This was a single-center, two-part, open-label study. The study was conducted in accordance with the principles of Good Clinical Practice and was approved by the appropriate

institutional review boards and regulatory agencies. All subjects provided written informed consent prior to participation in study-related procedures. Healthy adult male and female subjects aged 18-55 years with an inclusive body mass index (BMI) of 18-32 kg/m2 were enrolled. All subjects were required to be free of any clinically significant disease and have clinical laboratory tests (including complete

blood counts, blood chemistries, Selleckchem Sotrastaurin Autophagy activator urinalysis, electrocardiogram, and vital signs) within normal limits or clinically acceptable to the investigator. Premenopausal women and men were required to use a medically accepted method of contraception. All subjects were required to provide written informed consent and to adhere to dose and visit schedules. No information on CYP3A4/5 polymorphisms in the study subjects was available prior to dosing. Subjects who were pregnant, breastfeeding, or who (in the opinion of the investigator) were unable to participate optimally in new the study

were excluded. Additional exclusion criteria were: a surgical or medical condition that might significantly alter the absorption, distribution, metabolism, or excretion of any drug; a recent history of any infectious disease; and infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). Subjects with a history of alcohol or drug abuse in the past 2 years, who smoked >10 cigarettes or had equivalent tobacco use per day, or who had elevated liver function tests also were excluded. This study consisted of two parts, each with a fixed-sequence design. Part 1 was designed to assess the effect of cyclosporine on boceprevir PK and the effect of boceprevir on cyclosporine PK (Fig. 1A). In part 2, the effect of boceprevir on tacrolimus PK and the effect of tacrolimus on boceprevir PK were assessed (Fig. 1B). In both parts of the study, boceprevir was administered orally as 4 × 200-mg capsules swallowed (not crushed or chewed) with a glass of water. A meal or light snack preceded boceprevir.