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

July 2, 2009
November 30, 2012
July 2009
November 2009   (final data collection date for primary outcome measure)
  • 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.
To evaluate the effect of steady-state TVR 750 mg every 8hr on the steady-state pharmacokinetics of R- and S-methadone (2 forms of methadone which have a different structure). [ Time Frame: On the day before starting TVR and on day 7. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00933283 on ClinicalTrials.gov Archive Site
  • 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 ]
  • The potential effect of TVR on the pharmacodynamic effects of methadone therapy will be evaluated. [ Time Frame: The 'Short Opiate Withdrawal scale' and the 'Desires for Drugs Questionnaire' will have to be completed 10 times in a period of 14 days. Also the diameter of the pupil of the eye will be measured 14 times in a period of 14 days. ] [ Designated as safety issue: No ]
  • The short-term safety and tolerability of coadministration of TVR and methadone on stable methadone maintenance therapy will be evaluated. [ Time Frame: Safety and tolerability will be followed during 1 month. ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
A Study to Investigate the Potential Interaction Between Telaprevir and Methadone, at Steady-State
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

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.

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.

Interventional
Phase 1
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Healthy Participants
  • 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.
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.
Interventions:
  • Drug: Telaprevir
  • Drug: Methadone
van Heeswijk R, Verboven P, Vandevoorde A, Vinck P, Snoeys J, Boogaerts G, De Paepe E, Van Solingen-Ristea R, Witek J, Garg V. Pharmacokinetic interaction between telaprevir and methadone. Antimicrob Agents Chemother. 2013 May;57(5):2304-9. doi: 10.1128/AAC.02262-12. Epub 2013 Mar 11.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
December 2009
November 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT00933283
CR015931, VX-950-TiDP24-C135
No
Tibotec BVBA
Tibotec BVBA
Vertex Pharmaceuticals Incorporated
Study Director: Tibotec-Virco Virology BVBA Clinical Trial Tibotec BVBA
Tibotec BVBA
November 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP