A Study to Investigate the Potential Interaction Between Telaprevir and Methadone, at Steady-State

This study has been completed.
Sponsor:
Collaborator:
Vertex Pharmaceuticals Incorporated
Information provided by (Responsible Party):
Tibotec BVBA
ClinicalTrials.gov Identifier:
NCT00933283
First received: July 2, 2009
Last updated: November 30, 2012
Last verified: November 2012
  Purpose

The purpose of this study is to evaluate the effect of steady-state (constant concentration of medication in the blood) telaprevir 750 mg every 8 hours on the steady-state pharmacokinetics (how the drug concentrations change over time) of R- and S-methadone.


Condition Intervention Phase
Healthy Participants
Drug: Telaprevir
Drug: 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 Interaction Between Telaprevir 750 mg q8h and Methadone, at Steady-State

Resource links provided by NLM:


Further study details as provided by Tibotec BVBA:

Primary Outcome Measures:
  • Maximum plasma concentration (Cmax) of telaprevir [ Time Frame: On Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmax of telaprevir is measured when telaprevir will be administered at 750 mg every 8 hours for 7 days added to stable methadone maintenance therapy.

  • Minimum plasma concentration (Cmin) of telaprevir [ Time Frame: On Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmin of telaprevir is measured when telaprevir will be administered every 8 hours for 7 days added to stable methadone maintenance therapy.

  • Area under the plasma concentration-time curve (AUC) of telaprevir [ Time Frame: On Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter AUC of telaprevir is measured when telaprevir will be administered every 8 hours for 7 days added to stable methadone maintenance therapy.

  • Cmax of R-methadone [ Time Frame: Day -1 and Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmax of R-methadone is measured during stable methadone maintenance therapy alone and in the presence of steady-state telaprevir at 750 mg every 8 hours.

  • Cmin of R-methadone [ Time Frame: Day -1 and Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmin of R-methadone is measured during stable methadone maintenance therapy alone and in the presence of steady-state telaprevir every 8 hours.

  • AUC of R-methadone [ Time Frame: Day -1 and Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter AUC of R-methadone is measured during stable methadone maintenance therapy alone and in the presence of steady-state telaprevir every 8 hours.

  • Cmax of S-methadone [ Time Frame: Day -1 and Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmax of S-methadone is measured during stable methadone maintenance therapy alone and in the presence of steady-state telaprevir at 750 mg every 8 hours.

  • Cmin of S-methadone [ Time Frame: Day -1 and Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter Cmin of S-methadone is measured during stable methadone maintenance therapy alone and in the presence of steady-state telaprevir every 8 hours.

  • AUC of S-methadone [ Time Frame: Day -1 and Day 7 ] [ Designated as safety issue: No ]
    Pharmacokinetic parameter AUC of S-methadone is measured during stable methadone maintenance therapy alone and in the presence of steady-state telaprevir every 8 hours.


Secondary Outcome Measures:
  • Short Opiate Withdrawal Scale [SOWS] [ Time Frame: Day -7, and Day -2 to Day 7 ] [ Designated as safety issue: Yes ]
    Pharmacodynamic assessments of methadone withdrawal are performed by means of SOWS.

  • Desires for Drugs Questionnaire [DDQ] [ Time Frame: Day -7, and Day -2 to Day 7 ] [ Designated as safety issue: Yes ]
    Pharmacodynamic assessments of methadone withdrawal are performed by means of DDQ.

  • Pupillometry [ Time Frame: Day -1, Day 2, Day 4, and Day 7 ] [ Designated as safety issue: Yes ]
    Pharmacodynamic assessments of methadone withdrawal are performed by means of pupillometry.

  • Number of participants with adverse events [ Time Frame: Up to 60 days ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: July 2009
Study Completion Date: December 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Telaprevir + Methadone
Patients will receive telaprevir 750 mg orally, every 8 hours from Day 1 to Day 7, along with methadone 30 to 130 mg, once daily.
Drug: Telaprevir
Telaprevir 750 mg will be administered orally, every 8 hours from Day 1 to Day 7, along with methadone, once daily.
Drug: Methadone
Methadone 30 to 130 mg will be administered as a stable oral therapy from Day -14 to Day -1, in combination with telaprevir from Day 1 to Day 7, and then alone as a continued intake dose for an additional 30 to 32 days.

Detailed Description:

This is a Phase 1, open-label (all people know the identity of the intervention), single-sequence study to evaluate the potential interaction of steady-state telaprevir on the steady-state pharmacokinetics of methadone. The study consists of 3 phases: the screening phase (within 21 days prior to the start of supervised methadone intake on Day -14), treatment phase, and follow-up phase. Participants on stable methadone maintenance therapy will be enrolled in this study and their methadone doses will not be changed starting at Day -14. During the treatment phase, telaprevir will be added for 7 days (from Day 1 to Day 7) to participants' current methadone therapy. The methadone dosage will not to be changed from Day -14 until Day 7. All the intakes of methadone and telaprevir will be supervised and pharmacokinetic parameters will be measured during the study. Safety evaluations for adverse events, clinical laboratory tests, alcohol breath test, cardiovascular safety, and other evaluations (physical examination, and pharmacodynamic assessments) will be performed throughout the study. The total duration of the study for each participant is approximately 60 days.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Must receive once daily oral methadone maintenance therapy at a stable individualized dose of 30 to 130 mg for at least 2 weeks prior to screening, formulated as commercially available tablets or solution
  • Must agree not to change the current methadone dose from screening until Day 7 included to have a daily observed and documented methadone intake from Day -14 until Day 8 and a daily observed and documented telaprevir intake from Day 1 until Day 7
  • Participants have to obtain approval for participation from his/her addiction physician, and the addiction physician has to agree to provide medical care for the participant after discharge from study center
  • General medical condition must not interfere with the assessments and the completion of the study
  • Health assessments will be done on the basis of physical examination, medical history, electrocardiogram, vital signs and the results of blood biochemistry, blood coagulation and hematology tests and a urinalysis carried out at screening

Exclusion Criteria:

  • History of any illness that could confound the results of the study or pose an additional risk in administering study medication to the participant, for eg, history of relevant medication or food allergies, history of cardiovascular or central nervous system disease, history or presence of clinically significant pathology or history of mental disease
  • Consumption of herbal medications or dietary supplements, vitamins, and grapefruit or grapefruit juice, apple juice or orange juice within 14 days before Day -1
  • Current alcohol use, which, in the assessment of the investigator, could compromise participant's safety or compliance with the study protocol procedures
  • Test positive for drugs of abuse such as cocaine, amphetamines, barbiturates, benzodiazepines, or opiates on Day -2 unless explained by allowed concomitant medications
  • Participation in a clinical study involving administration of an investigational medication within 60 days or 5 half-lives (whichever was longer) prior to the screening visit
  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: NCT00933283

Sponsors and Collaborators
Tibotec BVBA
Vertex Pharmaceuticals Incorporated
Investigators
Study Director: Tibotec-Virco Virology BVBA Clinical Trial Tibotec BVBA
  More Information

Additional Information:
No publications provided by Tibotec BVBA

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tibotec BVBA
ClinicalTrials.gov Identifier: NCT00933283     History of Changes
Other Study ID Numbers: CR015931, VX-950-TiDP24-C135
Study First Received: July 2, 2009
Last Updated: November 30, 2012
Health Authority: Canada: Health Canada

Keywords provided by Tibotec BVBA:
Healthy participants
Pharmacokinetics
Pharmacodynamic
Potential interaction
VX-950-TiDP24-C135
VX-950
Methadone
Telaprevir
Steady-state

Additional relevant MeSH terms:
Methadone
Analgesics
Analgesics, Opioid
Antitussive Agents
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014