Re-Treatment Study of Probuphine in Opioid Addiction

A Phase 3, Six-Month, Open-Label, Re-Treatment Study of Probuphine in Opioid Addiction

Probuphine (buprenorphine implant) is an investigational implant placed just below the skin containing buprenorphine (BPN). BPN is an approved treatment for opioid dependence. This is a 6-month, open-label, re-treatment study that will confirm the safety and efficacy of Probuphine in patients who have previously completed the 6-month PRO-806 study with either Probuphine, placebo or sublingual buprenorphine.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 85
• 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
    • 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
      • Stanley Street Treatment and Resources, Inc
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Psych Care Consultants Research
  • New York
    • New York, New York, United States, 10025
      • St. Luke's Roosevelt Hospital Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center
  • 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: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has voluntarily provided written informed consent prior to conducting any study-related procedures
• Completion of 24 weeks of treatment in PRO-806
• Subject has been deemed appropriate for entry into this extension study by the investigator
• Females of childbearing potential must be willing to use a reliable means of contraception during the entire study.

Exclusion Criteria:

• An aspartate aminotransferase (AST) levels ≥ 3 X the upper limit of normal, alanine aminotransferase (ALT) levels ≥ 3 X the upper limit of normal, total bilirubin ≥ 1.5 X the upper limit of normal, or creatinine ≥ 1.5 X upper limit of normal on the screening laboratory assessments
• A current diagnosis of chronic pain requiring opioids for treatment
• A pregnant or lactating female
• 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)
• A history of coagulopathy within the past 90 days, and/or current anti-coagulant therapy such as warfarin
• A 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
• Any 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probuphine; patients are first inducted on sublingual buprenorphine then switched to 4 Probuphine Implants	Drug: Probuphine (buprenorphine implant); Implantable formulation of buprenorphine made of buprenorphine HCl/ethylene vinyl acetate, considered a drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with Adverse Events (AEs) as a measure of safety	AEs that occurred after the signing of the informed consent until 4 weeks after the implants have been removed were followed. Serious AEs and AEs that were designated as possibly related to study drug were followed until resolution or stabilization.	29 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetic analyses through plasma buprenorphine concentration in subjects as a measure of efficacy	24 weeks
Percent of subjects retained as a measure of efficacy	24 weeks
Percent of subjects reporting illicit drug use as a measure of efficacy	24 weeks
Average daily dose of supplemental sublingual buprenorphine as a measure of efficacy	24 weeks
Mean total score on SOWS as a measure of efficacy	24 weeks
Mean total score on COWS as a measure of efficacy	24 weeks
Mean subjective opioid cravings scores as a measure of efficacy	24 weeks
Mean total score on Beck Depression Inventory (BDI-II) as a measure of efficacy	24 weeks
Patient-rated opioid use and problems Responder Analysis as a measure of efficacy	24 weeks
Physician-rated severity of opioid use and symptoms Responder Analysis as a measure of efficacy	24 weeks
Overall satisfaction with treatment reported on Patient Satisfaction Survey	24 weeks

Collaborators and Investigators

• Sponsor: Titan Pharmaceuticals
• Investigators: Principal Investigator: Katherine L. Beebe, Ph.D., 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.
• White J, Bell J, Saunders JB, Williamson P, Makowska M, Farquharson A, Beebe KL. Open-label dose-finding trial of buprenorphine implants (Probuphine) for treatment of heroin dependence. Drug Alcohol Depend. 2009 Jul 1;103(1-2):37-43. doi: 10.1016/j.drugalcdep.2009.03.008. Epub 2009 Apr 28.

Helpful Links

• Related Info

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 16, 2010
• First Posted (Estimate): December 17, 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; Compulsive Behavior; Impulsive Behavior; Opioid-Related Disorders; Behavior, Addictive; 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-811