Side effects of medication

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.

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.

Inclusion Criteria:

• Study participants must:

  1. Be 18 to 65 years of age, inclusive;
  2. Able to understand and speak English or Spanish
  3. Be interested in reducing or stopping MA use;
  4. Meet Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria for moderate or severe MUD (4 or more criteria);
  5. Self-report MA use on 18 or more days in the 30-day period prior to written consent using the TLFB;
  6. 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;
  7. 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;
  8. 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;
  9. 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.
  10. 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;
  11. Be willing and able to provide consent and comply with all study procedures and medication instructions.

Exclusion Criteria:

• Study participants must not:

  1. Have suicidal or homicidal ideation that requires immediate attention;
  2. 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;
  3. 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;
  4. Have been in a study of pharmacological or behavioral treatment for addiction within 6 months prior to written study consent (smoking cessation excepted);
  5. Have taken an investigational drug in another study within 30 days prior to written study consent;
  6. Have been prescribed and taken buprenorphine or methadone within 30 days prior to written study consent;
  7. Be concurrently enrolled in formal behavioral or pharmacological addiction treatment services at the time of written consent;
  8. 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;
  9. 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;
  10. 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;
  11. 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;
  12. If biologically female, be currently pregnant, breastfeeding, or planning on conception;
  13. Hypersensitivity (e.g., anaphylaxis) to buprenorphine or any component of the ATRIGEL formulation or their excipients;
  14. Have an abdominal area unsuitable for subcutaneous injections by the judgment of the Medical Clinician;
  15. Have other medical, psychiatric or other factors that in the judgment of the Medical Clinician could make participation difficult or unsafe.

Data from this study will be available to researchers on the website https://datashare.nida.nih.gov/ after the study is complete and the data is analyzed. This website will not include information that can identify individual study participants. The following information will be posted: Study protocol, reference to study publication of primary outcome, data sets (SAS and ASCII ), annotated case report forms, define file (also known as Data Dictionary), study-specific de-identification notes. Prior to downloading any study data, the user will be prompted to complete a registration agreement for data use. Users will have to register a name and valid e-mail address in order to download data and to accept their responsibility for using data in accordance with the National Institute on Drug Abuse (NIDA) Data Share Agreement.

After the study is complete and the data is analyzed

Study-specific de-identification notes will be posted on the website (URL provided here)

Baseline characteristics collected for all the18 enrolled & randomized participants are reported here. 2 subjects withdrew consent prior to starting sublingual buprenorphine (SL-BUP) induction procedure and only the participants who successfully completed the open-label SL-BUP induction procedures started the study medication [injectable formulation (experimental/placebo)] that is reflected in Participant Flow module and that number is different from analysis population reported in this module.

Adverse event assessment will initiate with participant written informed consent to 30 days post last study visit (approximately 19 weeks).

All Adverse events that occurred during the sublingual buprenorphine (SL-BUP) induction period for all randomized subjects as well as the subjects who continued to study medication period (injectable formulation-experimental/ placebo) are reported here. Hence, the number of participants at risk is greater than the number started study medication in Participant flow module.

Only the Data and Statistic Center (DSC) staff overseeing the random assignment schedule, a few Clinical Coordinating Center (CCC) staff, the central research pharmacy staff preparing the study medication and a single study staff role (Medical Personnel) to administer the injections are unblinded; all other study personnel and participants will remain blinded to treatment arm until the nationwide completion of the trial and the database is formally locked.