Monthly Injectable BUP for MA Use Disorder (MURB) Trial

Study Overview
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Brief Summary
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This study is a 12-week randomized, double-blind, placebo-controlled trial that will investigate the use of injectable buprenorphine (BUP-Inj) compared to injectable placebo (PBO-Inj) for the treatment of methamphetamine use disorder (MUD) among individuals with mild co-use of opioids.

Detailed Description
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Primary Objective: To evaluate whether assignment to 12 weeks of outpatient BUP-Inj compared to 12 weeks of outpatient PBO-Inj reduces MA use (as measured by twice-weekly urine drug screens (UDS)) during Weeks 9-12 in participants with moderate to severe MUD with co-occurring mild opioid use disorder (OUD) or opioid misuse not warranting medication for opioid use disorder (MOUD). Secondary Objectives: To evaluate whether assignment to 12 weeks of outpatient BUP-Inj compared to 12 weeks of outpatient PBO-Inj among participants with moderate to severe MUD with co-occurring mild OUD or opioid misuse not warranting MOUD improves: 1) outcomes related to alternate measures of MA use including total number of MA negative urine drug screens (UDS) during study and self-reported days of MA use; 2) measures of opioid use and self-reported frequency of opioid use; and 3) measures of MA and opioid co-use and self-reported days of MA and opioid co-use.

Official Title
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Randomized, Double-blind, Placebo-controlled Trial of Monthly Injectable Buprenorphine (BUP) for Methamphetamine (MA) Use Disorder

Conditions
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Methamphetamine-dependence

Intervention / Treatment
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* Drug: Buprenorphine injection (BUP-Inj)
* Other: Placebo injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study participants must: Be 18 to 65 years of age, inclusive; Able to understand and speak English or Spanish Be interested in reducing or stopping MA use; Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for moderate or severe MUD (4 or more criteria); Self-report MA use on 18 or more days in the 30-day period prior to written consent using the TLFB; Provide at least 2 urine samples positive for MA out of a possible 3 tests to occur at clinic visits within a 10-day period with at least 2 days between visits; Meet DSM-5 criteria for mild OUD (at least 2 but no more than 3 criteria) prior to randomization OR opioid misuse demonstrated by self-report of opioid use of at least 2 days in the 30-day period prior to written consent using the TLFB; Provide a urine drug screen negative for opioids at least once during the screening period and on the day of expected randomization to indicate control over opioid use; Have a Clinical Opiate Withdrawal Scale (COWS) score of ≤8 at both a screening visit on which they provide a UDS negative for opioids and on the day of randomization. If female, agree to use acceptable methods of contraception and have periodic urine pregnancy testing during participation in the study unless unable to get pregnant; Be willing and able to provide consent and comply with all study procedures and medication instructions. Exclusion Criteria: Study participants must not: Have suicidal or homicidal ideation that requires immediate attention; Have evidence of prolongation of the corrected QT interval (QTc) or any other finding on the screening ECG that, in the opinion of the Medical Clinician, would preclude safe participation in the study (e.g., hypokalemia, unstable atrial fibrillation) and be at significant risk for serious cardiac adverse events; Have a laboratory value with total bilirubin ≥1.5 × upper limit of normal (ULN), alanine aminotransferase (ALT) ≥3 × ULN, aspartate aminotransferase (AST) ≥5 × ULN, or serum creatinine >2 × ULN; Have been in a study of pharmacological or behavioral treatment for addiction within 6 months prior to written study consent (smoking cessation excepted); Have taken an investigational drug in another study within 30 days prior to written study consent; Have been prescribed and taken buprenorphine or methadone within 30 days prior to written study consent; Be concurrently enrolled in formal behavioral or pharmacological addiction treatment services at the time of written consent; Be receiving ongoing treatment of medications that are clinically relevant Cytochrome P450 3A4 (CYP 3A4) or Cytochrome P4502C8 (CYP 2C8) inducers or inhibitors (e.g., rifampicin, azole antifungals, macrolide antibiotics), Class IA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone) at the time of randomization that, in the judgment of the Medical Clinician, could interact adversely with study medications or put them at significant risk for development of serotonin syndrome; Have a current pattern of alcohol, benzodiazepine, or other sedative hypnotic use which would preclude safe participation in the study as determined by the Medical Clinician; Have a surgery planned or scheduled, or other treatment that would require the use of opioid-containing medications (e.g., opioid analgesics) during the study period; Currently or soon to be in jail or prison; currently in any inpatient overnight facility as required by court of law or have pending legal action or other situation that could prevent participation in the study or in any study activities; If biologically female, be currently pregnant, breastfeeding, or planning on conception; Hypersensitivity (e.g., anaphylaxis) to buprenorphine or any component of the ATRIGEL formulation or their excipients; Have an abdominal area unsuitable for subcutaneous injections by the judgment of the Medical Clinician; Have other medical, psychiatric or other factors that in the judgment of the Medical Clinician could make participation difficult or unsafe.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Injectable Buprenorphine (BUP-inj)<br>Following successful titration to 16 mg of daily sublingual buprenorphine, the participants will then transition to injectable buprenorphine (300 mg dose) every 4 weeks | Drug: Buprenorphine injection (BUP-Inj)<br>* Sublingual Buprenorphine induction, then SublocadeTM, Indivior injectable (300mg)<br>* Other names: SublocadeTM, Indivior;|
| Placebo Comparator: Injectable Placebo (PBO-inj)<br>Following successful titration to 16 mg of daily sublingual buprenorphine, the participants will then transition to injectable placebo (300 mg dose) every 4 weeks. | Other: Placebo injection<br>* Sublingual buprenorphine induction, then Placebo injectable (300 mg)<br>* Other names: Placebo injection (PBO-Inj);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of MA-negative UDS results obtained | Number of Methamphetamine (MA)-negative Urine Drug Screen (UDS) results obtained during Weeks 9 through 12 of the medication phase is measured for the BUP-Inj and PBO-Inj conditions. | week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Effective Score (TES) for MA-negative UDS results | The TES is defined to be the number of MA negative UDS divided by the number of possible UDS collected during the study. In this study there are 24 possible UDS collections so the number of MA negative UDS is divided by 24. Possible score ranges from 0-24; with higher score indicating better outcome. | week 12 | 
| Number of days of methamphetamine use during the medication phase | Number of days of methamphetamine use during treatment will be measured using Timeline Followback (TLFB) procedure which will be administered to document the participant's self-reported use during Weeks 1-12. Possible scores range from 0-84, with lower scores indicating better outcome. | week 12 | 
| Treatment Effective Score (TES) for opioid negative UDS results | The TES is defined to be the number of UDS results negative for opioids divided by the number of possible UDS collected during the study. In this study there are 24 possible UDS collections, so the number of opioid negative UDS is divided by 24. Possible score ranges from 0-24; with higher score indicating better outcome. | week 12 | 
| Number of days of opioid use during the medication phase | Number of days of opioid use during treatment will be measured using Timeline Followback (TLFB) procedure which will be administered to document the participant's self-reported opioid use at week 12. Possible scores range from 0-84, with lower scores indicating better outcome. | week 12 | 
| Treatment Effective Score (TES) for MA and opioid Co-Use compiled | The TES is defined to be the number of MA and Opioid Co-Use negative UDS divided by the number of possible UDS collected during the study. In this study there are 24 possible UDS collections, so the number of MA and Opioid Co-Use negative UDS is divided by 24. Possible score ranges from 0-24; with higher score indicating better outcome. | week 12 | 
| Number of days of MA and opioid co-use during the medication phase | Number of days of MA and opioid co-use during treatment will be measured using Timeline Followback (TLFB) procedure which will be administered to document the participant's self-reported use of substances for each day at week 12. Possible scores range from 0-84, with lower scores indicating better outcome. | week 12 |