Safety and Efficacy of Probuphine in the Treatment of Opioid Dependence

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

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.

Study Overview

• Status: Completed
• Conditions: Opioid Dependence
• Intervention / Treatment: Drug: Probuphine; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • David Geffen School of Medicine at UCLA
    • National City, California, United States, 91950
      • Synergy Clinical Research Center
    • Oceanside, California, United States, 92056
      • North County Clinical Research
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Amit Vijapura, MD and Associates
    • Lauderhill, Florida, United States, 33319
      • Fidelity Clinical Research
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Northwest Behavioral Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Behavioral Biology Research Unit, Johns Hopkins Bayview Campus
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720-6009
      • Dual Diagnosis Unit, SSTAR: Stanley Street Treatment and Resources, Inc.
  • Michigan
    • Detroit, Michigan, United States, 48207
      • Wayne State University Department of Psychiatry and Behavioral Neurosciences
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Psych Care Consultants Research
  • New York
    • New York, New York, United States, 10010
      • New York VA Medical Center, NYU School of Medicine
    • New York, New York, United States, 10019
      • Addiction Institute of New York
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center Addictions Program
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73118
      • Pahl Pharmaceutical Research, LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Treatment Research Center
  • Washington
    • Everett, Washington, United States, 98206
      • Providence Behavioral Health Services
    • Seattle, Washington, United States, 98108
      • Puget Sound Health Care Systems

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Group B	Drug: placebo; 4 implants
Active Comparator: Group A	Drug: Probuphine; 4 implants

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Titan Pharmaceuticals

Publications and helpful links

General Publications

• Ling W, Casadonte P, Bigelow G, Kampman KM, Patkar A, Bailey GL, Rosenthal RN, Beebe KL. Buprenorphine implants for treatment of opioid dependence: a randomized controlled trial. JAMA. 2010 Oct 13;304(14):1576-83. doi: 10.1001/jama.2010.1427.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: March 12, 2007
• First Submitted That Met QC Criteria: March 12, 2007
• First Posted (Estimate): March 14, 2007

Study Record Updates

• Last Update Posted (Actual): December 31, 2018
• Last Update Submitted That Met QC Criteria: December 27, 2018
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: buprenorphine; opioid dependence; methadone; opioid addiction; implant; heroin; suboxone; opioid pain medication; opioid withdrawal
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: PRO-805