A Trial to Evaluate the Effects of Itraconazole and Carbamazepine on the Pharmacokinetics of Emraclidine and of Emraclidine on the Pharmacokinetics of Metformin in Healthy Adult Participants

NCT05965219 | Completed Phase 1 FDA Drug

• 1 other identifier: CVL-231-HV-1010
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of the study is to evaluate the effect of itraconazole, a strong cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of emraclidine and metabolite CV-0000364 in Part A, the effect of carbamazepine, a strong CYP3A4 inducer, on the PK of emraclidine and metabolite CV-0000364 in Part B, and to evaluate the effect of emraclidine on the PK of metformin in Part C in healthy adult participants.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (9)

• Part A: Maximum Observed Plasma Concentration (Cmax) of Emraclidine and its Metabolite CV-0000364

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 15 in TP 2 of Part A

• Part B: Cmax of Emraclidine and its Metabolite CV-0000364

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 20 in TP 2 of Part B

• Part C: Cmax of Metformin

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 11 in TP 2 of Part C

• Part A: Area Under the Plasma Concentration-time Curve from Time Zero to Last Specified Sampling Time (AUC0-t) of Emraclidine and its Metabolite CV-0000364

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 15 in TP 2 of Part A

• Part B: AUC0-t of Emraclidine and its Metabolite CV-0000364

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 20 in TP 2 of Part B

• Part C: AUC0-t of Metformin

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 11 in TP 2 of Part C

• Part A: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Emraclidine and its Metabolite CV-0000364

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 15 in TP 2 of Part A

• Part B: AUCinf of Emraclidine and its Metabolite CV-0000364

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 20 in TP 2 of Part B

• Part C: AUCinf of Metformin

  Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 11 in TP 2 of Part C

Secondary Outcomes (6)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) Based on Severity

  From the first dose up to 1 month following last dose with investigational medicinal product (IMP) in each part of the study

• Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values

  Up to end of treatment in each part of the study (up to an average of 15 days)

• Number of Participants With Clinically Significant Changes in Vital Sign Measurements

  Up to end of treatment in each part of the study (up to an average of 15 days)

• Number of Participants With Clinically Significant Changes in Laboratory Assessments

  Up to end of treatment in each part of the study (up to an average of 15 days)

• Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results

  Up to end of treatment in each part of the study (up to an average of 15 days)

Study Arms (3)

Part A: Emraclidine Followed by Itraconazole + Emraclidine

EXPERIMENTAL

Participants will receive a single oral dose of emraclidine 10 milligrams (mg) on Day 1 in Treatment Period (TP) 1 followed by itraconazole 200 mg, orally, twice daily (BID) on Day 1 and once daily (QD) from Days 2 to 14, with a single oral dose of emraclidine 10 mg co-administered on Day 5 in TP 2.

Drug: Emraclidine; Drug: Itraconazole

Part B: Emraclidine Followed by Carbamazepine + Emraclidine

EXPERIMENTAL

Participants will receive a single oral dose of emraclidine 30 mg on Day 1 in TP 1 followed by carbamazepine 100 mg BID from Days 1 to 3, 200 mg BID from Days 4 to 6, and 300 mg BID from Days 7 to 19, orally, with a single oral dose of emraclidine 30 mg on Day 16 in TP 2.

Drug: Emraclidine; Drug: Carbamazepine

Part C: Metformin Followed by Emraclidine + Metformin

EXPERIMENTAL

Participants will receive a single oral dose of metformin 850 mg on Day 1 in TP 1 followed by emraclidine 30 mg, orally, QD for Days 1 to 10, with a single oral dose of metformin 850 mg co-administered on Day 8 in TP 2.

Drug: Emraclidine; Drug: Metformin

Interventions

Emraclidine DRUG

Emraclidine tablets.

Part A: Emraclidine Followed by Itraconazole + Emraclidine; Part B: Emraclidine Followed by Carbamazepine + Emraclidine; Part C: Metformin Followed by Emraclidine + Metformin

Itraconazole DRUG

Itraconazole oral solution.

Also known as: Sporanox

Part A: Emraclidine Followed by Itraconazole + Emraclidine

Carbamazepine DRUG

Carbamazepine tablets.

Also known as: Tegretol-XR

Part B: Emraclidine Followed by Carbamazepine + Emraclidine

Metformin DRUG

Metformin tablets.

Also known as: Glucophage

Part C: Metformin Followed by Emraclidine + Metformin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator.
• Body mass index of 18.5 to 35.0 kilograms per square meter (kg/m\^2), inclusive, and a total body weight ≥50 kilograms (kg) (110 pounds \[lbs\]).
• Male and female (women of nonchildbearing potential only) participants, ages 18 to 55 years, inclusive, at the time of signing the informed consent form (ICF).
• Male and female (women of nonchildbearing potential only) participants, ages 18 to 55 years, inclusive, at the time of signing the ICF.
• Male and female (both women of childbearing and nonchildbearing potential) participants, ages 18 to 55 years, inclusive, at the time of signing the ICF.
• Sexually active women of childbearing potential must agree to use at least an acceptable birth control method during the trial and for 7 days after the last dose of IMP. Acceptable birth control methods that result in a failure rate of more than 1% per year include the following:
• Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action
• Male or female condom with or without spermicide
• Cap, diaphragm, or sponge with spermicide

You may not qualify if:

• Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus, thyroid disorders), malignancy, hematological, immunological, neurological, or psychiatric disease that, in the opinion of the investigator or medical monitor, could compromise either participant safety or the results of the trial.
• "Yes" responses for any of the following items on the C-SSRS (within the individual's lifetime):
• Suicidal Ideation Item 3 (Active Suicidal Ideation With Any Methods \[Not Plan\] Without Intent to Act)
• Suicidal Ideation Item 4 (Active Suicidal Ideation With Some Intent to Act, Without Specific Plan)
• Suicidal Ideation Item 5 (Active Suicidal Ideation With Specific Plan and Intent)
• Any of the Suicidal Behavior items (Actual Attempt, Interrupted Attempt, Aborted Attempt, or Preparatory Acts/Behavior)
• "Yes" responses for any of the following items on the C-SSRS (within past 12 months):
• Suicidal Ideation Item 1 (Wish to be Dead)
• Suicidal Ideation Item 2 (Non-Specific Active Suicidal Thoughts)
• Any condition or surgery that could possibly affect drug absorption, including, but not limited to, bowel resections, bariatric weight loss surgery/procedures, gastrectomy, and cholecystectomy.
• Positive result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B total core antibody, or hepatitis C antibody with detectable viral ribonucleic acid (RNA) levels at Screening.
• Positive drug screen (including cotinine and tetrahydrocannabinol \[THC\]) or a positive test for alcohol.
• History of presence of any of the following and deemed clinically significant by the investigator or designee and confirmed by the medical monitor:
• Ventricular dysfunction or risk factors for torsades de pointes (e.g., heart failure, cardiomyopathy, family history of long-QT syndrome)
• Any of the following clinical laboratory test results at the Screening Visit or Check-in (Day -1), which can be confirmed by a single repeat measurement, if deemed necessary:

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead

Study Sites (1)

Overland Park, Kansas

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Interventions

Itraconazole; Carbamazepine; Metformin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2023
• First Posted: July 28, 2023
• Study Start: August 15, 2023
• Primary Completion: November 10, 2023
• Study Completion: November 10, 2023
• Last Updated: April 2, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)