Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1. Are outpatients 18 to 75 years of age, inclusive, at the time of signing the informed
consent.
Type of participant and disease characteristics
2. Have a current mild, moderate or severe OUD diagnosis per DSM-5 criteria at screening
as per SCID-5-CT.
3. Are intermittently using opioids such as, but not limited to, prescription opioids, heroin,
or fentanyl, defined by having used opioids 4 to 20 days in the past 28 days and at least 1
use in the past 10 days prior to V1 per TLFB.
4. Provides at least 1 opioid positive UDS (other than buprenorphine) collected either
 during screening (V1 or V2) at study site, or
 within the past 30 days prior to screening (V1) by buprenorphine provider, with
verbal or written confirmation provided to study staff.
Notes:
 During screening, 1 retest of UDS is permitted.
 UDS tests should be taken at least 5 days apart from each other.
 Verbal reports, including date of collection, received from buprenorphine
provider must be documented in writing by study staff.
5. At the time of screening are taking transmucosal (sublingual or buccal) BUP±NX
(generally optimized at 16-32 mg/day sublingual or equivalent) for 8 to 52 weeks for the
treatment of OUD. Refer to Section 10.10 for confirmation of buprenorphine dose.
Notes:
 The buprenorphine treatment episode is defined from the date of buprenorphine
initiation to the day of screening. If the participant had previous buprenorphine
treatment, the current treatment episode begins on the day of buprenorphine
initiation after the last 30-day period the participant did not use buprenorphine.
 Participant may be included if on 8-15 mg and an attempt to increase dose to
16 mg was made, but dose was de-escalated due to intolerability.
 TLFB at screening shows daily adherence to the current dose, with no more than
1 day missed per week and no more than 3 days missed per month.
6. At the time of screening, agrees to remain on buprenorphine within a dose range of 8-32
mg for the duration of the study.
7. Tests positive for buprenorphine on local UDS during screening (V1 and V2) and before
randomization (V3).
Note: During screening, 1 retest of UDS is permitted.
8. Participant is confirmed to meet study criteria and is an appropriate candidate for the
research study by the prescriber of the BUP±NX if the investigator is not the prescriber
for the BUP±NX.
Note: Verbal reports received from buprenorphine provider must be documented in
writing by study staff.
Weight
9. Have a BMI ≥22.0 kg/m2 at screening (V1) and at randomization (V3).
10. Have had a stable body weight for the 90 days prior to randomization (V3) defined as less
than 5% body weight reduction.
Sex assigned at birth and contraceptive/barrier requirements
11. Are individuals AMAB or AFAB, including both IOCBP and INOCBP.
Contraceptive use by participants should be consistent with local regulations regarding
the methods of contraception for those participating in clinical studies. For the
reproduction definitions and contraception requirements of this protocol, refer to
Section 10.4.
Study procedures
12. 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.

Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
OUD related
14. Between screening (V1) and randomization (V3), have initiated OUD-specific treatment
or therapy (behavioral or other non-drug, e.g. acupuncture or hypnosis) or are planning to
initiate such therapy during the trial.
Exceptions: Narcotics Anonymous and other 12 step programs, brief medication
counseling, general supportive psychotherapy and/or self-help group are permitted.
Substance-abuse related
15. Have evidence of current or within the past 180 days prior to screening (V1), history of
any substance use disorder(s) of any severity, as defined by the DSM-5, with a pattern of
persistent illicit or non-prescribed substance use as indicated by clinical interview, except
 any level of opioid and tobacco use disorder
 mild-to-moderate alcohol or cannabis use disorder
Note: any level of caffeine use is allowed.
16. Not motivated to refrain from all use of drug(s) of abuse, except for alcohol, nicotine, and
cannabis, during the study.
17. Unable to provide at least one negative UDS for drugs of abuse (other than opioid or
cannabis) at screening (V1 and V2) and/or randomization (V3).
Note: If UDS is positive for drugs of abuse (other than opioid or cannabis) participant
must provide evidence of prescription to be permitted as concomitant use or provide a
negative result on a subsequent screening visit.
18. Have more than 7 days of inpatient treatment for substance abuse
 within 30 days before screening (V1), or
 between screening (V1) and randomization (V3).
19. Had opioid overdose in past 6 months prior to screening (V1), by self-report or as
reported by the buprenorphine provider

**Additional criteria apply