C max by up to 33% and 21%, respectively, and decreased lamivudine C max by approximately 30%. Both test and reference formulations were well tolerated. The results support further development of formulation AK as a novel, 2-drug, fixed-dose combination tablet treatment for patients with HIV.