TMC125-TiDP2-C188: A Phase I, Open-Label Trial to Investigate the Pharmacokinetic Effect of Multiple-Dose TMC125 on Buprenorphine and Norbuprenorphine Administered in HIV-Negative Patients on Stable Buprenorphine/Naloxone Maintenance Therapy. - Full Text View

Sponsored by:	Tibotec Pharmaceuticals Limited, Ireland
Information provided by:	Tibotec Pharmaceuticals Limited, Ireland
ClinicalTrials.gov Identifier:	NCT00828815

Purpose

TMC125 is from the class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs). NNRTIs work by blocking reverse transcriptase, a protein that HIV needs to make more copies of itself. TMC125 is used in the treatment of adults with HIV-1 infection. The purpose of this trial is to see if there is any potential interaction (change in the effectiveness of the drug) when taking multiple-dose TMC125 and buprenorphine/naloxone together. The trial will also assess the short-term safety and tolerability (how well your body handles the drug) when TMC125 and buprenorphine/naloxone are taken together.

Condition	Intervention	Phase
Pharmacokinetics HIV	Drug: TMC125	Phase I

MedlinePlus related topics: AIDS

Drug Information available for: Naloxone Naloxone hydrochloride Buprenorphine Buprenorphine hydrochloride Etravirine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics Study
Official Title:	A Phase I, Open-Label Trial to Investigate the Pharmacokinetic Effect of Multiple-Dose TMC125 on Buprenorphine and Norbuprenorphine Administered in HIV-Negative Subjects on Stable Buprenorphine/Naloxone Maintenance Therapy.

Further study details as provided by Tibotec Pharmaceuticals Limited, Ireland:

Primary Outcome Measures:

The primary objective is to determine the effect of multiple-dose TMC125 on the steady-state pharmacokinetics of buprenorphine and its metabolite norbuprenorphine in HIV-negative patients during 2 weeks.

Secondary Outcome Measures:

To determine the pharmacokinetics of TMC125, the pharmacodynamic effects of opiate excess or withdrawal and short-term safety and tolerability of the co-administration of TMC125 and buprenorphine/naloxone during 2 weeks of coadministration with TMC125.

Estimated Enrollment:

16

Detailed Description:

This is a Phase I, open-label (patient and trial doctor know what medication you are taking at any point in time during the trial), add-on trial in patients who are on stable sublingual (placed in the mouth under the tongue until it disolves) buprenorphine/naloxone maintenance therapy, to investigate the potential pharmacokinetic effect of multiple-dose TMC125 on buprenorphine and norbuprenorphine administered as buprenorphine/naloxone. The study population will consist of 16 HIV-negative opioid-dependent patients on stable individualized sublingual buprenorphine/naloxone maintenance therapy. Patients will first participate in a 2 weeks run-in period with supervised buprenorphine/naloxone intake. Subsequently, patients will receive TMC125 200 mg orally twice daily for 14 days added to their buprenorphine/naloxone treatment. During the treatment period from Day 1 to Day 14, the individualized buprenorphine/naloxone treatment will be continued with co-administration of TMC125. Full pharmacokinetic profiles of buprenorphine and norbuprenorphine will be determined on Days -1 and 14 up to 24 hours postdose. Full pharmacokinetic profiles of TMC125 will be determined on Day 14 up to 12 hours postdose. Pharmacodynamic assessments of symptoms of opiate withdrawal and excess will be performed. The short-term safety and tolerability will be assessed throughout the trial.

Patients will firstparticipate in a 2 weeks run-in period with supervised buprenorphine/naloxone intake. Subsequently, patients will receive 2 tablets of 100 mg TMC125 twice daily for 14 days added to their buprenorphine/naloxone treatment. During the treatment period from Day 1 to Day 14, the individualized buprenorphine/naloxone treatment will be continued with co-administration of TMC125.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Body Mass Index (BMI) of 18.0 to 30.0 kg/m2, extremes included. BMI is calculated as the weight (in kg) divided by the square of height (in m)
Receiving once daily buprenorphine/naloxone maintenance therapy at a stable individualized dose formulated and administered as sublingual tablets with a maximum daily dose of 16/4 mg of buprenorphine/naloxone. Patients using buprenorphine only are also eligible if they switch to buprenorphine/naloxone minimally 2 weeks before randomization
The patient agrees not to change the current buprenorphine/naloxone therapy from Screening until Day 14 included (switching buprenorphine to buprenorphine/naloxone between Screening and Day -14 is allowed)and to have a daily observed and documented buprenorphine/naloxone intake from Day -14 until Day 15
General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial

Exclusion Criteria:

A positive HIV-1 or HIV-2 test at Screening
Female, except if postmenopausal since more than 2 years, or posthysterectomy, or post-tubal ligation (without reversal operation)
Evidence of current use of barbiturate, amphetamine, recreational or narcotic drug use (cocaine, inhalants, stimulants), sedative hypnotics (benzodiazepines), excessive alcohol or opioids. The drug screening involves analysis for amphetamines, barbiturates, benzodiazepines, cocaine and opioids
Hepatitis A infection (confirmed by hepatitis A antibody IgM), or hepatitis B infection (confirmed by hepatitis B surface antigen) at study screening
Currently active gastrointestinal, cardiovascular, neurologic, psychiatric, metabolic, renal, hepatic, respiratory, inflammatory, or infectious disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00828815

Contacts

Contact: This study is not yet recruiting patients. Please check back for future recruiting sites, or email

info1@veritasmedicine.com

Sponsors and Collaborators

Tibotec Pharmaceuticals Limited, Ireland

Investigators

Study Director:

Tibotec Pharmaceuticals Limited Clinical Trial

Tibotec Pharmaceuticals Limited, Ireland

More Information

Study ID Numbers:	CR015775
Study First Received:	January 22, 2009
Last Updated:	January 22, 2009
ClinicalTrials.gov Identifier:	NCT00828815
Health Authority:	Ireland: Irish Agriculture and Food Development Authority

Keywords provided by Tibotec Pharmaceuticals Limited, Ireland:

TMC125
HIV-negative
buprenorphine/nalaxone
TMC125-TiDP2-C188

opioid-dependent
TMC125-C188
norbuprenorphine

Study placed in the following topic categories:

Buprenorphine
HIV Infections
Acquired Immunodeficiency Syndrome
Naloxone

Additional relevant MeSH terms:

Sensory System Agents
Therapeutic Uses
Narcotic Antagonists
Physiological Effects of Drugs
Central Nervous System Depressants
Narcotics

Peripheral Nervous System Agents
Analgesics
Central Nervous System Agents
Pharmacologic Actions
Analgesics, Opioid

ClinicalTrials.gov processed this record on January 30, 2009