Effect of Food Intake or Coadministration With an Acid‐Reducing Agent on Lenacapavir Pharmacokinetics Following Oral Administration

Abstract Lenacapavir is a potent, long‐acting HIV‐1 capsid inhibitor used in combination with other antiretrovirals to treat HIV‐1 infection. The pharmacokinetics of orally administered drugs may be affected by food intake or coadministration of acid‐reducing agents (ARA). Two Phase 1 studies were conducted on healthy participants to evaluate the effect of food and the impact of the histamine H 2 ‐receptor antagonist famotidine in parallel cohorts. In Study 1, oral lenacapavir (300 mg) was administered under fasting conditions, after a standardized high‐fat meal, and after a low‐fat meal (n = 8/cohort). In Study 2, lenacapavir 300 mg was administered alone (n = 27) and 2 hours after famotidine (40 mg; n = 25), each under fasting conditions. For the high‐fat meal versus fasted comparison, the percentage geometric least‐squares mean (%GLSM) ratios for the lenacapavir area under the curve to infinity (AUC inf ) and maximum concentration (C max ) were 115.2 and 145.2, respectively. For the low‐fat meal, the %GLSM ratios for lenacapavir AUC inf and C max were 98.6 and 115.8, respectively, versus the fasted state. In the famotidine study, the %GLSM ratio for lenacapavir AUC from time zero to the last quantifiable concentration was 137.4, and for C max was 100.6. Based on available clinical safety data, the exposure increases observed in these studies were not expected to be clinically relevant. Overall, these data support the dosing of oral lenacapavir without regard to food intake or coadministration with ARAs.