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

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

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.

Study Overview

• Status: Completed
• Conditions: Opioid Dependency
• Intervention / Treatment: Drug: Probuphine (buprenorphine implant); Drug: placebo implant; Drug: Buprenorphine

• Study Type: Interventional
• Enrollment (Actual): 287
• 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
    • Torrance, California, United States, 90502
      • Friends Research Institute
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Amit Vijapura, MD
    • Largo, Florida, United States, 33771
      • Operation PAR, Inc. - TC Campus
    • Lauderhill, Florida, United States, 33319
      • Fidelity Clinical Research, Inc.
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc.
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • BPRU, Behavioral Biology Research Center
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720-6009
      • SSTAR: Stanley Street Treatment and Resources, Inc.
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • PsychCare 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, 10025
      • St. Luke's Roosevelt Hospital Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University, Duke Addictions Program
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Carolina Clinical Trials, Inc.
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Washington
    • Everett, Washington, United States, 98201
      • Providence Behavioral Health Services

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-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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	Time Frame
Percent urines negative for illicit opioids	24 weeks
Percent of study completers	24 weeks
Mean total score on the SOWS	24 weeks
Mean total score on the COWS	24 weeks
Mean subjective opioid craving assessment using Visual Analog Scale (VAS)	24 weeks
Patient-rated Clinical Global Improvement (CGI)	24 weeks
Physician-rated Clinical Global Improvement (CGI)	24 weeks
Mean total number of weeks of abstinence	24 weeks
Mean maximum period of continuous abstinence	24 weeks

Collaborators and Investigators

• Sponsor: Titan Pharmaceuticals
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Katherine L. Beebe, Ph.D., Titan Pharmaceuticals

Publications and helpful links

General Publications

• Rosenthal RN, Ling W, Casadonte P, Vocci F, Bailey GL, Kampman K, Patkar A, Chavoustie S, Blasey C, Sigmon S, Beebe KL. Buprenorphine implants for treatment of opioid dependence: randomized comparison to placebo and sublingual buprenorphine/naloxone. Addiction. 2013 Dec;108(12):2141-9. doi: 10.1111/add.12315. Epub 2013 Sep 18.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: April 27, 2010
• First Submitted That Met QC Criteria: April 30, 2010
• First Posted (Estimate): May 3, 2010

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-806; 1RC2DA028910-01 (U.S. NIH Grant/Contract)