INDV-6001 Multiple-Dose Pharmacokinetic Study

Phase 2Active Not RecruitingNCT06576843

Indivior Inc.123 enrolled

Overview

This is a multicentre, open-label, multiple dose study of INDV-6001 in adult participants with moderate or severe OUD as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). The current study will evaluate the pharmacokinetics (PK), safety, and tolerability of INDV-6001 following multiple doses in participants with OUD to select optimum dosing regimens for future studies. Prior to receiving INDV-6001, participants will be stabilised on 12-16 mg of transmucosal (TM) BUP (SUBOXONE®) or will transition from a 100-mg monthly maintenance dose of SC 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.

Study Cohorts: There are multiple cohorts (1, 2, 3, 4 and 7) testing varying dose strengths and frequencies of INDV-6001 in participants who are not receiving long-acting treatment for OUD. Up to 15 participants from each of the Cohorts 1, 2, 3, and 4 will enrol into Cohorts 1a, 2a, 3a, and 4a, respectively. Study Periods: 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 SUBLOCADE injection (Cohorts 3a and 4a only) or until the end of the study (EOS; all remaining cohorts) Post-IMP Period: (Cohorts 3a and 4a only) from the SUBLOCADE injection until EOS

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

123

Interventions

INDV-6001DRUG

Extended-release subcutaneous injection

SuboxoneDRUG

Oral sublingual film

SublocadeDRUG

Extended-release subcutaneous injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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. Has signed the ICF and have the ability to understand and comply with the requirements and restrictions listed therein 2. Is an adult (male or female) between the ages of 18 and 65 years, inclusive, at the time of signing the ICF 3. Has a BMI of ≥18.0 to ≤33.0 kg/m2 4. Is seeking MOUD and currently meets or has documented history of moderate or severe OUD as per DSM-5 criteria. For Cohorts 1-4 only: can be dose-adjusted to 12 to 16 mg SUBOXONE QD or currently taking TM BUP for OUD and can be dose-adjusted to 12 to 16 mg SUBOXONE QD 5. Agrees not to take any BUP-containing products, other than those administered for the current study, throughout the duration of the study 6. If a woman of childbearing potential, not pregnant or lactating and agrees to follow contraception guidelines per protocol; if a women of non-childbearing potential (WONCBP), is: 1. Postmenopausal (defined as no menses for 12 months without an alternative medical cause and confirmed by high FSH level of \>30 mIU/mL in women not using hormonal contraception or hormonal replacement therapy) or 2. Permanently sterilised (eg, bilateral tubal occlusion, bilateral tubal ligation, complete hysterectomy, bilateral salpingectomy, bilateral oophorectomy) 7. If a man, agrees to follow contraception guidelines per protocol 5.2 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 a 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 an injection area unsuitable for SC injections (eg, nodules, scarring, lesions, excessive pigment) in the areas designated for possible injection in the study 4. Is currently using another MOUD treatment other than TM BUP (eg, SUBOXONE) or has had prior treatment with any long-acting injectable form of a BUP-containing product in the past 18 months (or if 18-24 months with a positive UDS) prior to consent; treatment with oral naltrexone or methadone products within 14 days prior to consent (or positive UDS for methadone at Screening); 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. Is currently taking (within the 30 days prior to signing the ICF) prescription or OTC medications that are clinically relevant moderate or strong cytochrome P450 (CYP) 3A4 or CYP 2C8 inducers or inhibitors (eg, rifampin, azole antifungals \[eg, ketoconazole\], macrolide antibiotics \[eg, erythromycin\]) 9. Has a 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 C-SSRS) or a 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 PCR test confirmation 12. Has total bilirubin ≥1.5 × ULN (with direct bilirubin \>20% of total bilirubin), 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. Is 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. Is currently being 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)

Locations (11)

Artemis Institute for Clinical Research

San Diego, California, United States

Innovative Clinical Research, Inc.

Miami Lakes, Florida, United States

Chicago Clinical Research Institute Inc.

Chicago, Illinois, United States

Precise Research Centers

Flowood, Mississippi, United States

Hassman Research Institute (Cenexel HRI - Marlton)

Marlton, New Jersey, United States

Richmond Behavioral Associates

Staten Island, New York, United States

Midwest Clinical Research

Dayton, Ohio, United States

Insite Clinical Research, LLC

DeSoto, Texas, United States

Memorial Hermann Village

Houston, Texas, United States

Pillar Clinical Research

Richardson, Texas, United States

...and 1 more locations

Outcomes

Primary Outcomes

Steady-state area under the plasma concentration-time curve over the dosing interval (AUCtau) of buprenorphine following INDV-6001 injection in the abdomen

AUCtau for Cohorts 1-4

Time frame: Up to 260 days

Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 injection in the abdomen

Cmax for Cohorts 1-4

Time frame: Up to 260 days

Steady-state time to attain the maximum observed plasma concentration (Tmax) of buprenorphine following INDV-6001 injection in the abdomen

Tmax for Cohorts 1-4

Time frame: Up to 260 days

Steady-state minimum plasma concentration over a dosing interval (Cmin) of buprenorphine following INDV-6001 injection in the abdomen

Cmin for Cohorts 1-4

Time frame: Up to 260 days

Steady-state plasma concentration measured at the end of the dosing interval (Ctrough) of buprenorphine following INDV-6001 injection in the abdomen

Ctrough for Cohorts 1-4

Time frame: Up to 260 days

Steady-state average plasma concentration over the dosing interval (Cavg) of buprenorphine following INDV-6001 injection in the abdomen

Cavg for Cohorts 1-4

Time frame: Up to 260 days

Steady-state ratio of peak to trough plasma concentrations over a dosing interval (% fluctuation) of buprenorphine following INDV-6001 injection

% fluctuation for Cohorts 1-4

Time frame: Up to 260 days

Steady-state area under the plasma concentration-time curve over the dosing interval (AUCtau) of buprenorphine following INDV-6001 injection in the back of the upper arm Vs abdomen injection location

AUCtau for Cohort 1a \[Day 260 injection in the back of the upper arm\] Vs Cohort 1 \[Day 176 Injection in the abdomen\]

Time frame: Up to 168 days [24 weeks]

Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 injection in the back of the upper arm Vs abdomen injection location

Cmax for Cohort 1a \[Day 260 injection in the back of the upper arm\] Vs Cohort 1 \[Day 176 Injection in the abdomen\]

Time frame: Up to 168 days [24 weeks]

Steady-state time to attain the maximum observed plasma concentration (Tmax) of buprenorphine following INDV-6001 injection in the back of the upper arm Vs abdomen injection location

Tmax for Cohort 1a \[Day 260 injection in the back of the upper arm\] Vs Cohort 1 \[Day 176 Injection in the abdomen\]

Time frame: Up to 168 days [24 weeks]

Steady-state minimum plasma concentration over a dosing interval (Cmin) of buprenorphine following INDV-6001 injection in the back of the upper arm Vs abdomen injection location

Cmin for Cohort 1a \[Day 260 injection in the back of the upper arm\] Vs Cohort 1 \[Day 176 Injection in the abdomen\]

Time frame: Up to 168 days [24 weeks]

Steady-state plasma concentration measured at the end of the dosing interval (Ctrough) of buprenorphine following INDV-6001 injection in the back of the upper arm Vs abdomen injection location

Ctrough for Cohort 1a \[Day 260 injection in the back of the upper arm\] Vs Cohort 1 \[Day 176 Injection in the abdomen\]

Time frame: Up to 168 days [24 weeks]

Steady-state average plasma concentration over the dosing interval (Cavg) of buprenorphine following INDV-6001 injection in the back of the upper arm Vs abdomen injection location

Cavg for Cohort 1a \[Day 260 injection in the back of the upper arm\] Vs Cohort 1 \[Day 176 Injection in the abdomen\]

Time frame: Up to 168 days [24 weeks]

Steady-state ratio of peak to trough plasma concentrations over a dosing interval (% fluctuation) of buprenorphine following INDV-6001 injection in the back of the upper arm Vs abdomen injection location

% fluctuation for Cohort 1a \[Day 260 injection in the back of the upper arm\] Vs Cohort 1 \[Day 176 Injection in the abdomen\]

Time frame: Up to 168 days [24 weeks]

Steady-state area under the plasma concentration-time curve over the dosing interval (AUCtau) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location

AUCtau for Cohort 2a \[Day 232 injection in the Thigh\] Vs Cohort 2 \[Day 176 injection in the abdomen\]

Time frame: Up to 128 days [16 weeks]

Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location

Cmax for Cohort 2a \[Day 232 injection in the Thigh\] Vs Cohort 2 \[Day 176 injection in the abdomen\]

Time frame: Up to 128 days [16 weeks]

Steady-state time to attain the maximum observed plasma concentration (Tmax) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location

Tmax for Cohort 2a \[Day 232 injection in the Thigh\] Vs Cohort 2 \[Day 176 injection in the abdomen\]

Time frame: Up to 128 days [16 weeks]

Steady-state minimum plasma concentration over a dosing interval (Cmin) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location

Cmin for Cohort 2a \[Day 232 injection in the Thigh\] Vs Cohort 2 \[Day 176 injection in the abdomen\]

Time frame: Up to 128 days [16 weeks]

Steady-state plasma concentration measured at the end of the dosing interval (Ctrough) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location

Ctrough for Cohort 2a \[Day 232 injection in the Thigh\] Vs Cohort 2 \[Day 176 injection in the abdomen\]

Time frame: Up to 128 days [16 weeks]

Steady-state average plasma concentration over the dosing interval (Cavg) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location

Cavg for Cohort 2a \[Day 232 injection in the Thigh\] Vs Cohort 2 \[Day 176 injection in the abdomen\]

Time frame: Up to 128 days [16 weeks]

Steady-state ratio of peak to trough plasma concentrations over a dosing interval (% fluctuation) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location

% fluctuation for Cohort 2a \[Day 232 injection in the Thigh\] Vs Cohort 2 \[Day 176 injection in the abdomen\]

Time frame: Up to 128 days [16 weeks]

Secondary Outcomes

Assessment of the safety and tolerability of INDV-6001 injection

Incidence, severity, and relatedness of treatment-emergent adverse events (TEAEs), serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, and AEs of special interest (AESIs) for All Cohorts

Time frame: Up to 260 days

Steady-state area under the plasma concentration-time curve over the dosing interval (AUCtau) of buprenorphine following INDV-6001 250mg injection in the abdomen Vs SUBLOCADE 300mg injection in the abdomen

AUCtau for Cohort 3 \[Day 99 250mg INDV-6001 injection in the abdomen\] Vs Cohort 3a \[Day 127 300mg SUBLOCADE injection in the abdomen\]