A Study of Adult Outpatients With Opioid Dependence Transitioned From a Daily SL Buprenorphine to Probuphine® Subdermal Implants

NCT02180659 | Completed Phase 3 Results

• 1 other identifier: PRO-814
• Study Type: interventional
• Target: 177
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of the study is to demonstrate maintenance of treatment efficacy when transferring adult outpatients with opioid dependence, who are clinically stabilized on 8 mg or less of sublingual (SL) buprenorphine (BPN), to 4 Probuphine implants compared to SL BPN. The secondary objective of the study is to confirm safety of 4 Probuphine implants in adult outpatients with opioid dependence who are clinically stabilized on 8 mg or less of SL BPN.

Conditions

Opioid Dependence

Outcome Measures

Primary Outcomes (1)

• The Primary Efficacy Endpoint is a Responder Rate Analysis, Where a Responder is Defined as a Patient With no More Than 2 of 6 Months With Any Evidence of Illicit Opioid Use.

  The primary efficacy endpoint is a responder analysis. A subject will be designated as a responder (meaning they have maintained stability) if they have no more than 2 of 6 months with any evidence of illicit opioid use. Evidence of illicit opioid use is defined as a positive opioid urine toxicology result or self-reported illicit opioid use.

  24 weeks

Secondary Outcomes (7)

• Percent of Subjects With no Urine Illicit Opioid Use by Month;

  24 weeks

• Number of Participants With Evidence of Urine Illicit Opioid Use by Month

  24 weeks

• Percent of Subjects With no Self-reported Illicit Drug Use by Month

  24 weeks

• Measures of Craving: Desire to Use Visual Analogue Scale (VAS)

  24 weeks

• Measures of Withdrawal: Clinical Opiate Withdrawal Scale (COWS)

  24 weeks

Study Arms (2)

buprenorphine implants + placebo tablets

EXPERIMENTAL

Four 80 mg Probuphine implants + daily SL placebo tablets

Drug: Buprenorphine implant; Drug: sublingual placebo tablets

buprenorphine tablets + placebo implants

ACTIVE COMPARATOR

Daily SL BPN tablets (≤8 mg/daily) + four placebo implants

Drug: sublingual buprenorphine tablets; Drug: placebo implants

Interventions

sublingual buprenorphine tablets DRUG

buprenorphine tablets + placebo implants

Buprenorphine implant DRUG

buprenorphine implants + placebo tablets

placebo implants DRUG

buprenorphine tablets + placebo implants

sublingual placebo tablets DRUG

buprenorphine implants + placebo tablets

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must provide written informed consent prior to the conduct of any study-related procedures.
• Male or female, 18-65 years of age, inclusive.
• Primary diagnosis of opioid dependence (DSM-IV-TR).
• Subject is considered clinically stable by their treating healthcare provider and confirmed by the following:
• Subject must be on SL BPN treatment for at least 6 months.
• Subject must have been on a SL BPN dose of 8 mg or less daily for at least the last 90 days prior to Screening.
• No positive urine toxicology results for illicit opioids in the last 90 days.
• Free from significant withdrawal symptoms (score of ≤ 5 on the Clinical Opiate Withdrawal Scale \[COWS\]), as measured at the Screening Visit.
• Female subjects of childbearing potential must be willing to use a reliable method of contraception during the entire study (Screening Visit to Follow-Up Visit).

You may not qualify if:

• Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS).
• Current diagnosis of chronic pain syndrome requiring chronic opioid treatment, or conditions associated with acute episodic flares that require opioid treatment.
• Pregnant or lactating or planning to become pregnant during the study.
• Hypersensitivity or allergy to ethylene vinyl acetate (EVA)-containing substances or naloxone.
• Recent scarring or tattoos on their upper arms, or a history of keloid scarring.
• Requires current use of agents metabolized through 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.
• Current DSM-IV-TR diagnosis for substance dependence on any other psychoactive substances other than opioids or nicotine (e.g., alcohol, cocaine).
• Significant symptoms 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.
• Any pending legal action that could prohibit participation or compliance in the study.
• Exposure to any investigational drug within the 8 weeks prior to Screening.
• Aspartate aminotransferase levels ≥3 X the upper limit of normal, alanine aminotransferase 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.
• Clinically significant low platelet count on the Screening laboratory assessments, according to the Investigator.

Sponsors & Collaborators

• Titan Pharmaceuticals: lead

Related Publications (1)

• Rosenthal RN, Lofwall MR, Kim S, Chen M, Beebe KL, Vocci FJ; PRO-814 Study Group. Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine: A Randomized Clinical Trial. JAMA. 2016 Jul 19;316(3):282-90. doi: 10.1001/jama.2016.9382.

  PMID: 27434441 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Kate Beebe DeVarney
• Organization: Titan Pharmaceuticals

kdevarney@titanpharm.com

650-244-4990

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2014
• First Posted: July 3, 2014
• Study Start: July 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: May 1, 2015
• Last Updated: January 11, 2019
• Results First Posted: December 5, 2018

Record last verified: 2018-11