A Bioavailability and Safety Study of Probuphine Versus Sublingual Buprenorphine in Patients With Opioid Dependence

Condition(s) targeted: Opioid Dependence

Intervention: Probuphine (Drug); Sublingual Buprenorphine (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Titan Pharmaceuticals

This study will measure the amount of buprenorphine found in the blood after taking sublingual buprenorphine tablets versus after implantation with 4 Probuphine implants.

Official title: A Single Cross-Over, Open-Label Study of the Relative Bioavailability of Probuphine Versus Buprenorphine Sublingual Tablets at Steady State in Patients With Opioid Dependence

Study design: Treatment, Non-Randomized, Open Label, Crossover Assignment, Bio-availability Study

Primary outcome: To assess the relative bioavailability of Probuphine versus SL BPN as determined by plasma BPN AUC(0-24)during 24 hours at steady state.

Secondary outcome:

To evaluate the pharmacokinetics of buprenorphine released by Probuphine in patients with opioid dependence over 24 weeks of treatment

To assess the inter-patient variability in plasma BPN and NorBPN AUC(0-24) for Probuphine and SL BPN during 24 hours at steady state

To assess maximum plasma BPN and NorBPN concentrations (Cmax) and time to maximum plasma BPN and NorBPN concentration (tmax) and steady stated plasma BPN and Nor BPN concentration (Css) for Probuphine and SL BPN.

To assess the safety and tolerability of Probuphine

Detailed description: This is an open-label study intended to evaluate the relative bioavailability of 4 Probuphine implants versus 16mg QD sublingual buprenorphine, as determined by plasma BPN AUC(0-24), during 24 hours at steady state. This study will also provide open-label safety and tolerability data in patients treated with Probuphine.

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Voluntarily provide written informed consent prior to the conduct of any study related

procedures

- Male or female, 18-75 years of age

- Meet the DSM-IV criteria for current opioid dependence

- Females of childbearing potential and fertile males must use a reliable means of

contraception

Exclusion Criteria:

- Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS)

- Received treatment for opioid dependence (e. g., methadone, BPN) within the previous 90

days

- Current diagnosis of chronic pain requiring opioids for treatment

- Candidates for only short term opioid treatment or opioid detoxification therapy

- Pregnant or lactating females

- Previous hypersensitivity or allergy to BPN or EVA-containing substances or naloxone

- Current use of agents metabolized through Cytochrome P450 3A4 (CYP 3A4) such as azole

antifungals (e. g., ketoconazole), macrolide antibiotics (e. g., erythromycin), and protease inhibitors (e. g., ritonavir, indinavir, and saquinavir)

- Current history of coagulopathy, and/or anti-coagulant therapy (such as warfarin)

- Meet the DSM-IV criteria for current dependence on any other psychoactive substances

other than opioids or nicotine (e. g., alcohol, sedatives)

- Current use of benzodiazepines other than physician prescribed use

- Significant medical or psychiatric symptoms, cognitive impairment, or other factors

which in the opinion of the Investigators would preclude compliance with the protocol, patient safety, adequate cooperation in the study, or obtaining informed consent

- Concurrent medical conditions (such as severe respiratory insufficiency) that may

prevent the patient from safely participating in study; and/or any pending legal action that could prohibit participation and/or compliance in study

- Participated in a clinical study within the previous 8 weeks

- Previous participation in a Probuphine clinical trial

- Presence of aspartate aminotransferase (AST) levels greater than or equal to 3 X upper

limit of normal and/or alanine aminotransferase (ALT) levels greater than or equal to 3 X upper limit of normal and/or total bilirubin greater than or equal to 1. 5 X upper limit of normal and/or creatinine greater than or equal to 1. 5 X upper limit of normal

- Clinically significant low platelet count with current history of coagulopathy

Segal Institute For Clinical Research, Fort Lauderdale, Florida 33308, United States; Recruiting
Lilia Aleman, Phone: 1-877-SEGAL-88

Starting date: September 2008
Ending date: April 2009
Last updated: October 7, 2008