Clinical trial NCT01114308: A Six-Month Randomized Controlled Trial (RCT) of Probuphine Safety and Efficacy in Opioid Addiction
Official title: A Randomized, Placebo and Active-Controlled, Multi-Center Study of Probuphine in Patients With Opioid Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opioid Dependency
Keywords: opioid dependence
opioid addiction
buprenorphine
implant
methadone
heroin
suboxone
opioid pain medication
opioid withdrawal
Lead sponsor: Titan Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2010-05-03
Enrollment: 287
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: CDF of the percent of urine samples negative for opioids in Probuphine and Placebo groups from weeks 1-24
timeFrame: 1-24 weeks
measure: 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
timeFrame: 1-24 weeks
Secondary outcomes:
measure: CDF of the percent of urine samples negative for opioids from weeks 1-16
timeFrame: 1-16 weeks
measure: CDF of the percent of urine samples negative for opioids from weeks 17-24
timeFrame: 17-24 weeks
measure: Difference of proportion of urine samples negative for illicit opioids over 24 weeks of treatment for Probuphine vs. SL BPN
timeFrame: 24 weeks
Other outcomes:
measure: Percent urines negative for illicit opioids
timeFrame: 24 weeks
measure: Percent of study completers
timeFrame: 24 weeks
measure: Mean total score on the SOWS
timeFrame: 24 weeks
measure: Mean total score on the COWS
timeFrame: 24 weeks
measure: Mean subjective opioid craving assessment using Visual Analog Scale (VAS)
timeFrame: 24 weeks
measure: Patient-rated Clinical Global Improvement (CGI)
timeFrame: 24 weeks
measure: Physician-rated Clinical Global Improvement (CGI)
timeFrame: 24 weeks
measure: Mean total number of weeks of abstinence
timeFrame: 24 weeks
measure: Mean maximum period of continuous abstinence
timeFrame: 24 weeks
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: National City
country: United States
facility: Synergy Clinical Research Center
state: California
city: Oceanside
country: United States
facility: North County Clinical Research
state: California
city: Torrance
country: United States
facility: Friends Research Institute
state: California
city: Jacksonville
country: United States
facility: Amit Vijapura, MD
state: Florida
city: Largo
country: United States
facility: Operation PAR, Inc. - TC Campus
state: Florida
city: Lauderhill
country: United States
facility: Fidelity Clinical Research, Inc.
state: Florida
city: North Miami
country: United States
facility: Scientific Clinical Research, Inc.
state: Florida
city: Baltimore
country: United States
facility: BPRU, Behavioral Biology Research Center
state: Maryland
city: Fall River
country: United States
facility: SSTAR: Stanley Street Treatment and Resources, Inc.
state: Massachusetts
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Saint Louis
country: United States
facility: PsychCare Consultants Research
state: Missouri
city: New York
country: United States
facility: New York VA Medical Center, NYU School of Medicine
state: New York
city: New York
country: United States
facility: St. Luke's Roosevelt Hospital Center
state: New York
city: Durham
country: United States
facility: Duke University, Duke Addictions Program
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Carolina Clinical Trials, Inc.
state: South Carolina
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Everett
country: United States
facility: Providence Behavioral Health Services
state: Washington
Study officials:
affiliation: Titan Pharmaceuticals
name: Katherine L. Beebe, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.