Evaluation of Buprenorphine Extended-Release Subcutaneous Injection at Alternative Injection Locations

Study Overview
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Brief Summary
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Extended-release buprenorphine (SUBLOCADE®) injection is currently approved for subcutaneous administration in 4 different quadrants of the abdomen for treatment of opioid use disorder (OUD). Injection locations are rotated to minimize irritation. Having 1 or more alternate injection sites is desirable for patients who may be taking SUBLOCADE for extended durations, based upon clinical response. The primary objective of this study is to assess the relative bioavailability of extended-release buprenorphine when administered at alternative injection locations (test treatments), in comparison to the abdomen (reference treatment).

Official Title
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A Single-Dose Study to Evaluate the Relative Bioavailability, Safety, and Tolerability of SUBLOCADE at Alternative Injection Locations in Adults

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: Buprenorphine Extended-Release Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed the informed consent form (ICF) and have the ability to comply with the requirements and restrictions listed therein. Sex: male or female. Between the ages of 18 and 65 years inclusive, at the time of signing the ICF. Currently meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for moderate or severe opioid use disorder (OUD), or documented history of moderate to severe OUD and receiving/stabilized on medicine for opioid use disorder (MOUD). Body mass index: ≥ 18.0 to ≤ 33.0 kg/m^2. New to treatment and seeking MOUD, or currently prescribed transmucosal (TM) buprenorphine (BUP) for OUD at the dose of 12 mg daily or can dose adjust to 12 mg daily. Agree not to take any BUP-containing products, other than those administered for the current study, throughout the duration of the study. Exclusion Criteria: Has current diagnosis, other than OUD, requiring chronic opioid treatment. Has concurrent primary substance use disorder, as defined by DSM-5 criteria, other than opioid, tobacco, cannabis, or mild to moderate alcohol use disorders. Has target areas unsuitable for subcutaneous injections or evaluation of injections site (eg, nodules, scarring, lesions, excessive pigment) in the areas designated for possible injection in the study. Has had significant traumatic injury or major surgical procedure (as defined by the investigator) within 30 days prior to the first dose of SUBLOCADE or still recovering from prior such injury or surgery. Known personal and/or family history of congenital QT prolongation, or taking Class IA antiarrhythmic medications (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (eg, sotalol, amiodarone) or other medications that prolong the QT interval. Known family history of sudden unexplained death. Currently taking (within the 30 days prior to signing the ICF) prescription or over-the-counter medications that are clinically relevant CYP 3A4 or CYP 2C8 inducers or inhibitors (eg, rifampin, azole antifungals [eg, ketoconazole], macrolide antibiotics [eg, erythromycin]). Has history of suicidal ideation within 30 days prior to informed consent or history of a suicide attempt in the 6 months prior to informed consent. Has any active medical condition, or psychiatric illness, or social/legal situation (including court order requiring treatment for OUD), or organ disease, or concurrent medication/treatment that may compromise participant safety, interfere with study endpoints, or limit compliance with study requirements, or compromise the ability of the participant to provide written informed consent. Moderate or severe hepatic impairment (Child-Pugh B or C). Has known allergy or hypersensitivity to BUP or any component of the ATRIGEL Delivery System. Concurrent or has had prior treatment with any BUP long-acting injectable product (eg, SUBLOCADE) in the past 3 years prior to consent; or treatment with depot naltrexone within the 3 months prior to consent. Treatment with another investigational agent within 30 days prior to Screening or enrollment in another clinical study (except for an observational study). Concurrent treatment with medications contraindicated for use with BUP as per local prescribing information. Is a member of site staff, has a financial interest in Indivior, or is an immediate family member of anyone directly involved in the study (ie, site staff or Indivior employee).

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Extended-release Buprenorphine: Abdomen<br>Participants will receive a single, subcutaneous injection of 300 mg extended-release buprenorphine in the abdomen on Day 1. | Drug: Buprenorphine Extended-Release Injection<br>* Administered as a subcutaneous injection.<br>* Other names: SUBLOCADE®;|
| Experimental: Extended-release Buprenorphine: Upper Arm<br>Participants will receive a single, subcutaneous injection of 300 mg extended-release buprenorphine in the back of the upper arm on Day 1. | Drug: Buprenorphine Extended-Release Injection<br>* Administered as a subcutaneous injection.<br>* Other names: SUBLOCADE®;|
| Experimental: Extended-release Buprenorphine: Buttocks<br>Participants will receive a single, subcutaneous injection of 300 mg extended-release buprenorphine in the buttocks on Day 1. | Drug: Buprenorphine Extended-Release Injection<br>* Administered as a subcutaneous injection.<br>* Other names: SUBLOCADE®;|
| Experimental: Extended-release Buprenorphine: Thigh<br>Participants will receive a single, subcutaneous injection of 300 mg extended-release buprenorphine in the thigh on Day 1. | Drug: Buprenorphine Extended-Release Injection<br>* Administered as a subcutaneous injection.<br>* Other names: SUBLOCADE®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve from Study Day 1 to Day 29 (AUC0-28days) of Buprenorphine |  | Day 1 at predose and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 hours post-dose and on Days 4, 6, 8, 11, 15, 18, 22, 25, and 29 | 
| Maximum Observed Plasma Concentration (Cmax) of Buprenorphine |  | Day 1 at predose and at 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48 hours post-dose and on Days 4, 6, 8, 11, 15, 18, 22, 25, and 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with Treatment-emergent Adverse Events |  | 28 days | 
| Number of Participants with Treatment-emergent Adverse Events Identified as Injection Site Reactions |  | 28 days | 
| Number of Participants with Treatment-emergent Serious Adverse Events |  | 28 days | 
| Injection Site Grading | Injection sites will be assessed for pain, tenderness, erythema/redness, induration, or swelling. Local injection site tolerability will be assigned a severity grade, including none (grade 0), mild (grade 1), moderate (grade 2), severe (grade 3), or potentially life-threatening (grade 4) utilizing the Injection Site Grading Scale. | Day 1 at 10 minutes and 2 hours post dosing | 
| Injection Site Pain | Measured on a 100 mm visual analog scale (VAS), where 0 represents no pain and 100 represents maximum pain. | Day 1 at 1, 5, 10, 15, and 30 minutes post dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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medicine for opioid use disorder (MOUD)