Clinical Trial of CAM2038, Long-acting Subcutaneous Buprenorphine Injections for Treatment of Patients With Opioid Dependence

A Phase III, Randomized, Double-Blind, Active-Controlled, Parallel Group, Multi-center Trial Assessing the Efficacy and Safety of a Once-Weekly and Once-Monthly, Long-Acting Subcutaneous Injectable Depot of Buprenorphine (CAM2038) in Treatment of Adult Outpatients With Opioid Use Disorder

Phase III, randomized, double-blind, double-dummy, active-controlled, parallel group multi-center trial, designed to evaluate the non-inferiority of CAM2038 compared to an existing standard of care (SL BPN/NX) in initiation and maintenance treatment with BPN.

Study Overview

• Status: Completed
• Conditions: Opioid Use Disorders
• Intervention / Treatment: Drug: SL BPN/NX tabs; Drug: placebo SC injections; Drug: CAM2038 SC injection; Drug: SL placebo tablets

Detailed Description

This is a Phase III, randomized, double-blind, double-dummy, active-controlled, parallel group multi-center trial, designed to evaluate the non-inferiority of CAM2038 compared to an existing standard of care (SL BPN/NX) in initiation and maintenance treatment with BPN. The trial will involve 4 phases: Screening, Phase 1 (weekly visits), Phase 2 (monthly visits), and Follow-up.

Approximately 380 subjects (190 subjects per arm) will be randomized.

• Study Type: Interventional
• Enrollment (Actual): 428
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35215
      • Parkway Medical Center
    • Haleyville, Alabama, United States, 35565
      • Haleyville Clinical Research LLC
    • Hamilton, Alabama, United States, 35570
      • Boyett Health Services Inc
  • California
    • Lemon Grove, California, United States, 91945
      • Synergy East
    • Oceanside, California, United States, 92056
      • North County Clinical Research
    • Panorama City, California, United States, 91402
      • Asclepes Research
    • San Diego, California, United States, 92103
      • Artemis Institute for Clinical Research
    • San Francisco, California, United States, 94708
      • Care Practice
    • West Hollywood, California, United States, 90046
      • Synergist Research
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Dr Vijapura and Associates
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research Inc
    • Maitland, Florida, United States, 32751
      • Try Research
    • Miami, Florida, United States, 33173
      • Tellus Clinical Research, Inc.
    • North Miami, Florida, United States, 33161
      • Scientific Clinical Research, Inc.
  • Kansas
    • Wichita, Kansas, United States, 67203
      • Professional Research Network of Kansas, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40508
      • University of Kentucky Medical Center
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Stanley Street Treatment and Resources Inc
    • New Bedford, Massachusetts, United States, 02740
      • Novex Clinical Research
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research Centers
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • PsychCare Consultants Research
    • Saint Louis, Missouri, United States, 63141
      • St. Louis Clinical Trials
  • New Jersey
    • Belvidere, New Jersey, United States, 07823
      • Wellness and Research Center
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
  • New York
    • New York, New York, United States, 10019
      • STARS/Columbia University
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuro-Behavioral Clinical Research Center
    • Dayton, Ohio, United States, 45417
      • Midwest Clinical Research Center
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Rivus Wellness & Research Institute
  • Pennsylvania
    • Conshohocken, Pennsylvania, United States, 19428
      • Frost Medical Group
    • Philadelphia, Pennsylvania, United States, 19104
      • The University of Pennsylvania Health System Treatment Research Center
  • Rhode Island
    • Lincoln, Rhode Island, United States, 02865
      • Lincoln Research
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Carolina Clinical Trials, Inc
  • Texas
    • Dallas, Texas, United States, 75115
      • InSite Clinical Research
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Washington
    • Seattle, Washington, United States, 98107
      • Swedish Health Services

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:

1. Subject must provide written informed consent prior to the conduct of any trial-related procedures.
2. Male or female, 18-65 years of age, inclusive.
3. Diagnosis of moderate or severe opioid use disorder as described (DSM-V).
4. Voluntarily seeking treatment for opioid use disorder.
5. Have not received medication-assisted treatment for opioid use disorder within 60 days prior to randomization.
6. Considered by the Investigator to be a good candidate for BPN treatment, based on medical and psychosocial history.
7. Male or Female subjects of childbearing potential must be willing to use a reliable method of contraception during the entire trial (Screening visit to Follow-up visit)

Exclusion Criteria:

1. Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS).
2. Current diagnosis of chronic pain requiring opioids for treatment.
3. Current DSM-V diagnosis of moderate to severe substance use disorder on any other psychoactive substances other than opioids, caffeine or nicotine (e.g., alcohol, cocaine, sedatives).
4. Pregnant or lactating or planning to become pregnant during the trial.
5. Hypersensitivity or allergy to BPN or other opioids, naloxone or other opioid antagonists, or excipients of CAM2038 or SL BPN.
6. Requires current use of agents that are strong inhibitors or inducers of cytochrome P450 3A4 (CYP3A4) such as some azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., clarithromycin), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir).
7. Subjects with active signs or symptoms of hepatitis and requiring treatment. Subjects with no acute signs of inflammation, and no clinical necessity for therapy will be allowed, at the discretion of the Investigator.
8. Recent history of or current evidence of suicidal ideation or active suicidal behavior as based on the Columbia Suicide Severity Rating Scale (C-SSRS) ("Yes" responses to questions 4 or 5).
9. Any pending legal action that could prohibit participation or compliance in the trial.
10. Exposure to any investigational drug within the 4 weeks prior to Screening.
11. Participants with a history of risk factors of Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) or an electrocardiogram (ECG) demonstrating a Fridericia's corrected QT interval (QTcF) >450 msec in males and QTcF >470 in females at screening.
12. 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, or other clinically significant laboratory abnormalities, which in the opinion of the Investigator may prevent the subject from safely participating in trial.
13. Significant symptoms, medical conditions, or other circumstances which, in the opinion of the Investigator, would preclude compliance with the protocol, adequate cooperation in the trial or obtaining informed consent, or may prevent the subject from safely participating in trial (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for CAM2038).
14. Is an employee of the Investigator or the trial site, with direct involvement in the proposed trial or other trials under the direction of the Investigator or trial site, or is a family member of an employee or of the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SL BPN/NX tabs + placebo SC injections; SL BPN/NX: 2 mg/0.5 mg or 8 mg/2 mg BPN/naloxone tablets administered daily, at doses of 8 mg/2 mg to 32 mg/8 mg per day. CAM2038 placebo: 0.16, 0.32, 0.48 and 0.64 mL SC injection administered once weekly or once monthly (matching volumes for CAM2038 q1w and near-matching volumes for CAM2038 q4w).	Drug: SL BPN/NX tabs; Other Names: Suboxone; Drug: placebo SC injections; Other Names: placebo
Experimental: CAM2038 SC injections + SL placebo tabs; CAM2038 q1w: BPN FluidCrystal® SC injection depot for once weekly administration (50 mg/mL) at doses of 8, 16, 24 or 32 mg (BPN base) (0.16, 0.32, 0.48 or 0.64 mL SC injection). CAM2038 q4w: BPN FluidCrystal® SC injection depot for once monthly administration (356 mg/mL) at doses of 64, 96, 128 or 160 mg (BPN base) (0.18, 0.27, 0.36 or 0.45 mL SC injection). SL placebo: tablets matching 2 mg/0.5 mg and 8 mg/2 mg SL BPN doses, administered daily	Drug: CAM2038 SC injection; Other Names: Buprenorphine injection; Drug: SL placebo tablets; Other Names: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate, Denoted by Response Rate (Weeks 1-24).	Response Rate, denoted by response rate (Weeks 1-24). A responder is defined as a subject with at least 33% of urine toxicology results collected during the Phase 1 (4 out of 12 urine samples) and 67% of urine toxicology results collected during Phase 2 (4 out of 6 urine samples) being negative for illicit opioids and self - reported illicit opioid use.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Distribution Function (CDF) of Percentage of Urine Samples Negative for Illicit Opioids	Cumulative distribution function (CDF) of percentage of urine samples negative for illicit opioids comparing CAM2038 to SL BPN/NX as (supported by self-reported opioid use results)	24 weeks
Number of Subjects With Sustained Abstinence of Opioid Use	Number of Subjects with Sustained Abstinence of Opioid Use taking SL BPN/NX and CAM2038	24 weeks
Number of Subjects Remaining in the Study (Retention Rate)	Number of Subjects Remaining in the Study (Retention Rate) on SL BPN/NX and CAM2038	24 weeks

Collaborators and Investigators

• Sponsor: Braeburn Pharmaceuticals
• Investigators: Study Chair: Braeburn Pharmaceuticals, Braeburn Pharmaceuticals

Publications and helpful links

General Publications

• Lofwall MR, Walsh SL, Nunes EV, Bailey GL, Sigmon SC, Kampman KM, Frost M, Tiberg F, Linden M, Sheldon B, Oosman S, Peterson S, Chen M, Kim S. Weekly and Monthly Subcutaneous Buprenorphine Depot Formulations vs Daily Sublingual Buprenorphine With Naloxone for Treatment of Opioid Use Disorder: A Randomized Clinical Trial. JAMA Intern Med. 2018 Jun 1;178(6):764-773. doi: 10.1001/jamainternmed.2018.1052.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: December 30, 2015
• First Submitted That Met QC Criteria: January 7, 2016
• First Posted (Estimate): January 11, 2016

Study Record Updates

• Last Update Posted (Actual): August 22, 2019
• Last Update Submitted That Met QC Criteria: August 6, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• 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: HS-11-421

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No