Extension to Safety and Efficacy of Probuphine in the Treatment of Opioid Dependence (PRO-807)

An Open-Label, Multi-Center Extension 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 (buprenorphine implant) 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 patient with opioid dependence. Patients who have completed 24 weeks of treatment in the Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of Probuphine in Patients with Opioid Dependence, will be re-treated with Probuphine over an additional 24 weeks.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States
      • David Geffen School of Medicine at UCLA
    • National City, California, United States, 91950
      • Synergy Clinical Research Center
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Amit Vijapura, MD
    • Lauderhill, Florida, United States
      • Fidelity Clinical Research, Inc.
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc.
  • Maryland
    • Baltimore, Maryland, United States
      • Behavioral Biology Research Unit, Johns Hopkins Bayview Campus
  • Massachusetts
    • Fall River, Massachusetts, United States
      • Dual Diagnosis Unit, SSTAR: Stanley Street Treatment and Resources, Inc.
  • Michigan
    • Detroit, Michigan, United States
      • Wayne State Univ. School of Medicine, Dept of Psychiatry & Behavioral Neuroscience
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Psych Care Consultants Research
  • New York
    • New York, New York, United States
      • New York VA Medical Center, NYU School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke 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, 98201-1067
      • Providence Behavioral Health Services
    • Seattle, Washington, United States
      • Puget Sound Health CareSystem

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 conduct of any study-related procedures
• Completed 24 weeks of treatment in PRO-805
• Deemed appropriate for entry into this extension study by the Investigator
• Females of childbearing potential and fertile males must use a reliable means of contraception

Exclusion Criteria:

• 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
• Current diagnosis of chronic pain requiring opioids for treatment
• Pregnant or lactating females
• Current use of agents metabolized through cytochrome P450 3A4 (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
• Current use of benzodiazepines other than physician prescribed use
• Significant medical or psychiatric symptoms, cognitive impairment, or other factors which in the opinion of the Investigator, 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Probuphine; buprenorphine implant	Drug: Probuphine (buprenorphine implant); Implantable formulation of buprenorphine made of buprenorphine HCl/ethylene vinyl acetate, considered a drug. (4 implants, 6-month duration).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with adverse events as a measure of safety	Adverse events that occurred after the signing of the informed consent until 14 days after study drug treatment has been discontinued, or AEs designated as possibly-related to study drug and all Serious AEs until resolution or stabilization, were followed.	approx. 26 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Physician-rated severity of opioid use and symptoms Responder Analysis as a measure of efficacy	24 weeks
Buprenorphine concentration in plasma	24 weeks
Percent of urine samples that are negative for illicit opioids	24 weeks
Mean composite score Drug Problems area of Addiction Severity Index	Baseline and End of Treatment
Patient-rated Opioid use and Problems Responder Analysis as a measure of efficacy	24 weeks

Collaborators and Investigators

• Sponsor: Titan Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (ACTUAL): February 1, 2009
• Study Completion (ACTUAL): February 1, 2009

Study Registration Dates

• First Submitted: February 26, 2008
• First Submitted That Met QC Criteria: March 5, 2008
• First Posted (ESTIMATE): March 6, 2008

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-807