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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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01707342
First Posted: October 16, 2012
Last Update Posted: March 28, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Janssen R&D Ireland
  Purpose
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.

Condition Intervention Phase
Healthy Male Participants Drug: Simeprevir (TMC435) Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Sequential, Single-Dose Study to Assess the Absolute Bioavailability and Pharmacokinetics of TMC435 Administered as Single Oral Doses of 50 mg and 150 mg and an Intravenous Microdose of 100 μg [3H]-TMC435 in Healthy Male Subjects

Resource links provided by NLM:


Further study details as provided by Janssen R&D Ireland:

Primary Outcome Measures:
  • Absolute bioavailability of simeprevir (TMC435) [ Time Frame: Pre-dose Day 1, post-dose Days 1-4 ]
  • Volume of distribution of [3H]-TMC435 and [3H]-total radioactivity [ Time Frame: Pre-dose Day 1, post-dose Days 1-4 ]
  • Maximum observed plasma concentration of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Pre-dose Day 1, post-dose Days 1-4 ]
  • Mean residence time of [3H]-TMC435 and [3H]-total radioactivity [ Time Frame: Pre-dose Day 1, post-dose Days 1-4 ]
  • Terminal elimination rate constant of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity [ Time Frame: Pre-dose Day 1, post-dose Days 1-4 ]
  • Terminal elimination half-life of simeprevir (TMC435), [3H]-TMC435, and [3H]-total radioactivity [ Time Frame: 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 [ Time Frame: Pre-dose Day 1, post-dose Days 1-4 ]

Secondary Outcome Measures:
  • Total radioactivity excreted into the feces from time 0 to the time of discharge [ Time Frame: Post-dose Hours 5, 24, 48, 72, and 96 ]
  • Total radioactivity excreted into the feces expressed as a percentage of the administered dose [ Time Frame: Post-dose Hours 5, 24, 48, 72, and 96 ]
  • Total radioactivity excreted into urine from time 0 to the time of discharge [ Time Frame: Post-dose Hours 5, 24, 48, 72, and 96 ]
  • Total radioactivity excreted into the urine expressed as a percentage of the administered dose [ Time Frame: Post-dose Hours 5, 24, 48, 72, and 96 ]
  • Number of participants with adverse events [ Time Frame: up to 30 days after dose of study medications ]

Enrollment: 6
Study Start Date: October 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Simeprevir (TMC435)
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)
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.

Detailed Description:
This is an open-label (all people know the identity of the intervention), sequential (a single group of participants where study medication is administered in a sequence), single-dose study to assess the absolute bioavailability and pharmacokinetics (what the body does to the medication) of single oral doses of 50 mg and 150 mg simeprevir (TMC435) administered together with an intravenous (IV) microdose of 100 microgram [3H]-TMC435 in healthy male participants. The study consists of 3 phases, screening phase (21 days prior to administration of study medication), treatment phase, and a follow up phase. In the treatment phase, participants will receive 2 treatments, ie, Treatment A: single oral dose of simeprevir (TMC435) 50 mg followed 5 hours later by a single 10 minute IV infusion of [3H]-TMC435 (100 microcurie) 100 microgram; and Treatment B: single oral dose of simeprevir (TMC435) 150 mg followed 5 hours later by a single 10 minute IV infusion of [3H]-TMC435 (100 microcurie) 100 microgram. Treatments will be administered in two consecutive treatment periods, first Treatment A in Period 1, followed by Treatment B in Period 2; separated by a washout period (period when the participant is not receiving any study medication) of 7 to 14 days. The follow up will be for 5 to 7 days after end of Period 2. Blood samples will be collected for full plasma pharmacokinetics evaluations; along with urine and stool samples for analysis of total plasma radioactivity. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, physical examination, liver volume determination, and specific toxicities will be monitored throughout the study. The total duration of the study will be approximately 42 days.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01707342


Locations
Belgium
Merksem, Belgium
Sponsors and Collaborators
Janssen R&D Ireland
Investigators
Study Director: Janssen R&D Ireland Clinical Trial Janssen R&D Ireland
  More Information

Responsible Party: Janssen R&D Ireland
ClinicalTrials.gov Identifier: NCT01707342     History of Changes
Other Study ID Numbers: CR100901
TMC435-TiDP16-C118 ( Other Identifier: Janssen R&D Ireland )
2012-002330-37 ( EudraCT Number )
First Submitted: October 12, 2012
First Posted: October 16, 2012
Last Update Posted: March 28, 2014
Last Verified: March 2014

Keywords provided by Janssen R&D Ireland:
Healthy male participants
Absolute bioavailability
Bioavailability
Pharmacokinetics
Simeprevir
TMC435
[3H]-TMC435
Hepatitis C virus
HCV

Additional relevant MeSH terms:
Simeprevir
Antiviral Agents
Anti-Infective Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action