The Effect of Food on the Pharmacokinetics (PK) of Emraclidine in Healthy Adult Participants

A Phase 1, Open-label Trial to Evaluate the Effect of Food on the Pharmacokinetics of Emraclidine in Healthy Adult Participants

The primary purpose of this study is to evaluate the effect of food (a high-fat meal) on the pharmacokinetics of emraclidine and metabolite CV-0000364 following single oral dose administration in healthy adult participants.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Emraclidine

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

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Dilworth, Minnesota, United States, 56529
      • Dilworth, Minnesota

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male and female (both women of childbearing and nonchildbearing potential) participants, ages 18 to 55 years, at the time of signing the informed consent form (ICF).

2. Sexually active women of childbearing potential must agree to use an acceptable birth control method, during the trial and for 7 days after the last dose. 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
3. Body mass index of 17.5 to 32.0 kilograms per square meter (kg/m^2), inclusive, and total body weight >45 kg (110 pounds [lb]) at Screening.
4. 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.
5. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the full protocol.
6. Ability, in the opinion of the investigator, to understand the nature of the trial and comply with protocol requirements, including the prescribed dosage regimens, scheduled visits, laboratory tests, and other trial procedures.

Exclusion Criteria:

1. 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.

2. "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) Serious risk of suicide in the opinion of the investigator is also exclusionary
3. 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.
4. Use of any prescription and over-the-counter medications from 28 days prior to first dose of Investigational Medical Product or likely to require concomitant therapy (e.g., prescription and over-the counter medications, herbal medications, vitamins, and supplements) during the trial, with the exception of acetaminophen (maximum total daily dose of 2 g) and topical hydrocortisone as needed for treatment of an Adverse Event(AE). Vaccinations or boosters within 7 days of planned dosing or while on trial are prohibited.
5. Positive result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C antibody with detectable viral ribonucleic acid (RNA) levels at Screening.
6. Positive drug screen or a positive test for alcohol at Screening or Baseline Visits.
7. Female participants who are pregnant, breastfeeding, or planning to become pregnant during IMP treatment or within 7 days after the last dose of IMP. Women of childbearing potential must have a negative serum pregnancy test result at the Screening Visit and a negative urine pregnancy test result at baseline.

8. Any of the following clinical laboratory test results at the Screening Visit (as assessed by the central laboratory) and at Check-in (Day -1; as assessed by the local laboratory), and confirmed by a single repeat measurement, if deemed necessary:

   • aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.0 × upper limit normal (ULN)
   • Total bilirubin >1.5 × ULN. If Gilbert's syndrome is suspected, total bilirubin >1.5 × ULN is acceptable if the conjugated or direct bilirubin fraction is <20% of total bilirubin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Emraclidine (Fasted then Fed); Single oral dose of Emraclidine 15 mg tablet under fasted (without food) condition followed by fed condition in treatment period 1 and 2, respectively.	Drug: Emraclidine; Tablets
Experimental: Emraclidine (Fed then Fasted); Single oral dose of Emraclidine 15 mg tablet under fed condition followed by fasted (without food) condition in treatment period 1 and 2, respectively.	Drug: Emraclidine; Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Emraclidine and its Metabolite CV-0000364	Pre-dose and at multiple timepoints up to Day 6
Time to Maximum Plasma Concentration (Tmax) of Emraclidine and its Metabolite CV-0000364	Pre-dose and at multiple timepoints up to Day 6
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 timepoints up to Day 6
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 timepoints up to Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)		Up to Day 13
Number of Participants With Clinically Significant Changes in Vital Sign Measurements		Up to Day 13
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters		Up to Day 13
Number of Participants With Clinically Significant Changes in Laboratory Assessments		Up to Day 13
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results		Up to Day 13
Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)	The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the behavior subscale) indicates increased risk.	Up to Day 13

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2023
• Primary Completion (Estimated): August 31, 2023
• Study Completion (Estimated): August 31, 2023

Study Registration Dates

• First Submitted: June 13, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 23, 2023

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: CVL-231-HV-1009

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