A Study to Investigate the Potential Pharmacokinetic Interaction Between TMC435 and Methadone

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00915564
• Other study ID #: CR015934
• Secondary ID: TMC435-TIDP16-C1
• Status: Completed
• Phase: Phase 1
• First received: June 4, 2009
• Last updated: October 11, 2013
• Start date: September 2009
• Est. completion date: January 2010

Study information

• Verified date: October 2013
• Source: Tibotec Pharmaceuticals, Ireland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ireland: Irish Agriculture and Food Development Authority
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• TMC435
Participants will receive 150 mg dose of TMC435 orally (by mouth) once daily for 7 days of treatment (from Day 1 to Day 7).

Other:
• Methadone
Participants will receive supervised individualized methadone dose (dose of methadone will be adjusted for each participant between a range of 30 and 150 mg daily [extremes included]) from Day -14 untill Day 8. Participants will continue to receive individualized methadone during follow up of 30 to 32 days.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tibotec Pharmaceuticals, Ireland

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Predose plasma concentration of S-methadone		Day -4 to Day 6	No
Primary	Maximum plasma concentration of S-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Minimum plasma concentration between 0 hour and dosing interval of S-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Average steady-state plasma concentration of S-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Time to reach the maximum plasma concentration of S-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Area under the curve from time of administration up to 24 hours post dosing of S-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Fluctuation index of S-methadone, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state)		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Predose plasma concentration of R-methadone		Day -4 to Day 7	No
Primary	Maximum plasma concentration of R-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Minimum plasma concentration between 0 hour and dosing interval of R- and S-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Average steady-state plasma concentration of R-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Time to reach the maximum plasma concentration of R-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Area under the curve from time of administration up to 24 hours post dosing of R-methadone		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Fluctuation index of R-methadone, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state)		On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose	No
Primary	Predose plasma concentration of TMC435		Day 4 to Day 6	No
Primary	Maximum plasma concentration of TMC435		On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose	No
Primary	Minimum plasma concentration between 0 hour and dosing interval of TMC435		On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose	No
Primary	Average steady-state plasma concentration of TMC435		On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose	No
Primary	Time to reach the maximum plasma concentration of TMC435		On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose	No
Primary	Area under the curve from time of administration up to 24 hours post dosing of TMC435		On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose	No
Primary	Fluctuation index of TMC435, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state)		On Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose and on Day 8 at 24 hour postdose	No
Secondary	Short Opiate Withdrawal Scale Scores	Short Opiate Withdrawal Scale is used for the assessment of opioid withdrawal. It consists of 10 items and items are designed to measure symptoms, on a scale from 0 to 3 (0= None, 1= Mild, 2= Moderate, 3= Severe). The total score ranges from 0 (best) to 30 (worst). Higher scores indicate worsening.	On Day-1 and Day 7 at 2 hour and 4 hour predose; on Day-7, Day-2, and Day 1 to Day 6 at predose	No
Secondary	Desires for Drugs Questionnaire		On Day-1 and Day 7 at 2 hour and 4 hour predose; on Day-7, Day-2, and Day 1 to Day 6 at predose	No
Secondary	Resting pupil diameter	Pupillometry will be performed and resting pupil diameter will be assessed with a validated pupillograph.	On Day-1 and Day 7 at 2 hour and 4 hour predose; on Day-7, Day-2, and Day 1 to Day 6 at predose	No
Secondary	Number of participants with adverse events as a measure of safety and tolerability		Up to 30 to 32 days after the last medication dose	Yes

External Links

•   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