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Completed

NCT Number: NCT00915564

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

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.

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Key information

Conditions

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

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Toronto, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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).

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.

Primary outcomes

  1. Predose plasma concentration of S-methadone

    Time frame: Day -4 to Day 6

  2. Maximum plasma concentration of S-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  3. Minimum plasma concentration between 0 hour and dosing interval of S-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  4. Average steady-state plasma concentration of S-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  5. Time to reach the maximum plasma concentration of S-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  6. Area under the curve from time of administration up to 24 hours post dosing of S-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  7. Fluctuation index of S-methadone, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state)

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  8. Predose plasma concentration of R-methadone

    Time frame: Day -4 to Day 7

  9. Maximum plasma concentration of R-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  10. Minimum plasma concentration between 0 hour and dosing interval of R- and S-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  11. Average steady-state plasma concentration of R-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  12. Time to reach the maximum plasma concentration of R-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  13. Area under the curve from time of administration up to 24 hours post dosing of R-methadone

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  14. Fluctuation index of R-methadone, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state)

    Time frame: On Day -1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8 and 12 hours postdose

  15. Predose plasma concentration of TMC435

    Time frame: Day 4 to Day 6

  16. Maximum plasma concentration of TMC435

    Time frame: 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

  17. Minimum plasma concentration between 0 hour and dosing interval of TMC435

    Time frame: 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

  18. Average steady-state plasma concentration of TMC435

    Time frame: 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

  19. Time to reach the maximum plasma concentration of TMC435

    Time frame: 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

  20. Area under the curve from time of administration up to 24 hours post dosing of TMC435

    Time frame: 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

  21. Fluctuation index of TMC435, ie, percentage fluctuation (variation between maximum and minimum concentration at steady-state)

    Time frame: 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

  1. Short Opiate Withdrawal Scale Scores

    Time frame: 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

    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.

  2. Desires for Drugs Questionnaire

    Time frame: 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

  3. Resting pupil diameter

    Time frame: 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

    Pupillometry will be performed and resting pupil diameter will be assessed with a validated pupillograph.

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

    Time frame: Up to 30 to 32 days after the last medication dose

Sponsors and collaborators

Lead sponsor

Tibotec Pharmaceuticals, Ireland

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2010
Study completion
2010
First posted
Jun 8, 2009
Registry last updated
Oct 16, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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