A Pharmacokinetic Interaction Study Between TMC435, Atorvastatin and Simvastatin in Healthy Participants

A Phase I, 2-Panel, Open-Label Study in Healthy Subjects to Investigate the Pharmacokinetic Interaction Between TMC435 and the HMG-CoA Reductase Inhibitors Atorvastatin and Simvastatin

The purpose of this study is to evaluate effects of steady-state concentrations (constant concentration of medication in the blood) of TMC435 on the single dose pharmacokinetics (what the body does to the medication) of atorvastatin, the active metabolites ortho- and parahydroxylated atorvastatin, simvastatin and the active metabolite simvastatin acid. Plasma hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitory activity after a single dose of atorvastatin or simvastatin, either alone or in combination with TMC435 will be also evaluated.

This is a Phase I, 2-panel, open-label (all people know the identity of the intervention) study in healthy participants to investigate the pharmacokinetic interaction between TMC435 and the HMG-CoA reductase inhibitors atorvastatin and simvastatin. The study consists of a screening period (21 days prior to the first intake of study medication), a 17-day treatment period and a 5-7 days follow-up period. Approximately thirty six healthy participants will be equally divided to 2 panels (n=18 per panel). Within each panel all participants will receive the same treatments in the same order. In Panel 1, each participant will be administered a single oral 40-mg atorvastatin dose on Day 1 and Day 13. The participants will receive TMC435 at a dose of 150 mg once daily from Day 4 until Day 15. In Panel 2, each participant will be administered a single oral 40-mg simvastatin dose on Day 1 and Day 13. TMC435 at a dose of 150 mg will be administered once daily from Day 4 until Day 15. Treatment duration (including Day -1) will be 17 days for both panels (Panel 1 and Panel 2). Safety and tolerability will be evaluated throughout the study.

Inclusion Criteria:

• Must be healthy on the basis of physical examination, medical history, vital signs, clinical laboratory tests, and 12-lead electrocardiogram performed at screening
• If a woman, before entry she must be postmenopausal for at least 2 years, as confirmed by follicle stimulating hormone test, or surgically sterile (have had a total hysterectomy or bilateral oophorectomy, tubal ligation/bilateral tubal clips), not heterosexually active for the duration of the study, or if of childbearing potential and heterosexually active, agree to use effective methods of birth control
• If a man and heterosexually active with a woman of childbearing potential, he must agree to use 2 effective methods of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
• Have a Body Mass Index (weight in kg divided by the square of height in meters) of 18.0 to 30.0 kg/m2

Exclusion Criteria:

• Has a history of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, neoplastic, or metabolic disturbances
• Has a positive Human immunodeficiency virus (HIV)-1 or HIV-2 test at screening
• Has a hepatitis A, B or C infection (confirmed by hepatitis A antibody immune globulin M, hepatitis B surface antigen, or Hepatitis C virus (HCV) antibody, respectively) at screening
• Pregnant or breastfeeding woman