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

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: Simvastatin; Drug: TMC435; Drug: Atorvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01689623

TMC435HPC1006 (Other Identifier)

CR100873

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 36 patients

Sex: All

Ages: 19 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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36 participants in 2 patient groups

Panel I

Experimental group

Description:

Each participant will be administered a single oral 40-mg atorvastatin dose on Day 1 and Day 13. The participants will receive TMC435 once daily dose of 150 mg from Day 4 until Day 15.

Treatment:

Drug: Atorvastatin

Drug: TMC435

Panel II

Experimental group

Description:

Each participant will be administered a single oral 40-mg simvastatin dose on Day 1 and Day 13. The participants will receive TMC435 once daily dose of 150 mg from Day 4 until Day 15.

Treatment:

Drug: TMC435

Drug: Simvastatin