A Phase I Double-Blind, Placebo-Controlled Randomized Study to Assess Repeated Doses of INDV-2000 (C4X_3256) up to 28 Days in Healthy Volunteers, and an Open-Label Study of INDV-2000 up to 11 Days in Treatment Seeking Individuals With Opioid Use Disorder
Overview
- Phase
- Phase 1
- Intervention
- INDV-2000
- Conditions
- Healthy Volunteer
- Sponsor
- Indivior Inc.
- Enrollment
- 64
- Locations
- 3
- Primary Endpoint
- Part I and Part II: Number of Participants With Adverse Events
- Status
- Completed
- Last Updated
- last year
Overview
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.
Detailed Description
The study will be conducted in 3 parts: Part I: Double-blind, placebo-controlled, randomized, multiple ascending dose study for 7 days of dosing with INDV-2000 in healthy volunteers. Part II: Double-blind, placebo-controlled, randomized, multiple ascending dose study for 28 days of dosing with INDV-2000 in healthy volunteers. Part III: This part is an open-label study in OUD treatment seeking individuals.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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
Arms & Interventions
Part I Cohort 1 INDV-2000 100 mg QD
Healthy volunteers will receive INDV-2000 100 mg once daily for 7 days.
Intervention: INDV-2000
Part I Cohort 1 Placebo
Healthy volunteers will receive placebo once daily for 7 days.
Intervention: Placebo
Part I Cohort 2 INDV-2000 100 mg BID
Healthy volunteers will receive INDV-2000 100 mg twice daily for 7 days.
Intervention: INDV-2000
Part I Cohort 2 Placebo
Healthy volunteers will receive placebo twice daily for 7 days.
Intervention: Placebo
Part II Cohort 1 INDV-2000 200 mg BID
Healthy volunteers will receive INDV-2000 200 mg twice daily for 28 days.
Intervention: INDV-2000
Part II Cohort 1 Placebo
Healthy volunteers will receive placebo twice daily for 28 days.
Intervention: Placebo
Part II Cohort 2 INDV-2000 400 mg BID
Healthy volunteers will receive INDV-2000 400 mg twice daily for 28 days.
Intervention: INDV-2000
Part II Cohort 2 Placebo
Healthy volunteers will receive placebo twice daily for 28 days.
Intervention: Placebo
Part III INDV-2000 400 mg BID + SUBOXONE SL Film
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.
Intervention: INDV-2000
Part III INDV-2000 400 mg BID + SUBOXONE SL Film
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.
Intervention: SUBOXONE® sublingual film
Outcomes
Primary Outcomes
Part I and Part II: Number of Participants With Adverse Events
Time Frame: 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
Time Frame: From first dose of INDV-2000 up to 7 days after last dose (up to 18 days).
Secondary Outcomes
- 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)