INDV-6001 Multiple-Dose Pharmacokinetic Study

The current study will evaluate the pharmacokinetics, safety, and tolerability of INDV-6001 following multiple doses in participants with opioid use disorder in order to select optimum dosing regimens for future studies. Prior to receiving INDV-6001, participants will be stabilised on 12-16 mg of transmucosal BUP (SUBOXONE®) or will transition from a monthly maintenance dose of subcutaneous extended-release BUP (SUBLOCADE®). This study will also evaluate the use of alternative injection sites (thigh, back of upper arm), which may be desirable in this patient population for the anticipated extended durations of treatment.

There are 6 cohorts testing varying dose strengths and frequencies of INDV-6001.

* Cohorts 1-4 are suitable for participants that are not receiving long-acting treatment for OUD.
* Cohorts 5-6 are suitable for participants currently receiving SUBLOCADE.

There are 3 periods within this study.

* Screening Period: from the screening visit until prior to the first SUBOXONE or SUBLOCADE dose as a part of this study.
* Pre-Investigational Medicinal Product (IMP) Period: from the first SUBOXONE or SUBLOCADE dose as a part of this study until prior to the first INDV-6001 dose.
* IMP Period: from the first INDV-6001 dose until the end of the study.

Eligibility Criteria:
Inclusion Criteria:

Participants are eligible to be included in any cohort open to enrolment in the study only if all of the following criteria apply:

1. Signed the informed consent form (ICF) and have the ability to understand and comply with the requirements and restrictions listed therein.
2. Adults (male or female) between the ages of 18 and 65 years, inclusive, at the time of signing the ICF.
3. Body mass index ≥18.0 to ≤33.0 kg/m2.
4. Seeking medication for opioid use disorder (MOUD), and:

   1. Cohorts 1-4: Currently meets or has documented history of moderate or severe opioid use disorder (OUD) as per DSM-5 criteria; can be dose adjusted to 12-16 mg SUBOXONE once a day (QD) or currently taking transmucosal buprenorphine (TM BUP) for OUD and can be dose adjusted to 12 to 16 mg SUBOXONE QD;
   2. Cohort 5: Currently prescribed and compliant (in the opinion of the investigator) with SUBLOCADE at the maintenance dose of 100 mg (2 initial doses of 300 mg SUBLOCADE followed by a minimum of one 100 mg dose of SUBLOCADE) with injection intervals of approximately every 4 weeks;
   3. Cohort 6: Currently prescribed and compliant (in the opinion of the investigator) with SUBLOCADE at the maintenance dose of 300 mg (a minimum of 5 consecutive 300 mg doses of SUBLOCADE) with injection intervals of approximately every 4 weeks.
5. Agree not to take any buprenorphine (BUP)-containing products, other than those administered for the current study, throughout the duration of the study.
6. Women participants of childbearing potential agree to follow contraception guidelines per study protocol. Women of non-childbearing potential are women who are:

   1. Postmenopausal (defined as no menses for 12 months without an alternative medical cause and confirmed by high follicle-stimulating hormone (FSH) level of \>30 mIU/mL in women not using hormonal contraception or hormonal replacement therapy)
   2. Permanently sterilized (e.g. bilateral tubal occlusion, bilateral tubal ligation, complete hysterectomy, bilateral salpingectomy, bilateral oophorectomy)
7. Male participants agree to follow contraception guidelines per study protocol.

Exclusion Criteria:

A participant will not be eligible for inclusion in this study if any of the following criteria apply:

1. Has current diagnosis or medical condition, other than OUD, requiring chronic opioid treatment.
2. Has concurrent primary substance use disorder, as defined by DSM-5 criteria, other than opioid, tobacco, cannabis, or mild to moderate alcohol use disorders.
3. Has injection area unsuitable for subcutaneous (SC) injections (eg, nodules, scarring, lesions, excessive pigment) in the areas designated for possible injection in the study.
4. Currently using another MOUD treatment other than TM BUP (eg, SUBOXONE) or SUBLOCADE, or has had prior treatment with any long-acting injectable form of a BUP-containing product in the past 2 years prior to consent (except for Cohorts 5-6); treatment with oral naltrexone or methadone products within 14 days prior to consent; or treatment with depot naltrexone within the 3 months prior to consent.
5. Has had significant traumatic injury or major surgical procedure (as defined by the Investigator) within 30 days prior to the first dose of INDV-6001 or still recovering from such prior injury or surgery.
6. Has congenital long QT syndrome, history of prolonged QT in the 3 months prior to screening, or a corrected QT interval (Fridericia's - QTcF) \>450 msec (male) or \>470 msec (female), or history of risk factors for Torsades de Pointes. Has known personal history of taking Class IA antiarrhythmic medications (eg, quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (eg, sotalol, amiodarone) or other mediations that prolong the QT interval.
7. Has known family history of congenital QT prolongation or sudden unexplained death.
8. Currently taking (within the 30 days prior to signing the ICF) prescription or over the counter (OTC) medications that are clinically relevant cytochrome P450 (CYP) 3A4 or CYP 2C8 inducers or inhibitors (eg, rifampin, azole antifungals \[eg, ketoconazole\], macrolide antibiotics \[eg, erythromycin\]).
9. History of suicidal ideation within 30 days prior to providing written informed consent (evidenced by answering yes to either question 1 or 2 on the Columbia-Suicide Severity Rating Scale \[C-SSRS\]) or history of a suicide attempt in the 6 months prior to consent.
10. Has any active medical condition (including organ disease), psychiatric illness, social/legal situation (including court order requiring treatment for OUD), or concurrent medication/treatment that may compromise participant safety, interfere with study endpoints, limit compliance with study requirements, or compromise the ability of the participant to provide written informed consent.
11. Has active hepatitis B or C as evidenced by positive serology and polymerase chain reaction (PCR) test confirmation.
12. Has total bilirubin ≥1.5 × ULN (with direct bilirubin \>1.3 mg/dL), ALT ≥3 × ULN, AST ≥3 × ULN, or INR \>1.5 × ULN at Screening).
13. Has serum creatinine \>1.5 × ULN or estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73m2 by CKD-EPI formula.
14. Has known allergy or hypersensitivity to BUP, any excipients of INDV-6001, SUBOXONE, or SUBLOCADE.
15. Currently participating in another interventional clinical study, and/or has been treated with investigational product INDV-2000 within 1 month prior to Screening Visit, or another investigational agent within 3 months prior to Screening Visit.
16. Currently treated with medications contraindicated for use with BUP as per local prescribing information.
17. Has donated more than 500 mL of blood within the past 3 months prior to consent.
18. Is a member of site staff, has a financial interest in Indivior, or is an immediate family member of anyone directly involved in the study (eg, site staff or Indivior employee).