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

Titan Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Opioid Dependency

Treatments: Drug: Buprenorphine; Drug: Probuphine (buprenorphine implant); Drug: placebo implant

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT01114308

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

PRO-806

Details and patient eligibility

About

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.

Enrollment: 287 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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287 participants in 3 patient groups, including a placebo group

Probuphine

Experimental group

Description:

Patients are first inducted on SL BPN then switched to 4 buprenorphine implants

Treatment:

Drug: Probuphine (buprenorphine implant)

placebo implant

Placebo Comparator group

Description:

patients are first inducted on SL BPN then switched to 4 placebo implants

Treatment:

Drug: placebo implant

sublingual buprenorphine

Active Comparator group

Description:

patients are inducted on SL BPN, then continue on SL BPN

Treatment:

Drug: Buprenorphine