Clinical trial NCT01689623: A Pharmacokinetic Interaction Study Between TMC435, Atorvastatin and Simvastatin in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Healthy participants
TMC435
HMG-CoA reductase inhibitors
Atorvastatin
Simvastatin
Pharmacokinetic interaction
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2012-09-21
Enrollment: 36
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Effect of steady-state (constant concentration of medication in the blood) concentrations of TMC435 on the single dose pharmacokinetics (what the body does to the drug) of simvastatin and the active metabolite simvastatin acid
timeFrame: Up to Day 16
measure: Effect of steady-state concentrations of TMC435 on the single dose pharmacokinetics of atorvastatin and the active metabolites ortho- and parahydroxylated atorvastatin
timeFrame: Up to Day 16
measure: 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
timeFrame: Up to Day 16
Secondary outcomes:
measure: To evaluate the steady-state pharmacokinetics of TMC435 in the presence of atorvastatin or simvastatin
timeFrame: Up to Day 16
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: Up to Day 24
Other outcomes:
Locations:
city: Lincoln
country: United States
state: Nebraska
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: