Study to Assess Repeated Doses of INDV-2000 in Healthy Volunteers and in Treatment Seeking Individuals With Opioid Use Disorder

NCT04976855 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: INDV-2000-102UG3DA050308
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objectives for the study are:

• Part I and Part II: Assess safety and tolerability of repeated doses of INDV-2000 in healthy volunteers.
• Part III: Assess the safety and tolerability of repeated doses of INDV-2000 administered alone and with SUBOXONE sublingual (SL) film in an opioid use disorder (OUD) treatment seeking population.

Conditions

Healthy Volunteer; Opioid-use Disorder

Outcome Measures

Primary Outcomes (2)

• Part I and Part II: Number of Participants With Adverse Events

  From first dose of study drug up to 7 days after last dose (up to 14 days in Part I and 35 days in Part II).

• Part III: Number of Participants With Adverse Events

  From first dose of INDV-2000 up to 7 days after last dose (up to 18 days).

Secondary Outcomes (3)

• Part I and Part II: Maximum Plasma Concentration (Cmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II

  Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

• Part I and Part II: Time to Maximum Plasma Concentration (Tmax) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II

  Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

• Part I and Part II: Area Under the Plasma Concentration-time Curve (AUC0-τ) of INDV-2000 Following Dosing on Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II

  Days 1 and 7 for Part I and Days 1, 7, and 28 for Part II, predose and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose

Study Arms (9)

Part I Cohort 1 INDV-2000 100 mg QD

EXPERIMENTAL

Healthy volunteers will receive INDV-2000 100 mg once daily for 7 days.

Drug: INDV-2000

Part I Cohort 1 Placebo

PLACEBO COMPARATOR

Healthy volunteers will receive placebo once daily for 7 days.

Drug: Placebo

Part I Cohort 2 INDV-2000 100 mg BID

EXPERIMENTAL

Healthy volunteers will receive INDV-2000 100 mg twice daily for 7 days.

Drug: INDV-2000

Part I Cohort 2 Placebo

PLACEBO COMPARATOR

Healthy volunteers will receive placebo twice daily for 7 days.

Drug: Placebo

Part II Cohort 1 INDV-2000 200 mg BID

EXPERIMENTAL

Healthy volunteers will receive INDV-2000 200 mg twice daily for 28 days.

Drug: INDV-2000

Part II Cohort 1 Placebo

PLACEBO COMPARATOR

Healthy volunteers will receive placebo twice daily for 28 days.

Drug: Placebo

Part II Cohort 2 INDV-2000 400 mg BID

EXPERIMENTAL

Healthy volunteers will receive INDV-2000 400 mg twice daily for 28 days.

Drug: INDV-2000

Part II Cohort 2 Placebo

PLACEBO COMPARATOR

Healthy volunteers will receive placebo twice daily for 28 days.

Drug: Placebo

Part III INDV-2000 400 mg BID + SUBOXONE SL Film

EXPERIMENTAL

Participants with opioid use disorder will receive SUBOXONE sublingual (SL) film for 6 days during the run-in period. Participants will then receive SUBOXONE SL film alone for 2 days, then SUBOXONE SL film and INDV-2000 for 7 days followed by INDV-2000 dosing alone for 4 days.

Drug: INDV-2000; Drug: SUBOXONE® sublingual film

Interventions

INDV-2000 DRUG

Capsule for oral administration

Also known as: C4X_3256

Part I Cohort 1 INDV-2000 100 mg QD; Part I Cohort 2 INDV-2000 100 mg BID; Part II Cohort 1 INDV-2000 200 mg BID; Part II Cohort 2 INDV-2000 400 mg BID; Part III INDV-2000 400 mg BID + SUBOXONE SL Film

Placebo DRUG

Capsule for oral administration

Part I Cohort 1 Placebo; Part I Cohort 2 Placebo; Part II Cohort 1 Placebo; Part II Cohort 2 Placebo

SUBOXONE® sublingual film DRUG

Administered either under the tongue (sublingual) or between the gum and cheek (buccal)

Also known as: Buprenorphine and naloxone

Part III INDV-2000 400 mg BID + SUBOXONE SL Film

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures, be able to comply with protocol requirements, rules and regulations of study site, and be likely to complete all the study interventions.
• Female subjects of child-bearing potential who are sexually active with males must use, with their partner, a condom plus an approved method of effective contraception from the time of screening until 30 days after the last dose of Investigational Medicinal Product (IMP). The impact of IMP on the efficacy of hormonal contraceptives is unknown. Male subjects who are sexually active with female partners of child-bearing potential must use, with their partner, a condom plus an approved method of effective contraception from the time of screening until 90 days after the last dose of IMP and agree to not donate sperm over this time period. Effective methods of contraception are:
• Combined (estrogen and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
• Progestogen-only hormonal contraception: oral, injectable/implantable, or intrauterine hormone-releasing system (IUD)
• Implantable intrauterine device (IUS)
• Surgical sterilization (for example, vasectomy or bilateral tubal ligation)
• Male condom with spermicidal gel/foam or with female cap or diaphragm (double barrier)
• abstinence from heterosexual intercourse as a conscious choice and established pattern of lifestyle
• Part I and II only:
• Healthy male or female.
• Between 18 and 55 years of age inclusive.
• Body mass index (BMI) within 18.0 to 32.0 kg/m\^2, inclusive (minimum weight of at least 50.0 kg at Screening).
• Part III only:
• Male or female seeking treatment for OUD with a diagnosis of moderate or severe OUD by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria.
• Between 18 and 65 years of age inclusive.

You may not qualify if:

• Have a medical history of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder as judged by an Investigator.
• Have clinically significant abnormal biochemistry, hematology or urinalysis results as judged by an Investigator or medically responsible physician.
• Have a history of narcolepsy or other significant sleep disorders.
• Have disorders that may interfere with drug absorption, distribution, metabolism and excretion (ADME) processes.
• Positive test results for human immunodeficiency virus (HIV)-1/HIV-2 antibodies, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb).
• Serious cardiac illness or other cardiac assessments including, but not limited to:
• Uncontrolled arrhythmias.
• History of congestive heart failure (CHF).
• Myocardial infarction \<6 months from receipt of first dose of IMP
• Uncontrolled symptomatic angina
• QTcF \> 450 msec for males and \> 470 msec for females or history of prolonged QT syndrome.
• Current active hepatic or biliary disease, including subjects with cholecystectomy \<90 days prior to Screening.
• Concurrent treatment or treatment with an investigational drug within 30 days prior to the first dose of any study drug.
• History of suicidal ideation within 30 days prior to providing written informed consent as evidenced by answering "yes' to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at the Screening Visit or history of a suicide attempt (per the C-SSRS) in the 6 months prior to informed consent.
• Pregnant or lactating females.

Sponsors & Collaborators

• Indivior Inc.: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (3)

Johns Hopkins University School of Medicine BPRU

Baltimore, Maryland, 21224, United States

Location

InSite Clinical Research

DeSoto, Texas, 75115, United States

Location

Worldwide Clinical Trials

San Antonio, Texas, 78217, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Buprenorphine; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Naloxone; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Global Director Clinical Development
• Organization: Indivior Inc.

trialdisclosure@indivior.com

(804) 594-4488

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2021
• First Posted: July 26, 2021
• Study Start: August 17, 2022
• Primary Completion: July 5, 2023
• Study Completion: July 5, 2023
• Last Updated: August 21, 2024
• Results First Posted: August 21, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)