Opioid Use Disorders
Conditions
Brief summary
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.
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.
Interventions
DRUGCAM2038 SC injection
DRUGSL BPN/NX tabs
DRUGplacebo SC injections
DRUGSL placebo tablets
Sponsors
Braeburn Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate, Denoted by Response Rate (Weeks 1-24). | 24 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Distribution Function (CDF) of Percentage of Urine Samples Negative for Illicit Opioids | 24 weeks | 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) |
| Number of Subjects With Sustained Abstinence of Opioid Use | 24 weeks | Number of Subjects with Sustained Abstinence of Opioid Use taking SL BPN/NX and CAM2038 |
| Number of Subjects Remaining in the Study (Retention Rate) | 24 weeks | Number of Subjects Remaining in the Study (Retention Rate) on SL BPN/NX and CAM2038 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: SL BP/NX Tablets + 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). | 215 |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets CAM2038 q1w: BPN FluidCrystal® SC injection depot for once weekly administration (50 mg/mL) at doses of 8, 16, 24 and 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 | 213 |
| Total | 428 |
Baseline characteristics
| Characteristic | Group 1: SL BP/NX Tablets + Placebo SC Injections | Group 2: CAM2038 SC Injections + SL Placebo Tablets | Total |
|---|---|---|---|
| Age, Continuous | 38.0 years STANDARD_DEVIATION 10.89 | 38.7 years STANDARD_DEVIATION 11.17 | 38.4 years STANDARD_DEVIATION 11.02 |
| BMI | 26.2 kg/m^2 STANDARD_DEVIATION 5.55 | 25.6 kg/m^2 STANDARD_DEVIATION 5.03 | 25.9 kg/m^2 STANDARD_DEVIATION 5.3 |
| Race/Ethnicity, Customized Race/Ethnicity Hispanic or Latino | 24 Participants | 25 Participants | 49 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Not Hispanic or Latino | 191 Participants | 188 Participants | 379 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 48 Participants | 47 Participants | 95 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 164 Participants | 159 Participants | 323 Participants |
| Sex: Female, Male Female | 73 Participants | 92 Participants | 165 Participants |
| Sex: Female, Male Male | 142 Participants | 121 Participants | 263 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 215 | 1 / 213 |
| other Total, other adverse events | 119 / 215 | 128 / 213 |
| serious Total, serious adverse events | 16 / 215 | 5 / 213 |
Outcome results
Primary
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.
Time frame: 24 weeks
Population: Includes all subjects who were randomized and receiving at least one dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: SL BP/NX Tablets + Placebo SC Injections | Response Rate, Denoted by Response Rate (Weeks 1-24). | Responder | 31 Participants |
| Group 1: SL BP/NX Tablets + Placebo SC Injections | Response Rate, Denoted by Response Rate (Weeks 1-24). | Non-Responder | 184 Participants |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets | Response Rate, Denoted by Response Rate (Weeks 1-24). | Responder | 37 Participants |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets | Response Rate, Denoted by Response Rate (Weeks 1-24). | Non-Responder | 176 Participants |
p-value: <0.001Chi-squared
Secondary
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)
Time frame: 24 weeks
Population: Includes all subjects who were randomized and receiving at least one dose of study drug.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Group 1: SL BP/NX Tablets + Placebo SC Injections | Cumulative Distribution Function (CDF) of Percentage of Urine Samples Negative for Illicit Opioids | With Subjects' Self Reported Opioid Use | 0.0 percentage of negative urine samples |
| Group 1: SL BP/NX Tablets + Placebo SC Injections | Cumulative Distribution Function (CDF) of Percentage of Urine Samples Negative for Illicit Opioids | Without Subjects' Self reported Opioid Use | 6.7 percentage of negative urine samples |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets | Cumulative Distribution Function (CDF) of Percentage of Urine Samples Negative for Illicit Opioids | With Subjects' Self Reported Opioid Use | 26.7 percentage of negative urine samples |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets | Cumulative Distribution Function (CDF) of Percentage of Urine Samples Negative for Illicit Opioids | Without Subjects' Self reported Opioid Use | 26.7 percentage of negative urine samples |
Comparison: including subject self-reported opioid usep-value: 0.004Wilcoxon Rank-Sum
Comparison: not including self-reported opioid usep-value: 0.008Wilcoxon Rank-Sum
Secondary
Number of Subjects Remaining in the Study (Retention Rate)
Number of Subjects Remaining in the Study (Retention Rate) on SL BPN/NX and CAM2038
Time frame: 24 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: SL BP/NX Tablets + Placebo SC Injections | Number of Subjects Remaining in the Study (Retention Rate) | Retained | 126 Participants |
| Group 1: SL BP/NX Tablets + Placebo SC Injections | Number of Subjects Remaining in the Study (Retention Rate) | Not Retained | 89 Participants |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets | Number of Subjects Remaining in the Study (Retention Rate) | Retained | 121 Participants |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets | Number of Subjects Remaining in the Study (Retention Rate) | Not Retained | 92 Participants |
p-value: 0.006Chi-squared
Secondary
Number of Subjects With Sustained Abstinence of Opioid Use
Number of Subjects with Sustained Abstinence of Opioid Use taking SL BPN/NX and CAM2038
Time frame: 24 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: SL BP/NX Tablets + Placebo SC Injections | Number of Subjects With Sustained Abstinence of Opioid Use | Subjects with sustained abstinence of opioids | 30 Participants |
| Group 1: SL BP/NX Tablets + Placebo SC Injections | Number of Subjects With Sustained Abstinence of Opioid Use | Subjects without sustained abstinence of opioids | 185 Participants |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets | Number of Subjects With Sustained Abstinence of Opioid Use | Subjects with sustained abstinence of opioids | 39 Participants |
| Group 2: CAM2038 SC Injections + SL Placebo Tablets | Number of Subjects With Sustained Abstinence of Opioid Use | Subjects without sustained abstinence of opioids | 174 Participants |