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

NCT06301971 | Completed Phase 1 FDA Drug

• 1 other identifier: CVL-231-HV-1011
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (23)

• 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

• 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

• 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

• 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

• 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

• 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

• Terminal Rate Constant (λz) 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

• Total Plasma Clearance After Oral Administration (CL/F) of Emraclidine

  Pre-dose and at multiple time points post-dose up to Day 15

• 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

• 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

• 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

• 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

• 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

• Amount Excreted in Urine (Aeu) of Total Radioactivity

  Pre-dose and at multiple time points post-dose up to Day 15

• Cumulative Aeu of Total Radioactivity

  Pre-dose and at multiple time points post-dose up to Day 15

• Percentage Excreted in Urine (feu) of Total Radioactivity

  Pre-dose and at multiple time points post-dose up to Day 15

• Cumulative feu of Total Radioactivity

  Pre-dose and at multiple time points post-dose up to Day 15

• Amount Excreted in Feces (Aef) of Total Radioactivity

  Pre-dose and at multiple time points post-dose up to Day 15

• Cumulative Aef of Total Radioactivity

  Pre-dose and at multiple time points post-dose up to Day 15

• Percentage Excreted in Feces (fef) of Total Radioactivity

  Pre-dose and at multiple time points post-dose up to Day 15

• Cumulative fef of Total Radioactivity

  Pre-dose and at multiple time points post-dose up to Day 15

• 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

• 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 Outcomes (8)

• Metabolite Profile of Emraclidine in Plasma, Urine and Feces

  Pre-dose and at multiple time points post-dose up to Day 15

• Structural Identification of Emraclidine Metabolites Found in Plasma, Urine and Feces

  Pre-dose and at multiple time points post-dose up to Day 15

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  Up to Day 16

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

  Up to Day 15

• Number of Participants with Clinically Significant Changes in Vital Signs

  Up to Day 15

Study Arms (1)

Emraclidine 30 mg

EXPERIMENTAL

Participants will receive a single oral dose of 30 milligrams (mg) (approximately 75 microcurie \[μCi\]) \[14C\]-emraclidine on Day 1.

Drug: Emraclidine

Interventions

Emraclidine DRUG

Oral solution/suspension

Also known as: CVL-231

Emraclidine 30 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Gender Eligibility Details: U.S. Food and Drug Administration (FDA) recommends that radiation exposure to participants should be kept as low as is reasonably achievable; and since there is no available data to suggest metabolism of the emraclidine is different in women versus men. Hence, female participants are excluded from this study.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 \[110 Pounds (lbs)\].
• 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.
• 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.
• Capable of consuming the standard diet.
• History of a minimum of 1 bowel movement per day.

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, 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)
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead

Study Sites (1)

Austin, Texas

Austin, Texas, 78744, United States

Location

Study Design

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

Study Record Dates

• First Submitted: March 1, 2024
• First Posted: March 8, 2024
• Study Start: March 4, 2024
• Primary Completion: April 4, 2024
• Study Completion: April 4, 2024
• Last Updated: May 2, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)