A Study to Assess the Absolute Bioavailability and Pharmacokinetics of Simeprevir (TMC435) Administered as Single Oral Doses of TMC435 and an Intravenous Microdose of [3H]-TMC435 in Healthy Male Patients

NCT01707342 | Completed Phase 1

• 3 other identifiers: CR100901TMC435-TiDP16-C1182012-002330-37
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the absolute bioavailability and pharmacokinetics (what the body does to the medication) of simeprevir (TMC435) after administration of single oral doses of 50 mg and 150 mg when administered together with a single intravenous (IV) dose of 100 microgram \[3H\]-TMC435 in healthy male participants.

Conditions

Healthy Male Participants

Keywords

Healthy male participants; Absolute bioavailability; Bioavailability; Pharmacokinetics; Simeprevir; TMC435; [3H]-TMC435; Hepatitis C virus; HCV

Outcome Measures

Primary Outcomes (11)

• Absolute bioavailability of simeprevir (TMC435)

  Pre-dose Day 1, post-dose Days 1-4

• Volume of distribution of [3H]-TMC435 and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Maximum observed plasma concentration of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Time to reach the maximum observed plasma concentration of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Area under the concentration versus time curve from time of administration up to the last time point with a measurable concentration post dosing of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Area under the concentration versus time curve extrapolated to infinity of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Area under the first moment of the concentration versus time curve from the time of dosing up to a definite time, to infinity, or to the time of the last measureable concentration of [3H]-TMC435 and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Mean residence time of [3H]-TMC435 and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Terminal elimination rate constant of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Terminal elimination half-life of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

• Total systemic clearance of drug following single-dose intravenous administration of [3H]-TMC435 and [3H]-total radioactivity

  Pre-dose Day 1, post-dose Days 1-4

Secondary Outcomes (5)

• Total radioactivity excreted into the feces from time 0 to the time of discharge

  Post-dose Hours 5, 24, 48, 72, and 96

• Total radioactivity excreted into the feces expressed as a percentage of the administered dose

  Post-dose Hours 5, 24, 48, 72, and 96

• Total radioactivity excreted into urine from time 0 to the time of discharge

  Post-dose Hours 5, 24, 48, 72, and 96

• Total radioactivity excreted into the urine expressed as a percentage of the administered dose

  Post-dose Hours 5, 24, 48, 72, and 96

• Number of participants with adverse events

  up to 30 days after dose of study medications

Study Arms (1)

Simeprevir (TMC435)

EXPERIMENTAL

Treatment A: single oral dose of simeprevir (TMC435) 50 mg; and Treatment B: single oral dose of simeprevir (TMC435) 150 mg. A single 10 minute intravenous infusion of \[3H\]-TMC435 (100 microcurie) 100 microgram will be followed 5 hours later after administration of Treatment A and Treatment B in Period 1 and Period 2, respectively.

Drug: Simeprevir (TMC435)

Interventions

Simeprevir (TMC435) DRUG

Treatment A: Simeprevir (TMC435) 50 mg; and Treatment B: Simeprevir (TMC435) 150 mg; will be followed 5 hours later by a single 10 minute intravenous infusion of \[3H\]-TMC435 (100 microcurie) 100 microgram in Period 1 and Period 2, respectively.

Simeprevir (TMC435)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Must be healthy on the basis of physical examination, medical history, vital signs, 12-lead electrocardiogram, and clinical laboratory tests performed at screening
• Must be non-smoking for at least 3 months prior to screening

You may not qualify if:

• History of liver or renal insufficiency
• Have any ferromagnetic medical implants or medical devices that can be de-programmed by strong magnetic fields such as, but not limited to: cardiac pacemakers, implantable cardiac defibrillators, cochlear implants, or insulin pumps
• Had a surgical intervention on brain or eyes or has an intraocular foreign metallic object
• Has a history of anxiety and claustrophobia

Sponsors & Collaborators

• Janssen R&D Ireland: lead

Study Sites (1)

Unknown Facility

Merksem, Belgium

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Simeprevir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Janssen R&D Ireland Clinical Trial

  Janssen R&D Ireland

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2012
• First Posted: October 16, 2012
• Study Start: October 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: March 28, 2014

Record last verified: 2014-03

Locations

BE (1)