A Trial to Assess the Absorption, Metabolism, Excretion, and Mass Balance of [14C]-Darigabat After a Single Oral Dose in Healthy Male Participants

NCT06435923 | Completed Phase 1 FDA Drug

• 1 other identifier: CVL-865-HV-1004
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Participants

Outcome Measures

Primary Outcomes (12)

• Area Under the Concentration Time Curve (AUC) from Time Zero to Infinity (AUCinf) of Darigabat

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

• AUC from Time 0 to the Time of the Last Measured Concentration (AUClast) of Darigabat

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

• Maximum Observed Plasma Concentration (Cmax) of Darigabat

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

• Time to Last Quantifiable (Tlast) Concentration of Darigabat

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

• Time to Maximum Observed Concentration (Tmax) of Darigabat

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

• Terminal Phase Half-life (t½) of Darigabat

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

• Apparent Total Clearance After Oral Administration (CL/F) of Darigabat

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

• Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Darigabat

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

• Ratio of Plasma AUCinf for Darigabat to Total Radioactivity

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

• Ratio of Whole Blood AUCinf for Total Radioactivity to Plasma Total Radioactivity

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

• Amount Excreted in Urine (Aeu) of Total Radioactivity

  Urine PK parameters will be assessed.

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

• Amount Excreted in Feces (Aef) of Total Radioactivity

  Fecal PK parameters will be assessed.

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

Secondary Outcomes (8)

• Metabolite Profile of [14C]-darigabat in Plasma, Urine and Feces

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

• Identification of [14C]-darigabat Metabolites Found in Plasma, Urine and Feces

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

• Structural Elucidation of [14C]-darigabat Metabolites ≥10% of the Total [14C]-darigabat Radioactivity Found in Plasma, Urine and Feces

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

• Number of Participants with Adverse Events (AEs)

  Up to Day 16

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

  Up to Day 15

Study Arms (1)

Darigabat

EXPERIMENTAL

Participants will receive a single oral dose of darigabat.

Drug: [14C]-darigabat

Interventions

[14C]-darigabat DRUG

Oral capsule

Also known as: CVL-865; PF-06372865

Darigabat

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 there is no available data to suggest metabolism of the darigabat 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 of 18.5 to 35.0 kilograms per square meters (kg/m\^2), inclusive, and a total body weight ≥50 kg \[110 Pounds (lbs)\] at Screening.
• A male participant who is sexually active with a pregnant or a nonpregnant partner of childbearing potential must agree to use a condom during the trial and for 93 days after the dose of investigational medicinal product (IMP). In addition, male participants should not donate sperm for a minimum of 93 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.

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 Columbia-Suicide Severity Rating Scale (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.
• Positive result for human immunodeficiency viruses (HIV) antibody, hepatitis B surface antigen, hepatitis B total core antibody, or hepatitis C antibody with detectable viral Ribonucleic acid (RNA) levels at Screening. Note: Positive or indeterminate test result for hepatitis C antibody should follow with hepatitis C virus polymerase chain reaction (PCR) RNA test. If result is positive, the participant is excluded.
• Positive drug screen \[including cotinine and Tetrahydrocannabinol (THC)\] or a positive test for alcohol.
• Known allergy or hypersensitivity to the IMP, closely related compounds, or any of their specified ingredients.

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead

Study Sites (1)

Austin, Texas

Austin, Texas, 78744, United States

Location

MeSH Terms

Interventions

PF-06372865

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: May 24, 2024
• First Posted: May 30, 2024
• Study Start: May 29, 2024
• Primary Completion: July 2, 2024
• Study Completion: July 3, 2024
• Last Updated: July 31, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)