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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00915564
First received: June 4, 2009
Last updated: October 11, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: TMC435
Other: Methadone
Phase 1

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

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • Predose plasma concentration of S-methadone [ Time Frame: Day -4 to Day 6 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Predose plasma concentration of R-methadone [ Time Frame: Day -4 to Day 7 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Predose plasma concentration of TMC435 [ Time Frame: Day 4 to Day 6 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    Pupillometry will be performed and resting pupil diameter will be assessed with a validated pupillograph.

  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 13
Study Start Date: September 2009
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TMC435 + methadone
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
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.

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00915564

Locations
Canada
Toronto, Canada
Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals, Ireland Clinical Trial Tibotec Pharmaceuticals, Ireland
  More Information

Additional Information:
No publications provided

Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00915564     History of Changes
Other Study ID Numbers: CR015934, TMC435-TIDP16-C110
Study First Received: June 4, 2009
Last Updated: October 11, 2013
Health Authority: Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
Hepatitis C
HCV
Hepatitis C Virus
HCV negative
Protease inhibitor
Methadone
TMC435

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Methadone
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Antitussive Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on September 22, 2014