Extension to Safety and Efficacy of Probuphine in the Treatment of Opioid Dependence

Study Overview
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Brief Summary
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Buprenorphine (BPN) is an approved treatment for opioid dependence; however, in taking oral tablets, patients experience withdrawal and cravings when the variable BPN levels in the blood are low. Probuphine (buprenorphine implant) is an implant placed just beneath the skin that contains BPN. It is designed to provide 6 months of stable BPN blood levels. This study will test the safety and efficacy of Probuphine in the treatment of patient with opioid dependence. Patients who have completed 24 weeks of treatment in the Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of Probuphine in Patients with Opioid Dependence, will be re-treated with Probuphine over an additional 24 weeks.

Official Title
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An Open-Label, Multi-Center Extension Study Of Probuphine in Patients With Opioid Dependence

Conditions
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Opioid Dependence

Intervention / Treatment
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* Drug: Probuphine (buprenorphine implant)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily provide written informed consent prior to conduct of any study-related procedures Completed 24 weeks of treatment in PRO-805 Deemed appropriate for entry into this extension study by the Investigator Females of childbearing potential and fertile males must use a reliable means of contraception Exclusion Criteria: Presence of aspartate aminotransferase (AST) levels ≥ 3 X upper limit of normal and/or alanine aminotransferase (ALT) levels ≥ 3 X upper limit of normal and/or total bilirubin ≥ 1.5 X upper limit of normal and/or creatinine ≥ 1.5 X upper limit of normal Current diagnosis of chronic pain requiring opioids for treatment Pregnant or lactating females 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 anti-coagulant therapy (such as warfarin) or an INR > 1.2 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 Investigator, 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probuphine<br>buprenorphine implant | Drug: Probuphine (buprenorphine implant)<br>* Implantable formulation of buprenorphine made of buprenorphine HCl/ethylene vinyl acetate, considered a drug. (4 implants, 6-month duration).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety | Adverse events that occurred after the signing of the informed consent until 14 days after study drug treatment has been discontinued, or AEs designated as possibly-related to study drug and all Serious AEs until resolution or stabilization, were followed. | approx. 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Buprenorphine concentration in plasma |  | 24 weeks | 
| Percent of urine samples that are negative for illicit opioids |  | 24 weeks | 
| Percent of subjects retained as a measure of efficacy |  | 24 weeks | 
| Percent of subjects reporting illicit drug use as a measure of efficacy |  | 24 weeks | 
| Average daily dose of supplemental sublingual buprenorphine as a measure of efficacy |  | 24 weeks | 
| Mean total score on SOWS as a measure of efficacy |  | 24 weeks | 
| Mean total score on COWS as a measure of efficacy |  | 24 weeks | 
| Mean subjective opioid cravings scores as a measure of efficacy |  | 24 weeks | 
| Mean composite score Drug Problems area of Addiction Severity Index |  | Baseline and End of Treatment | 
| Patient-rated Opioid use and Problems Responder Analysis as a measure of efficacy |  | 24 weeks | 
| Physician-rated severity of opioid use and symptoms Responder Analysis as a measure of efficacy |  | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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opioid dependence, opioid addiction, buprenorphine, methadone, heroin, implant, opioid withdrawal, opioid pain medication, suboxone