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

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‐∞) and C(max)) and lamivudine (AUC(0‐∞) 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.