A Study Evaluating the Pharmacokinetics and Relative Bioavailability of Emraclidine Immediate-Release Tablets in Healthy Adult Participants

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate plasma concentrations of emraclidine following single dose oral administration of different emraclidine immediate release (IR) tablets in healthy participants.

Official Title
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A Phase 1, Open-label Trial to Evaluate the Pharmacokinetics and Relative Bioavailability of Emraclidine Following a Single Oral Administration of Immediate-Release Tablets in Healthy Adult Participants

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Treatment A: Emraclidine 30mg IR tablets (reference)
* Drug: Treatment B: Emraclidine 30mg IR test tablets 1
* Drug: Treatment C: Emraclidine 30mg IR test tablets 2
* Drug: Treatment D: Emraclidine 30mg IR test tablets 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 investigational medicinal product (IMP) Body mass index of 18.5 to 35.0 kilogram/meter square (kg/m^2), inclusive, and a total body weight ≥50 kg 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 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: 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) Serious risk of suicide in the opinion of the investigator is also exclusionary 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 Female participants who are pregnant, breastfeeding, or planning to become pregnant during IMP treatment or within 7 days after the last dose of IMP Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients Received IMP in a clinical trial of emraclidine NOTE: Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a 4-period, 4-sequence crossover study. The 4 treatments are A- 30 milligrams (mg) emraclidine IR tablets (reference); B- 30 mg emraclidine IR test tablets 1; C- 30 mg emraclidine IR test tablets 2; D- 30 mg emraclidine IR test tablets 3. Participants will be randomized to 1 of 4 treatment sequences. Each participant will be administered each of the 4 treatments exactly once, i.e.,1 treatment per period and there will be a 7 day washout period between each treatment.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: A-B-C-D<br>Participants will receive emraclidine, 30 mg IR tablets, in the treatment sequence A-B-C-D orally, on Day 1 of each 5-day treatment period (up to 26 days) | Drug: Treatment A: Emraclidine 30mg IR tablets (reference)<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment B: Emraclidine 30mg IR test tablets 1<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment C: Emraclidine 30mg IR test tablets 2<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment D: Emraclidine 30mg IR test tablets 3<br>* IR oral tablets<br>* Other names: CVL-231;|
| Experimental: Sequence 2: B-C-D-A<br>Participants will receive emraclidine, 30 mg IR tablets, in the treatment sequence B-C-D-A orally, on Day 1 of each 5-day treatment period (up to 26 days) | Drug: Treatment A: Emraclidine 30mg IR tablets (reference)<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment B: Emraclidine 30mg IR test tablets 1<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment C: Emraclidine 30mg IR test tablets 2<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment D: Emraclidine 30mg IR test tablets 3<br>* IR oral tablets<br>* Other names: CVL-231;|
| Experimental: Sequence 3: C-D-A-B<br>Participants will receive emraclidine, 30 mg IR tablets, in the treatment sequence C-D-A-B orally, on Day 1 of each 5-day treatment period (up to 26 days) | Drug: Treatment A: Emraclidine 30mg IR tablets (reference)<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment B: Emraclidine 30mg IR test tablets 1<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment C: Emraclidine 30mg IR test tablets 2<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment D: Emraclidine 30mg IR test tablets 3<br>* IR oral tablets<br>* Other names: CVL-231;|
| Experimental: Sequence 4: D-A-B-C<br>Participants will receive emraclidine, 30 mg IR tablets, in the treatment sequence D-A-B-C orally, on Day 1 of each 5-day treatment period (up to 26 days) | Drug: Treatment A: Emraclidine 30mg IR tablets (reference)<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment B: Emraclidine 30mg IR test tablets 1<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment C: Emraclidine 30mg IR test tablets 2<br>* IR oral tablets<br>* Other names: CVL-231;Drug: Treatment D: Emraclidine 30mg IR test tablets 3<br>* IR oral tablets<br>* Other names: CVL-231;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of Emraclidine |  | Predose and up to 96 hours post dose in each treatment period | 
| Time to Maximum Plasma Concentration (Tmax) of Emraclidine |  | Predose and up to 96 hours post dose in each treatment period | 
| Area Under the Plasma Concentration-time Curve From Time 0 to the time of Last Quantifiable Concentration (AUC0-t) of Emraclidine |  | Predose and up to 96 hours post dose in each treatment period | 
| Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of Emraclidine |  | Predose and up to 96 hours post dose in each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment Emergent Adverse Events (TEAEs) |  | Up to approximately 4 months | 
| Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Results |  | Up to approximately 4 months | 
| Number of Participants With Clinically Significant Changes in Vital Sign Values |  | Up to approximately 4 months | 
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Assessments |  | Up to approximately 4 months | 
| Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results |  | Screening up to checkout (up to approximately 4 months) | 
| Changes in Suicidality as Assessed by 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 approximately 4 months |