The purpose of this study is to see if brenipatide, when compared to placebo, is safe and effective for participants with opioid use disorder, when used with buprenorphine with or without naloxone.

The maximum potential duration of study participation for a participant in Part A is approximately 144 weeks, maximum potential duration of study participation for a participant in Part B is approximately 116 weeks. The actual duration will vary for each participant depending on the time of enrollment and the overall rate of study enrollment.

The study consists of 2 parts, each with its own participant cohort

• Part A: double-blind treatment with open-label extension (OLE)
• Part B: open-label treatment.

Participants will be enrolled in only one part of the study.

Inclusion Criteria:

• Have a current mild, moderate or severe opioid use disorder (OUD)

• Are reliable and willing to make themselves available for the duration of the study (for example, are not incarcerated, not homeless) and attend required study visits, and are willing and able to follow study procedures as required, such as

  • self-inject study intervention Note: Participants who are not able to perform the injections must have the assistance of a support person trained to administer the study intervention
  • store and use the provided study intervention as directed
  • maintain electronic or paper study diaries, as applicable, and
  • complete the required questionnaires

• Are intermittently using non-legal, non-prescribed opioids

• Are taking buprenorphine for treatment on OUD

Exclusion Criteria:

• Evidence of other substance use disorder(s) within 180 days of screening, except the following are permitted: any level tobacco use disorder, mild-to-moderate alcohol or mild-to-moderate cannabis use disorder

Note: any level of caffeine use is allowed

• Are actively suicidal or deemed a significant risk for suicide

• Have a history of advanced liver disease (including advanced liver fibrosis or cirrhosis or alcohol-associated hepatitis based on either prior liver histology or imaging studies, such as transient elastography, ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI), or Enhanced Liver Fibrosis score

• Have participated in a clinical study and received active treatment, or unknown if they received active treatment, within 90 days or 5 half-lives (whichever is longer) before screening

• Had opioid overdose in past 6 months prior to screening

• Have a lifetime history or current diagnosis of the following:

  • schizophrenia or other psychotic disorder
  • bipolar disorder
  • borderline personality disorder
  • any eating disorder

• Have type 1 diabetes mellitus, or a history of ketoacidosis, or hyperosmolar state, or coma

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication or approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal should be approved by an independent review panel and researchers should sign a data sharing agreement.