Long-Term Safety Study of Buprenorphine (CAM2038) in Adult Outpatients With Opioid Use Disorder

Study Overview
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Brief Summary
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Open-label multi-center, 48 week safety study, consistent with standard practice for long-term safety studies. This one year safety study will utilize CAM2038 q1w (once weekly) and q4w (once monthly) and will have 3 phases: Screening, Treatment, and Follow-up.

Detailed Description
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Open-label multi-center, 48 week safety study, consistent with standard practice for long-term safety studies. This one year safety study will utilize CAM2038 q1w (once weekly) and q4w (once monthly) and will have 3 phases: Screening, Treatment, and Follow-up. Patients who are currently taking sublingual (SL) BPN (weekly or monthly prescription visits) or individuals who are actively seeking BPN treatment but who have not yet begun a treatment regimen, may be eligible for the study. Following Screening, qualified subjects meeting inclusion criteria and not meeting exclusion criteria will be initiated on either CAM2038 q1w or q4w, based on their current treatment status (qualified subjects currently on SL BPN or seeking BPN treatment). Qualified subjects will be initiated or transitioned to CAM2038 q1w or q4w as follows: Initiation of BPN treatment - initiate with CAM2038 q1w Currently receiving SL BPN treatments - transfer to corresponding CAM2038 q1w or q4w dose

Official Title
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An Open-Label Multicenter Study Assessing the Long-Term Safety of a Once-Weekly and Once-Monthly, Long-Acting Subcutaneous Injection Depot of Buprenorphine (CAM2038) in Adult Outpatients With Opioid Use Disorder

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: CAM2038 q1w or q4w exposure to SL BPN/NX
* Drug: CAM2038 q1w or q4w new to BPN treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must provide written informed consent prior to the conduct of any study-related procedures. Male or female, 18-65 years of age, inclusive. Female subjects of childbearing potential must be willing to use a highly effective method of contraception during the entire study (Screening Visit to Follow-Up Visit). Current diagnosis of moderate or severe opioid use disorder (DSM-V) or past medical history of opioid use disorder currently being treated with SL BPN. Considered by the Investigator to be a good candidate for BPN treatment, based on medical and psychosocial history. Subjects must meet one of the following criteria for BPN treatment history: Voluntarily seeking treatment for opioid use disorder (not currently on BPN treatment for at least last 60 days but seeking BPN treatment), or; Currently on SL BPN treatment. Exclusion Criteria: Current diagnosis of Acquired Immune Deficiency Syndrome (AIDS). Current diagnosis of chronic pain requiring opioids for treatment. Current DSM-V diagnosis for moderate to severe substance use disorder (including alcohol) other than opioids, caffeine or nicotine and currently being treated as the primary substance use disorder. 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). Pregnant or lactating or planning to become pregnant during the study. Hypersensitivity or allergy to naloxone (only for subjects receiving the SL BPX test dose), BPN or excipients of CAM2038. Requires chronic use of agents that are strong inhibitors or inducers of cytochrome P450 3A4 (CYP 3A4) such as some azole antifungals (e.g., ketoconazole), macrolide antibiotics (e.g., clarithromycin), or protease inhibitors (e.g., ritonavir, indinavir, and saquinavir). Hepatitis, unless under stable treatment, at the discretion of the Investigator. Any pending legal action that could prohibit participation or compliance in the study. Exposure to any investigational drug within the 4 weeks prior to Screening. 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 study. Participants with a history of risk factors of Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) or an ECG demonstrating a Fridericia's corrected QT interval (QTcF) >450 msec in males and QTcF > 470 in females at screening. Significant symptoms, medical conditions, or other circumstances which, in the opinion of the Investigator, would preclude compliance with the protocol, adequate cooperation in the study or obtaining informed consent, or may prevent the subject from safely participating in study. This includes, but is not limited to, subjects with attention deficit hyperactivity disorder receiving central stimulants (e.g. methylphenidate or other central stimulants), as well as subjects with severe respiratory insufficiency, respiratory depression, airway obstruction, gastrointestinal motility disorders, severe hepatic insufficiency, planned surgery and prior treatment with monoamine oxidase inhibitors. Is an employee of the Investigator or the trial site, with direct involvement in the proposed trial or other studies under the direction of the Investigator or trial site, or is a family member of an employee or of the Investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAM2038 q1w or q4w exposure to SL BPN/NX<br>CAM2038 (buprenorphine FluidCrystal®) Subjects previously exposed to SL BPN/NX who received CAM2038 q1w or q4w | Drug: CAM2038 q1w or q4w exposure to SL BPN/NX<br> <br> * Other names: Buprenorphine injection;|
| Experimental: CAM2038 q1w or q4w new to BPN treatment<br>CAM2038 (buprenorphine FluidCrystal®) New to BPN Treatment who received CAM2038r q1w or q4w | Drug: CAM2038 q1w or q4w new to BPN treatment<br> <br> * Other names: Buprenorphine injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Overall Safety Population | Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period. Safety Assessments: Adverse events (AEs) and serious adverse events (SAEs)-Overall Safety Population | 12 months- 48 week | 
| Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period-Full Exposure Safety Population | Subjects With Treatment-Emergent Adverse Events (TEAE) During the Treatment Period. Safety Assessments: Adverse events (AEs) and serious adverse events (SAEs)-Full Exposure Safety Population | 12 months- 48 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage of Negative Urine Toxicology Results for Illicit Opioid Use Supported by Self Reported Illicit Opioid Use (Efficacy Population) | The following is a summary of Mean Percentage of Negative Urine Toxicology Results for Illicit Opioid Use Supported by Self Reported Illicit Opioid Use (Efficacy Population) | 12 months (48 weeks) | 
| Mean Percentage of Self-reported No Illicit Opioid Use (Efficacy Population) | The following is a summary of Mean Percentage of Self-Reported No Illicit Opioid Use during the entire study (Efficacy Population). The proportion of patients who reported no illicit opioid use during the study was analyzed. For example if a subject provided 10 self reports and 2 out of the 10 were Used, the percentage for the subject would be 20%. The average percentage of all patients is provided. | 12 months (48 weeks) | 
| Summary of Retention in Treatment (Efficacy Population) | The following is a summary of treatment retention over 48 weeks | 48 weeks of treatment | 
| Summary of Clinical Opiate Withdrawal Scale (COWS) at Selected Time Points (Efficacy Population) | A summary of COWS (administered by the Clinician) over 48 weeks to show withdrawal symptoms from baseline to end of treatment. This scale consists of 11 common opiate withdrawal signs or symptoms, rated on a numeric scale from 0 to 4 or 5 and based on a timed period of observation of the subject by the rater. Higher scores are associated with greater withdrawal symptoms with a total range for all items of between 0-48 | 12 months- 48 week | 
| Summary of Subjective Opiate Withdrawal Scale (SOWS) at Selected Time Points (Efficacy Population) | Summary of SOWS over time to show withdrawal symtons, from baseline to end of treatment. This form contains 16 questions that rate the intensity of withdrawal from 0 (Not at all) to 4 (Extremely), with higher scores associated with greater withdrawal symptoms and total range for all items of 0-64 | 12 months- 48 week | 
| Summary of Desire to Use Visual Analog Scale (VAS) at Selected Time Points (Efficacy Population) | The following table summarizes the desire to use measurements over a period of 12 months - 48 weeks. Desire to Use assessments were administered using a unipolar 100 mm VAS. Subjects were asked Since your last scheduled assessment visit, indicate your worst or strongest desire to use opioids, where 0 = No desire to use and 100 mm = Strongest possible desire. | 12 months- 48 week | 
| Summary of Need to Use Visual Analog Scale (VAS) at Selected Time Points (Efficacy Population) | The following results summarize the need to use VAS over a period of 12 months - 48 weeks. Need to Use assessments were administered using a unipolar 100 mm VAS. Subjects were asked Since your last scheduled assessment visit, indicate your worst or strongest need to use opioids, where 0 = No need to use and 100 mm = Strongest possible need. | 12 months- 48 week |