Phase II Amount
$2,022,838
This application addresses Research and Research Infrastructure Grand Opportunities (RC2) (RFA-OD-09-004) priority area: "Small Molecule Development for Substance Related Disorders." Addiction to heroin and prescription opioids represents a worldwide health and social crisis. Over 1.6 million people in the United States (US) and 15 million people globally (0.2% of the global population) are abusing or dependent on opioids. The use of buprenorphine for the treatment of opioid addiction is now well established and accepted as a safe and useful office-based treatment for opioid addiction. Though the daily dosing of sublingual buprenorphine tablets has proven effective, this treatment has several shortcomings that have lead to significant public health concerns. First, patient compliance is low due to the need for frequent dosing, the nature of addictive behavior, and the highly unstable lifestyle of some patients. More specifically, poor medication adherence is the leading cause of relapse, treatment failure, and mortality in this population. In addition to issues with compliance, there is also significant abuse and illicit diversion of the tablet form of buprenorphine, a growing public health issue in the US. Probuphine( (buprenorphine hydrochloride/ethylene vinyl acetate) is a small, subcutaneous, implant formulation of buprenorphine that provides continuous delivery of drug for 6 months following a single treatment, and is under Phase 3 clinical development for the treatment of opioid addiction. Previous studies with Probuphine( have shown that it offers the same benefits as sublingual buprenorphine, but potentially eliminates two of the biggest problems with sublingual tablets: poor adherence and diversion. In order to meet FDA requirements, and for Probuphine( to become available to patients, an additional placebo-controlled trial must be completed. This six-month study will compare the safety and effectiveness of Probuphine( to placebo and also to the sublingual tablet form of buprenorphine, Suboxone(. It will be conducted in approximately 20 addiction treatment centers across the US, with a target enrollment of 250 participants. Successful screeners will be randomized in a 2:1:2 ratio to receive Probuphine( implants, placebo implants, or sublingual buprenorphine (12-18mg/day). All participants will also receive standardized (manual-driven), individual weekly drug counseling. Participants will be seen thrice weekly for the first 16 weeks and weekly for the last 8 weeks, followed by one additional safety visit at week 25. The primary specific aim is to compare the proportion of opioid-negative urine samples between groups at week 16. Secondary specific aims include evaluation of other important clinical parameters of addiction treatment including withdrawal symptoms, drug craving, and treatment compliance. This study will begin and complete within the 2-year time frame allowed.
Public Health Relevance: Despite the well-established effectiveness and safety of sublingual buprenorphine (Suboxone() in the treatment of opioid addiction, significant therapeutic and public health issues exist due to poor medication adherence, and diversion and misuse of the sublingual tablets. This research project will evaluate an innovative new treatment, Probuphine(, which is a subcutaneous implant formulation of buprenorphine that delivers medication for six months following a single treatment. The significance of this research is that once approved and available to patients, Probuphine( will substantially address the important public health issues of compliance to treatment and diversion.
Public Health Relevance Statement: Project narrative: A six-month, RCT of Probuphine(R) safety and efficacy in opioid addiction Despite the well-established effectiveness and safety of sublingual buprenorphine (Suboxone) in the treatment of opioid addiction, significant therapeutic and public health issues exist due to poor medication adherence, and diversion and misuse of the sublingual tablets. This research project will evaluate an innovative new treatment, Probuphine, which is a subcutaneous implant formulation of buprenorphine that delivers medication for six months following a single treatment. The significance of this research is that once approved and available to patients, Probuphine will substantially address the important public health issues of compliance to treatment and diversion.
NIH Spending Category: Behavioral and Social Science; Brain Disorders; Clinical Research; Clinical Trials; Comparative Effectiveness Research; Neurosciences; Prescription Drug Abuse; Substance Abuse
Project Terms: active control; addiction; Addictive Behavior; Address; Adherence (attribute); Area; base; Buprenorphine; Clinical; clinical research site; Compliance behavior; Counseling; Data; Data Analyses; Data Quality; Development; Dose; drug craving; Drug Delivery Systems; Drug Formulations; effective therapy; Effectiveness; Enrollment; Ethylenes; Evaluation; experience; Funding; Generations; Goals; Grant; Health; Health Benefit; Heroin; Hydrochloride Salt; Implant; Individual; innovation; Lead; Life Style; Manuals; Measures; Medical; medication compliance; meetings; minority subjects; Mortality Vital Statistics; Nature; Opiate Addiction; Opioid; Participant; Patients; Pharmaceutical Preparations; Phase; phase 3 study; placebo controlled study; Placebos; Population; Preparation; prescription opioid; Process; Product Approvals; Program Development; programs; Public Domains; public health medicine (field); public health relevance; Randomized; Relapse; Relative (related person); Reporting; Research; Research Infrastructure; Research Project Grants; Safety; Sampling; small molecule; social; subcutaneous; Substance-Related Disorders; Symptoms; Tablets; Therapeutic; Therapeutic Effect; therapy development; Time; treatment center; Treatment Failure; United States; Urine; vinyl acetate; Visit; Withdrawal Symptom; Woman
