A Study to Assess Mass Balance, Pharmacokinetics, Metabolism, and Excretion of Emraclidine in Healthy Adult Male Participants

Healthy Participants Clinical Trial

Official title:

A Phase 1, Open-Label Trial to Assess the Mass Balance, Pharmacokinetics, Metabolism, and Excretion of Emraclidine in Healthy Adult Male Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06301971
• Other study ID #: CVL-231-HV-1011
• Status: Completed
• Phase: Phase 1
• Start date: March 4, 2024
• Est. completion date: April 4, 2024

Study information

• Verified date: May 2024
• Source: Cerevel Therapeutics, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of this study is to determine the mass balance, routes, and rates of elimination of total radioactivity and characterize the pharmacokinetics (PK) of emraclidine, metabolite CV-0000364, and total radioactivity in plasma and whole blood following a single oral dose of [14C]-emraclidine in healthy adult male participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: April 4, 2024
• Est. primary completion date: April 4, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Body mass index (BMI) of 18.5 to 35.0 kilograms per square meters (kg/m^2), inclusive, and a total body weight =50 kg [110 Pounds (lbs)].

2. A male participant who is sexually active with a pregnant or a nonpregnant woman of childbearing potential must agree to use a condom during the trial and for 90 days after the dose of investigational medicinal product (IMP). In addition, male participants should not donate sperm for a minimum of 90 days following the dose of IMP.

3. 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.

4. Capable of consuming the standard diet.

5. History of a minimum of 1 bowel movement per day.

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, Preparatory Acts or 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 IMP or likely to require concomitant therapy. Vaccinations or boosters within 28 days of planned dosing or while on trial.

5. 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.

6. Positive drug screen (including cotinine and tetrahydrocannabinol [THC]) or a positive test for alcohol.

7. 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:

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2× upper limit of 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.

8. Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Emraclidine
Oral solution/suspension

Locations

Country	Name	City	State
United States	Austin, Texas	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Cerevel Therapeutics, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration Time Curve (AUC) from Zero to Infinity (AUCinf) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood		Pre-dose and at multiple time points post-dose up to Day 15
Primary	AUC from Time 0 to last Quantifiable Concentration (AUClast) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Maximum Plasma Concentration (Cmax) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Time to Last Measurable Concentration (Tlast) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Time to Maximum Observed Concentration (Tmax) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Apparent Terminal Elimination Half-life (t½) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Terminal Rate Constant (?z) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Total Plasma Clearance After Oral Administration (CL/F) of Emraclidine		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Emraclidine		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Ratio of Plasma AUCinf for Emraclidine to Plasma AUCinf for Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Ratio of Plasma AUCinf for Metabolite CV-0000364 to Plasma AUCinf for Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Ratio of Plasma AUCinf for Metabolite CV-0000364 to Plasma AUCinf for Emraclidine		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Ratio of Whole Blood AUCinf for Total Radioactivity to Plasma AUCinf for Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Amount Excreted in Urine (Aeu) of Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Cumulative Aeu of Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Percentage Excreted in Urine (feu) of Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Cumulative feu of Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Amount Excreted in Feces (Aef) of Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Cumulative Aef of Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Percentage Excreted in Feces (fef) of Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Cumulative fef of Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Percentage Dose (%Dose) of Total Radioactivity Excreted in Urine Plus Feces Combined		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Cumulative Percentage Dose of Total Radioactivity Excreted in Urine Plus Feces Combined		Pre-dose and at multiple time points post-dose up to Day 15
Secondary	Metabolite Profile of Emraclidine in Plasma, Urine and Feces		Pre-dose and at multiple time points post-dose up to Day 15
Secondary	Structural Identification of Emraclidine Metabolites Found in Plasma, Urine and Feces		Pre-dose and at multiple time points post-dose up to Day 15
Secondary	Number of Participants with Treatment Emergent Adverse Events (TEAEs)		Up to Day 16
Secondary	Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values		Up to Day 15
Secondary	Number of Participants with Clinically Significant Changes in Vital Signs		Up to Day 15
Secondary	Number of Participants with Clinically Significant Changes in Laboratory Assessments		Up to Day 15
Secondary	Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results		Up to Day 15
Secondary	Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score	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 15