Clinical trial NCT06576843: INDV-6001 Multiple-Dose Pharmacokinetic Study
Official title: An Open-label, Multicentre Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Repeated Doses of INDV-6001 in Adults With Moderate to Severe Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Moderate to Severe Opioid Use Disorder
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2024-08-29
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

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. 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)

Primary outcomes:
measure: Steady-state area under the plasma concentration-time curve over the dosing interval (AUCtau) of buprenorphine following INDV-6001 injection in the abdomen
timeFrame: Up to 260 days
measure: Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 injection in the abdomen
timeFrame: Up to 260 days
measure: Steady-state time to attain the maximum observed plasma concentration (Tmax) of buprenorphine following INDV-6001 injection in the abdomen
timeFrame: Up to 260 days
measure: Steady-state minimum plasma concentration over a dosing interval (Cmin) of buprenorphine following INDV-6001 injection in the abdomen
timeFrame: Up to 260 days
measure: Steady-state plasma concentration measured at the end of the dosing interval (Ctrough) of buprenorphine following INDV-6001 injection in the abdomen
timeFrame: Up to 260 days
measure: Steady-state average plasma concentration over the dosing interval (Cavg) of buprenorphine following INDV-6001 injection in the abdomen
timeFrame: Up to 260 days
measure: Steady-state ratio of peak to trough plasma concentrations over a dosing interval (% fluctuation) of buprenorphine following INDV-6001 injection
timeFrame: Up to 260 days
measure: 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
timeFrame: Up to 168 days [24 weeks]
measure: Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 injection in the back of the upper arm Vs abdomen injection location
timeFrame: Up to 168 days [24 weeks]
measure: 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
timeFrame: Up to 168 days [24 weeks]
measure: 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
timeFrame: Up to 168 days [24 weeks]
measure: 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
timeFrame: Up to 168 days [24 weeks]
measure: 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
timeFrame: Up to 168 days [24 weeks]
measure: 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
timeFrame: Up to 168 days [24 weeks]
measure: 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
timeFrame: Up to 128 days [16 weeks]
measure: Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location
timeFrame: Up to 128 days [16 weeks]
measure: Steady-state time to attain the maximum observed plasma concentration (Tmax) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location
timeFrame: Up to 128 days [16 weeks]
measure: Steady-state minimum plasma concentration over a dosing interval (Cmin) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location
timeFrame: Up to 128 days [16 weeks]
measure: 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
timeFrame: Up to 128 days [16 weeks]
measure: Steady-state average plasma concentration over the dosing interval (Cavg) of buprenorphine following INDV-6001 injection in the Thigh Vs abdomen injection location
timeFrame: Up to 128 days [16 weeks]
measure: 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
timeFrame: Up to 128 days [16 weeks]
Secondary outcomes:
measure: Assessment of the safety and tolerability of INDV-6001 injection
timeFrame: Up to 260 days
measure: 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
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 250mg injection in the abdomen Vs SUBLOCADE 300mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state time to attain the maximum observed plasma concentration (Tmax) of buprenorphine following INDV-6001 250mg injection in the abdomen Vs SUBLOCADE 300mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state minimum plasma concentration over a dosing interval (Cmin) of buprenorphine following INDV-6001 250mg injection in the abdomen Vs SUBLOCADE 300mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state plasma concentration measured at the end of the dosing interval (Ctrough) of buprenorphine following INDV-6001 250mg injection in the abdomen Vs SUBLOCADE 300mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state average plasma concentration over the dosing interval (Cavg) of buprenorphine following INDV-6001 250mg injection in the abdomen Vs SUBLOCADE 300mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state ratio of peak to trough plasma concentrations over a dosing interval (% fluctuation) of buprenorphine following INDV-6001 250mg injection in the abdomen Vs SUBLOCADE 300mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state area under the plasma concentration-time curve over the dosing interval (AUCtau) of buprenorphine following INDV-6001 100mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 100mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state time to attain the maximum observed plasma concentration (Tmax) of buprenorphine following INDV-6001 100mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state minimum plasma concentration over a dosing interval (Cmin) of buprenorphine following INDV-6001 100mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state plasma concentration measured at the end of the dosing interval (Ctrough) of buprenorphine following INDV-6001 100mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state average plasma concentration over the dosing interval (Cavg) of buprenorphine following INDV-6001 100mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state ratio of peak to trough plasma concentrations over a dosing interval (% fluctuation) of buprenorphine following INDV-6001 100mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 56 days [8 weeks]
measure: Steady-state area under the plasma concentration-time curve over the dosing interval (AUCtau) of buprenorphine following INDV-6001 600mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 112 days [16 weeks]
measure: Steady-state maximum observed plasma concentration (Cmax) of buprenorphine following INDV-6001 600mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 112 days [16 weeks]
measure: Steady-state time to attain the maximum observed plasma concentration (Tmax) of buprenorphine following INDV-6001 600mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 112 days [16 weeks]
measure: Steady-state minimum plasma concentration over a dosing interval (Cmin) of buprenorphine following INDV-6001 600mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 112 days [16 weeks]
measure: Steady-state plasma concentration measured at the end of the dosing interval (Ctrough) of buprenorphine following INDV-6001 600mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 112 days [16 weeks]
measure: Steady-state average plasma concentration over the dosing interval (Cavg) of buprenorphine following INDV-6001 600mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 112 days [16 weeks]
measure: Steady-state ratio of peak to trough plasma concentrations over a dosing interval (% fluctuation) of buprenorphine following INDV-6001 600mg injection in the abdomen Vs SUBLOCADE 100mg injection in the abdomen
timeFrame: Up to 112 days [16 weeks]
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Miami Lakes
country: United States
facility: Innovative Clinical Research, Inc.
state: Florida
city: Chicago
country: United States
facility: Chicago Clinical Research Institute Inc.
state: Illinois
city: Flowood
country: United States
facility: Precise Research Centers
state: Mississippi
city: Marlton
country: United States
facility: Hassman Research Institute (Cenexel HRI - Marlton)
state: New Jersey
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Dayton
country: United States
facility: Midwest Clinical Research
state: Ohio
city: Desoto
country: United States
facility: Insite Clinical Research, LLC
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Village
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research
state: Texas
city: Bountiful
country: United States
facility: Progressive Clinical Research
state: Utah
Study officials:
References: