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 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 patients with opioid dependence.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of Probuphine in Patients With Opioid Dependence

Conditions
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Opioid Dependence

Intervention / Treatment
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* Drug: Probuphine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily provide written informed consent prior to the conduct of any study related procedures Male or female, 18-65 years of age Meet 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) 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 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 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 Meet 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 or dementia 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

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br> | Drug: Probuphine<br>* 4 implants<br>|
| Placebo Comparator: Group B<br> | Drug: placebo<br>* 4 implants<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The cumulative distribution function (CDF) of the percent of urine samples negative for illicit opioids |  | weeks 1-16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The cumulative distribution function (CDF) of the percent of urine samples negative for illicit opioids |  | weeks 17-24 | 
| Mean percent urines negative for illicit opioids |  | weeks 1-16 | 
| Mean percent urines negative for illicit opioids |  | weeks 17-24 | 
| Proportion (percent) of study completers |  | weeks 1-16 | 
| Proportion (percent) of study completers |  | weeks 17-24 | 
| Total number of weeks of abstinence |  | weeks 1-16 | 
| Total number of weeks of abstinence |  | weeks 17-24 | 
| Mean maximal period in weeks of continuous abstinence |  | weeks 1-16 | 
| Mean maximal period in weeks of continuous abstinence |  | weeks 17-24 | 
| Mean total score on the SOWS |  | weeks 1-16 | 
| Mean total score on the SOWS |  | weeks 17-24 | 
| Mean total score on the COWS |  | weeks 1-16 | 
| Mean total score on the COWS |  | weeks 17-24 | 
| Mean subjective opioid cravings assessment (VAS) |  | weeks 1-16 | 
| Mean subjective opioid cravings assessment (VAS) |  | weeks 17-24 | 
| Patient-rated Clinical Global Impression |  | weeks 1-16 | 
| Patient-rated Clinical Global Impression |  | weeks 17-24 | 
| Physician-rated Clinical Global Impression |  | weeks 1-16 | 
| Physician-rated Clinical Global Impression |  | weeks 17-24 | 

 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