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

NCT00915564 | Completed Phase 1

• 2 other identifiers: CR015934TMC435-TIDP16-C110
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatitis C

Keywords

Hepatitis C; HCV; Hepatitis C Virus; HCV negative; Protease inhibitor; Methadone; TMC435

Outcome Measures

Primary Outcomes (21)

• Predose plasma concentration of S-methadone

  Day -4 to Day 6

• 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

• 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

• 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

• 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

• 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

• 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

• Predose plasma concentration of R-methadone

  Day -4 to Day 7

• 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

• 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

• 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

• 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

• 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

• 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

• Predose plasma concentration of TMC435

  Day 4 to Day 6

• 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

• 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

• 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

• 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

• 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

• 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

Secondary Outcomes (4)

• Short Opiate Withdrawal Scale Scores

  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

• 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

• Resting pupil diameter

  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

• Number of participants with adverse events as a measure of safety and tolerability

  Up to 30 to 32 days after the last medication dose

Study Arms (1)

TMC435 + methadone

EXPERIMENTAL

Supervised intake of individualized methadone dose (range, 30 to 150 mg once daily) from Day -14 to Day -1; followed by addition of 150 mg dose of TMC435 once daily from Day 1 to Day 7 along with methadone; and later followed by continued intake of individualized methadone 30 to 32 days follow-up.

Drug: TMC435; Other: Methadone

Interventions

TMC435 DRUG

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

TMC435 + methadone

Methadone OTHER

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.

TMC435 + methadone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tibotec Pharmaceuticals, Ireland: lead

Study Sites (1)

Unknown Facility

Toronto, Canada

Location

Related 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

MeSH Terms

Conditions

Hepatitis C

Interventions

Simeprevir; Methadone

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; Ketones

Study Officials

• Tibotec Pharmaceuticals, Ireland Clinical Trial

  Tibotec Pharmaceuticals, 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: June 4, 2009
• First Posted: June 8, 2009
• Study Start: September 1, 2009
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: October 16, 2013

Record last verified: 2013-10

Locations

CA (1)