TMC278-TiDP6-C121: Drug-drug Interaction Trial to Investigate the Potential Interaction Between TMC278 25 mg Daily and Methadone, at Steady State.

This study has been completed.
Sponsor:
Information provided by:
Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:
NCT00744770
First received: August 29, 2008
Last updated: April 26, 2010
Last verified: April 2010
  Purpose

The purpose of this Phase I, open-label, single-sequence drug-drug interaction trial in patients on stable methadone maintenance therapy is to investigate the potential interaction between TMC278 25 mg daily and methadone, at steady-state.


Condition Intervention Phase
HIV
Drug: TMC278
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics 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 TMC278 25 mg q.d. and Methadone, at Steady-state.

Resource links provided by NLM:


Further study details as provided by Tibotec Pharmaceuticals, Ireland:

Primary Outcome Measures:
  • To evaluate the effect of steady-state TMC278 25 mg q.d. on the steady-state pharmacokinetics of R- and S-methadone after 11 days of TMC278 intake.

Secondary Outcome Measures:
  • To evaluate after 11 days of TMC278 intake: the potential effect of TMC278 on the pharmacodynamic effects of methadone therapy; the steady-state pharmacokinetics of TMC278 25 mg daily; the short-term safety and tolerability of coadministration.

Enrollment: 13
Study Start Date: October 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Detailed Description:

This is a Phase I, open-label, single-sequence drug-drug interaction trial in patients on stable methadone maintenance therapy, to investigate the potential interaction between TMC278 25 mg daily and methadone, at steady-state. TMC278 is under development for the treatment of HIV-1 infected patients. The trial population will consist of 16 HIV-negative patients on stable methadone maintenance therapy. Patients will receive TMC278 25 mg daily for 11 days, added to their current methadone therapy. The current methadone dosage for each patient is not to be changed from screening until Day 11 inclusive. Methadone dose will be individualized for each patient and should be between 60 and 150 mg daily. Full 24 hour pharmacokinetic profiles of R- and S-methadone will be determined on Day -1 (methadone alone) and on Day 11 (methadone + TMC278). A full 24 hour pharmacokinetic profile of TMC278 will be determined on Day 11 (methadone + TMC278). Pharmacodynamic assessments of the symptoms of methadone withdrawal (Short Opiate Withdrawal Scale (SOWS), Desires for Drugs Questionnaire (DDQ), pupillometry) will be performed on Day -7 and daily from Day -3 until Day 11, within 2 hours before the intake of methadone. Safety and tolerability will be evaluated continuously throughout the trial. Patients will receive TMC278 added to their current methadone therapy in the following way: methadone individualized maintenance therapy, 60 to 150 mg daily from Day -14 to 11 and TMC278 25 mg tablet by mouth daily from Day 1 to 11. TMC278 and methadone will both be taken within 10 minutes after completion of a breakfast.

  Eligibility

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

Inclusion Criteria:

  • Body Mass Index of 18.0 to 30.0 kg/m2, extremes included
  • Receiving once daily oral methadone maintenance therapy at a stable individualized dose of 60 to 150 mg
  • The patient agrees not to change the current methadone dose from screening until Day 11 included and to have a daily observed and documented methadone intake from Day -14 until Day 12, and a daily observed and documented TMC278 intake from Day 1 until Day 11
  • Able to comply with protocol requirements
  • The patient has obtained approval from his/her addiction physician for participation in this trial. Furthermore, the addiction physician agrees to provide medical care for the patient after discharge from the testing facility
  • General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial
  • Otherwise healthy on the basis of a physical examination, medical history (except drug abuse), ECG, vital signs and the results of blood biochemistry and hematology tests and a urinalysis carried out at screening.

Exclusion Criteria:

  • A positive test for HIV-1, HIV-2, hepatitis A virus or hepatitis B virus
  • female of child bearing potential
  • evidence of current use of illicit drugs or opioids (with the exception of methadone) or abuse of alcohol
  • impaired liver function as defined in the protocol
  • other currently active or underlying disorders, including gastrointestinal, cardiovascular, neurologic, psychiatric (other than drug dependency), metabolic, adrenal, renal, hepatic, respiratory, inflammatory, or infectious disease
  • presence of risk factors for QTc prolongation
  • any history of significant skin disease or allergies, including allergy or hypersensitivity to the excipients of the investigational medication TMC278 or to methadone
  • Previous experience of clinically significant hypersensitivity to methadone hydrochloride
  • Use of disallowed concomitant therapy during the 14 days prior to the first dose of TMC278
  • recent donation of blood or plasma or participation in a clinical trial.
  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: NCT00744770

Sponsors and Collaborators
Tibotec Pharmaceuticals, Ireland
Investigators
Study Director: Tibotec Pharmaceuticals Limited Clinical Trial Tibotec Pharmaceutical Limited
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00744770     History of Changes
Other Study ID Numbers: CR002524
Study First Received: August 29, 2008
Last Updated: April 26, 2010
Health Authority: Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals, Ireland:
TMC278-TiDP6-C121
TMC278-C121
open-label
drug-drug interaction
methadone
TMC278

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 23, 2014