Study of Potential CYP3A4 Induction by INDV-2000 in Healthy Adults

An Open Label, Fixed-sequence Study to Evaluate the Potential CYP3A4 Induction Effect of INDV-2000 Using Oral Midazolam as a Probe in Healthy Adults Participants

The purpose of this study is to investigate the potential for cytochrome P450 (CYP) 3A4 induction after dosing with INDV-2000 via use of midazolam as a probe.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: INDV-2000; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Participant must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
2. Body weight of a minimum of 50.0 kg at the screening visit and body mass index within the range 18.0 - 32.0 kg/m^2 (inclusive).
3. Male or female who is healthy as determined by medical evaluation.

4. Females will be of non-childbearing potential. Females of non-childbearing potential are considered women who:

   • Do not have a uterus, or
   • Are surgically sterile (eg, has undergone complete hysterectomy, bilateral oophorectomy, hysteroscopic sterilization, or tubal ligation), or
   • Have permanent cessation of ovarian function due to ovarian failure or surgical removal of the ovaries, or
   • Are post-menopausal as defined by 12 months or more of spontaneous amenorrhea as confirmed by a follicle-stimulating hormone (FSH) > 30 mIU/mL
5. Male participants agree to follow contraception guidelines specified in the Protocol.
6. Continuous non-smoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to the first dosing based on participant self-reporting.
7. Capable of giving signed informed consent.

Exclusion Criteria:

1. Have an ongoing medical history of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal (GI) disease, psychiatric or other disorder as judged by an Investigator that could potentially affect the study outcomes or compromise participant safety.
2. Have clinically significant abnormal biochemistry, hematology or urinalysis results as judged by an Investigator.
3. Have a history of narcolepsy or sleep apnea.
4. Have disorders that may interfere with drug absorption, distribution, metabolism and excretion processes.
5. Current active hepatic or biliary disease.
6. Participants with cholecystectomy < 90 days prior to screening.
7. Positive test results for human immunodeficiency virus (HIV)-1/HIV-2 antibodies, Hepatitis B surface antigen (HBsAg) or Hepatitis C antibodies.
8. Have a blood pressure reading outside of the following range: Systolic < 86 or > 149 mmHg; Diastolic < 50 or > 94 mmHg

9. Serious cardiac illness or other medical condition including, but not limited to:

   • Uncontrolled arrhythmias
   • History of congestive heart failure
   • QTcF > 450 msec for males and > 470 msec for females or history of prolonged QT syndrome
   • Myocardial infarction
   • Uncontrolled symptomatic angina
10. 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 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.
11. Healthy participants who are taking, or have taken, any prescribed or over-the-counter drugs (other than 2 grams of acetaminophen per 24-hour period as of Day 1, hormone replacement therapy, or thyroid hormone replacement therapy) or herbal remedies in the 14 days or 5 half-lives (whichever is longer) prior to first dose of study drug.
12. Treatment with any known drugs that are moderate or strong inhibitors/inducers of CYP3A4 or CYP2C19, including St. John's Wort, within 30 days prior to first dose of study drug.
13. Any consumption of food or drink containing poppy seeds, grapefruit or Seville oranges within 14 days prior to the first dose of study drug.
14. Regular alcohol consumption in males > 21 units per week and females > 14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
15. Positive test result for alcohol and/or drugs of abuse at screening or at check-in.
16. Female participant with a positive pregnancy test at the screening visit or at first check-in or who are lactating.
17. Concurrent treatment or treatment with an investigational drug or device within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
18. Blood donation of approximately 500 mL or more within 56 days or plasma donation within 7 days of screening.
19. Known hypersensitivity to INDV-2000 or any other ingredient in the INDV-2000 formulation.
20. Known hypersensitivity to midazolam or any other ingredient in midazolam HCl syrup.
21. Site staff and/or participants who have a financial interest in, or an immediate family member of either the site staff and/or Indivior employees, directly involved in the study.
22. Major surgical procedure (as defined by the Investigator) within 90 days prior to the first dose of study drug or still recovering from prior surgery.
23. Concurrent enrollment in another clinical study, unless it is an observational study.
24. Participants who are unable, in the opinion of the Investigator, to comply fully with the study requirements.
25. Any condition that, in the opinion of the Investigator or Indivior, would interfere with evaluation of the study drug or interpretation of participant safety or study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: INDV-2000 BID + Midazolam; Participants will receive a single oral dose of 5 mg midazolam on Day 1. Participants will receive a dose of INDV-2000 twice a day (BID) from Days 2 to 15. On Day 15 participants will also receive a single oral dose of 5 mg midazolam co-administered with the INDV-2000 morning dose.	Drug: INDV-2000; Capsules administered orally twice a day; Other Names: C4X_3256; Drug: Midazolam; Midazolam syrup administered orally on Days 1 and 15

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Midazolam and 1-hydroxymidazolam	Day 1 and Day 15
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Midazolam and 1-hydroxymidazolam	Day 1 and Day 15
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam and 1-hydroxymidazolam	Day 1 and Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	TEAEs will be defined as adverse events that start on or after the first dose of study drug.	From first dose of study drug to Day 22

Collaborators and Investigators

• Sponsor: Indivior Inc.
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Danielle Armas, MD, Celerion

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2023
• Primary Completion (Actual): April 6, 2023
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: January 12, 2023
• First Submitted That Met QC Criteria: January 12, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2024
• Last Update Submitted That Met QC Criteria: May 24, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: INDV-2000-104; UG3DA050308 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No