Proof of Concept and Dose-ranging Study of INDV-2000 in Individuals With Moderate to Severe Opioid Use Disorder

Inclusion Criteria:

• Participants are eligible to be included in the study only if all of the followingcriteria apply:

1. Participant must be 18 or the legal age of consent in the jurisdiction in whichthe study is taking place to 65 years of age inclusive, at the time of signingthe informed consent.

2. Able to verbalize understanding of the consent form, able to provide writteninformed consent, and verbalize willingness to complete study procedures, beable to comply with protocol requirements, rules and regulations of study site,and be likely to complete all the study interventions.

3. Males or females with moderate or severe opioid use disorder (OUD) byDiagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)criteria who are looking to transition from daily short-term opioid agonisttreatment (medically supervised withdrawal) to non-opioid treatment.

4. Have not been on medication for opioid use for 3 months prior to the currenttreatment episode, and satisfies either a or b below.

5. The participant will initiate, or is undergoing medically supervisedwithdrawal, and

• In the opinion of the investigator, the participant is able toachieve a stable dose of transmucosal (TM) buprenorphine between ≤24mg inclusive prior to randomization.
• Current opioid agonist treatment does not exceed 35 days from thestart of TM buprenorphine to the end of Screening window.

2. The participant recently completed medically supervised withdrawal outsideof the study, and

• Time elapsed between last dose of TM buprenorphine or otherwithdrawal medication and Study Day 1/randomization does not exceed 21 calendar days.
• Recently completed opioid agonist treatment does not exceed 35 daysof TM buprenorphine dosing days inclusive of medically assistedwithdrawal dosing.

5. Male participants who are sexually active with individuals who are ofchildbearing potential must agree to use a medically acceptable forms ofcontraception from Screening until at least 90 days after the last dose ofstudy medication. The following methods of contraception are considered to bemedically acceptable: established use of oral, injected or implanted hormonalcontraception; placement of an intrauterine device or intrauterine system; oruse of a double barrier method of contraception (condom or occlusive cap withuse of a spermicide), or abstinence.

6. A female participant of non-childbearing potential, or a male of childbearingpotential if

• She agrees to use a medically acceptable form of contraception fromScreening until at least 90 days after the last dose of study medication.The following methods of contraception are considered to be medicallyacceptable: abstinence; established use or oral, injected or implantedhormonal contraception; placement of an intrauterine device orintrauterine system; or use of a double barrier method of contraception (condom or occlusive cap with use of a spermicide).
• She is not pregnant as confirmed by a negative serum screening and orurine human chorionic gonadotrophin test on Study Day 1.
• She is not lactating.

7. Body mass index (BMI) within 18.0 to 40.0 kg/m2 (inclusive)

Exclusion Criteria:

• Participants are excluded from the study if any of the following criteria apply:

1. Have a current diagnosis, other than OUD, requiring chronic opioid treatment.

2. Have a concurrent primary substance use disorder, as defined by DSM-5 criteria,other than opioid, tobacco, cannabis or alcohol use disorders.

3. Meet DSM-5 criteria for severe substance use disorder other than opioids.

4. Have a medical history of clinically significant neurological, cardiovascular,renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatricdisorder that would impact participation in the study as judged by anInvestigator or medically responsible physician.

5. Had an opioid overdose event within the 6 months prior to the Screening Visit.

6. Uses any substance of abuse via the injection route more than 2 times per weekover the last 3 months prior to Screening.

7. Have clinically significant abnormal biochemistry, hematology or urinalysisresults that would impact participation in the study as judged by anInvestigator or medically responsible physician.

8. Have a history of narcolepsy, cataplexy, obstructive or central sleep apnea.

9. Have disorders that may interfere with drug absorption, distribution,metabolism and excretion processes.

10. History of suicidal ideation within 30 days prior to providing written informedconsent as evidenced by answering "yes" to questions 4 or 5 on the suicidalideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS)completed at the Screening Visit or history of a suicide attempt (per theC-SSRS) in the 6 months prior to informed consent.

11. Serious cardiac illness or other cardiac assessments including, but not limitedto:

• Uncontrolled arrhythmias.
• History of congestive heart failure.
• Myocardial infarction <6 months from receipt of first dose ofinvestigational medicinal product (IMP)
• Uncontrolled symptomatic angina
• QT interval corrected with Fridericia's formula (QTcF) >450 msec for malesand >470 msec for females or history of prolonged QT syndrome.

12. Have any combination of the following at screening:

• Total bilirubin ≥1.5×upper limit of normal (ULN) (with direct bilirubin >1.3 mg/dL),
• Alanine aminotransferase (ALT) ≥3×ULN
• Aspartate aminotransferase (AST) ≥3×ULN
• International normalized ratio (INR) >1.2 for participants not receivinganticoagulation therapy, >3.0 for participants on conventional coagulationtherapy, >3.5 for participants on intensive anticoagulation, or
• Estimated glomerular filtration rate <60 mL/min by Cockroft-Gault formula.

13. Current symptomatic hepatic or biliary disease, including participants withcholecystectomy <90 days prior to Screening.

14. Use of a long-acting buprenorphine or naltrexone treatment for OUD within 2years or 1 year of the screening visit, respectively.

15. Concurrent treatment or treatment with an investigational drug, orparticipation in any other clinical study within 30 days prior to the signingthe informed consent form.

16. Blood or platelets donation of greater than 500 mL within 56 days or plasmadonation within 7 days of screening; clinically significant anemia or lowhemoglobin (<11 g/dL for females, <12 g/dL for males).

17. Known allergy or hypersensitivity to IMP or its excipients.

18. Any condition that, in the opinion of an Investigator or medically responsiblephysician, would interfere with evaluation of the IMP or interpretation ofparticipant safety or study results.

19. Is a member of site staff, has a financial interest in Indivior, or is animmediate family member of anyone directly involved in the study (ie, sitestaff, Indivior, or Clinical Research Organization [CRO] employee).

20. Participants who are unable, in the opinion of an Investigator or medicallyresponsible physician, to comply fully with the study requirements, includingprohibited concomitant therapies.

21. Current incarceration, treatment for OUD required by court order, or pendingincarceration/legal action that could prevent participation or compliance inthe study.