A Six-Month Randomized Controlled Trial (RCT) of Probuphine Safety and Efficacy in Opioid Addiction

Study Overview
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Brief Summary
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Probuphine (buprenorphine implant) is an implant placed just below the skin containing buprenorphine (BPN). BPN is an approved treatment for opioid dependence. This study will confirm the efficacy of Probuphine vs. placebo and compare Probuphine treatment verses treatment with sublingual buprenorphine in the treatment of patients with opioid dependence.

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

Conditions
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Opioid Dependency

Intervention / Treatment
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* Drug: Probuphine (buprenorphine implant)
* Drug: placebo implant
* Drug: Buprenorphine


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-TR criteria for current opioid dependence Females of childbearing potential or a fertile male, must use a reliable means of contraception Exclusion Criteria: Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS) Received any medication-assisted treatment for opioid dependence (e.g., methadone, BPN) within the previous 90 days Current diagnosis of chronic pain requiring opioids for treatment Candidates for short-term opioid treatment (<6 months) only, or opioid detoxification therapy Pregnant or lactating female? Previous hypersensitivity or allergy to BPN, 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), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir) History of coagulopathy within the past 90 days, and/or current anti-coagulant therapy such as warfarin Meet the DSM-IV-TR criteria for dependence on any other psychoactive substances other than opioids or nicotine (e.g., alcohol, sedatives) Significant medical or psychiatric symptoms, cognitive impairment, or other factors which in the opinion of the Investigator would preclude compliance with the protocol, subject safety, adequate cooperation in the study, or obtaining informed consent Current medical conditions such as severe respiratory insufficiency that may prevent the subject from safely participating in study, or any pending legal action that could prohibit participation or compliance in the study Exposure to any investigational drug within the previous 8 weeks Previous exposure to Probuphine, or prior implantation with a placebo implant in the context of a Probuphine clinical trial Presence of aspartate aminotransferase (AST) levels greater than or equal to 3 X the upper limit of normal, alanine aminotransferase (ALT) levels greater than or equal to 3 X the upper limit of normal, total bilirubin greater than or equal to 1.5 X the upper limit of normal, or creatinine greater than 1.5 X upper limit of normal on the screening laboratory assessments Clinically significant low platelet count on the screening laboratory assessments

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probuphine<br>Patients are first inducted on SL BPN then switched to 4 buprenorphine implants | Drug: Probuphine (buprenorphine implant)<br>* Implantable formulation of buprenorphine made of buprenorphine HCl/ethylene vinyl acetate, considered a drug.<br>|
| Placebo Comparator: placebo implant<br>patients are first inducted on SL BPN then switched to 4 placebo implants | Drug: placebo implant<br>* Implant contains ethylene vinyl acetate<br>|
| Active Comparator: sublingual buprenorphine<br>patients are inducted on SL BPN, then continue on SL BPN | Drug: Buprenorphine<br>* sublingual buprenorphine/naloxone tablets<br>* Other names: Suboxone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CDF of the percent of urine samples negative for opioids in Probuphine and Placebo groups from weeks 1-24 |  | 1-24 weeks | 
| CDF of the percent of urine samples negative for opioids from weeks 1-24 with imputation based on illicit drug use self-report data for Probuphine and placebo groups |  | 1-24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CDF of the percent of urine samples negative for opioids from weeks 1-16 |  | 1-16 weeks | 
| CDF of the percent of urine samples negative for opioids from weeks 17-24 |  | 17-24 weeks | 
| Difference of proportion of urine samples negative for illicit opioids over 24 weeks of treatment for Probuphine vs. SL BPN |  | 24 weeks | 

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