Pharmacokinetics, Safety, and Tolerability of Depot Buprenorphine at Three Different Molecular Weights in Treatment-Seeking Subjects With Opioid Use Disorder

Study Overview
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Brief Summary
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This is a single-center, randomized, open-label, single-dose, parallel-group study which will enroll and randomize approximately 48 subjects (to achieve 36 completers) with opioid use disorder (OUD) who are seeking treatment for OUD. The study includes both a Residential (Inpatient) and Non-Residential (Outpatient) Period.

Official Title
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A Single-Center, Randomized, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Depot Buprenorphine (RBP-6000) Using Poly (DL-lactide-co-glycolide) Polymer of Two Different Molecular Weights (Low and High Molecular Weights as Test Treatments) in Comparison to Intermediate Molecular Weight (Reference Treatment) in Treatment-Seeking Subjects With Opioid Use Disorder

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: RBP-6000
* Drug: SUBOXONE Sublingual Film


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently meets DSM-5 criteria for moderate or severe opioid use disorder (OUD) Is seeking treatment for OUD Body mass index: ≥ 18.0 to ≤ 35.0 kg/m^2 Females: Female individuals of childbearing potential (defined as all women who are not surgically sterile or postmenopausal for at least 1 year prior to informed consent) must have a negative serum pregnancy test prior to enrollment and must agree to use a medically acceptable means of contraception from Screening through at least 6 months after the last dose of Investigational Medicinal Product (IMP). Males: Male individuals with female partners of child-bearing potential must agree to use medically acceptable contraception after signing the informed consent form through at least 6 months after the last dose of IMP. Male individuals must also agree not to donate sperm during the study and for 6 months after receiving the last dose of IMP. Have a normal electrocardiogram (ECG) or ECG with no clinically significant findings in the opinion of the Investigator or medically qualified sub-investigator at Screening and through pre-dose on Day 1. Agree not to take any buprenorphine-containing products, other than those administered for the current study, throughout the duration of the study. Willing to adhere to study procedures and provide written informed consent prior to start of any study procedures. Exclusion Criteria: Current diagnosis, other than OUD, requiring chronic opioid treatment. Pregnant or lactating females. Have an ECG demonstrating a corrected QT interval using Fridericia's calculation (QTcF) > 450 msec in males and QTcF > 470 msec in females upon admission to the residential facility or prior to administration of RBP-6000. Currently meet the criteria for diagnosis of moderate or severe substance use disorder, by DSM-5 criteria, for any substances other than opioids, and/or tobacco. Had a significant traumatic injury, major surgery, or open biopsy within the 4 weeks prior to signing the informed consent form. Used buprenorphine-containing products within the 14 days prior to signing the informed consent form. Have a history of suicidal ideation within the 30 days prior to signing the informed consent form or prior to study drug administration Have a history or presence of allergic or adverse response (including rash or anaphylaxis) to buprenorphine, naloxone, methadone, or the ATRIGEL Delivery System. Individuals who have a positive urine drug screen (UDS) prior to admission to the residential facility for barbiturates, benzodiazepines, buprenorphine, or methadone.

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 |
| --- | --- |
| Experimental: RBP-6000 - Light MW<br>Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with a light molecular weight (MW) polymer. | Drug: RBP-6000<br>* RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine.<br>* Other names: buprenorphine;Drug: SUBOXONE Sublingual Film<br>* Subjects will be dose-stabilized on SUBOXONE sublingual film prior to administration of RBP-6000. SUBOXONE sublingual film will be administered beginning after the subject is experiencing signs and symptoms of withdrawal on Day -8 and continue until Day -1.<br>* Other names: buprenorphine HCl and naloxone HCl dihydrate;|
| Experimental: RBP-6000 - Heavy MW<br>Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with a heavy molecular weight (MW) polymer. | Drug: RBP-6000<br>* RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine.<br>* Other names: buprenorphine;Drug: SUBOXONE Sublingual Film<br>* Subjects will be dose-stabilized on SUBOXONE sublingual film prior to administration of RBP-6000. SUBOXONE sublingual film will be administered beginning after the subject is experiencing signs and symptoms of withdrawal on Day -8 and continue until Day -1.<br>* Other names: buprenorphine HCl and naloxone HCl dihydrate;|
| Active Comparator: RBP-6000 - Intermediate MW<br>Single subcutaneous injection of RBP-6000 (buprenorphine) 300 mg, formulated with an intermediate molecular weight (MW) polymer (reference). | Drug: RBP-6000<br>* RBP-6000 uses buprenorphine in the ATRIGEL Delivery System. The single-syringe is prefilled with RBP-6000 containing 300 mg buprenorphine.<br>* Other names: buprenorphine;Drug: SUBOXONE Sublingual Film<br>* Subjects will be dose-stabilized on SUBOXONE sublingual film prior to administration of RBP-6000. SUBOXONE sublingual film will be administered beginning after the subject is experiencing signs and symptoms of withdrawal on Day -8 and continue until Day -1.<br>* Other names: buprenorphine HCl and naloxone HCl dihydrate;|

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 | Relative bioavailability will be assessed using AUC0-28days. | Day 1 to Day 29 | 
| Maximum Observed Plasma Concentration (Cmax) of Buprenorphine | Relative bioavailability will also be assessed using Cmax | Day 1 to Day 57 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-Time Curve from Study Day 1 to Day 29 (AUC0-28days) of Norbuprenorphine |  | Day 1 to Day 29 | 
| Maximum Observed Plasma Concentration (Cmax) of Norbuprenorphine |  | Day 1 to Day 57 | 
| Participants with Treatment-Emergent Adverse Events |  | Day 1 to Day 57 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Buprenorphine, opioid use disorder