A Study to Investigate the Potential Pharmacokinetic Interaction Between TMC435 and Methadone
Information source: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatitis C
Intervention: TMC435 (Drug); Methadone (Other)
Phase: Phase 1
Status: Completed
Sponsored by: Tibotec Pharmaceuticals, Ireland Official(s) and/or principal investigator(s): Tibotec Pharmaceuticals, Ireland Clinical Trial, Study Director, Affiliation: Tibotec Pharmaceuticals, Ireland
Summary
The purpose of this study is to evaluate the effect of steady-state (constant concentration
of medication in the blood) TMC435 (150 mg, once a day) on the steady state pharmacokinetics
(what the body does to the medication) of R- and S-methadone.
Clinical Details
Official title: A Phase I, Open-Label, Single-Sequence Drug-Drug Interaction Trial in Subjects On Stable Methadone Maintenance Therapy, to Investigate the Potential Pharmacokinetic Interaction Between TMC435 and Methadone, at Steady-State
Study design: Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Predose plasma concentration of S-methadoneMaximum plasma concentration of S-methadone Minimum plasma concentration between 0 hour and dosing interval of S-methadone Average steady-state plasma concentration of S-methadone Time to reach the maximum plasma concentration of S-methadone Area under the curve from time of administration up to 24 hours post dosing of S-methadone Fluctuation index of S-methadone, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state) Predose plasma concentration of R-methadone Maximum plasma concentration of R-methadone Minimum plasma concentration between 0 hour and dosing interval of R- and S-methadone Average steady-state plasma concentration of R-methadone Time to reach the maximum plasma concentration of R-methadone Area under the curve from time of administration up to 24 hours post dosing of R-methadone Fluctuation index of R-methadone, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state) Predose plasma concentration of TMC435 Maximum plasma concentration of TMC435 Minimum plasma concentration between 0 hour and dosing interval of TMC435 Average steady-state plasma concentration of TMC435 Time to reach the maximum plasma concentration of TMC435 Area under the curve from time of administration up to 24 hours post dosing of TMC435 Fluctuation index of TMC435, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state)
Secondary outcome: Short Opiate Withdrawal Scale ScoresDesires for Drugs Questionnaire Resting pupil diameter Number of participants with adverse events as a measure of safety and tolerability
Detailed description:
This is an open label (all people know the identity of the intervention) drug-drug
interaction (TMC435 versus methadone) study. Approximately 12 hepatitis C virus-negative
opioid-dependent participants on stable maintenance therapy (for at least 30 days before
screening) will be enrolled in the study. The study will consist of 3 phases: 1) Run-in
phase: during this phase, participants will take individualized (dose of methadone will be
adjusted for each participant between a range of 30 and 150 mg daily) dose of methadone from
Day - 14 (14 days before the first intake of TMC435) till Day -1 (1 day before the first
intake of TMC435), which will be supervised by the medical staff. 2) 7 days treatment phase:
during this phase, the participants will take 150 mg dose of TMC435 once daily from Day 1 to
Day 7 orally (by mouth) plus the individualized dose of methadone which will be supervised
by the medical staff. 3) Follow-up phase: during this phase, the participants will continue
to take only the individualized dose of methadone for 30-32 days. Safety evaluations will
include assessment of adverse events, clinical laboratory tests, cardiovascular safety,
physical examination and alcohol breath test. The total study duration will be of 22 days
excluding screening and follow-up phase.
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Receiving once daily oral methadone maintenance therapy at a stable individualized
dose of 30 to 130 mg once daily for at least 30 days prior to screening
- Agreeing not to change the current methadone dose from screening until Day7 included
and to have a daily observed and documented methadone intake from Day-14 until Day8
and to have a daily observed and documented TMC435 intake from Day1 until Day 7
- Having obtained approval from his/her addiction physician for participation in the
trial and addiction physician agrees to provide medical care for the volunteer after
discharge from the testing facility
Exclusion Criteria:
- No female of childbearing potential, except if using effective birth control methods
during the trial and for at least 30 days after the end of the treatment period
- No positive testing for drugs of abuse
- No positive testing for Hepatitis A, B and C and for HIV1 and 2
- Impaired liver disease or other clinically relevant diseases
Locations and Contacts
Toronto, Canada
Additional Information
A Phase I, Open-Label, Single-Sequence Drug-Drug Interaction Trial in Subjects On Stable Methadone Maintenance Therapy, to Investigate the Potential Pharmacokinetic Interaction Between TMC435 and Methadone, at Steady-State
Starting date: September 2009
Last updated: October 11, 2013
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