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

A Phase 1, Open-Label Trial to Assess the Absorption, Metabolism, Excretion, and Mass Balance of [14C]-Darigabat Following a Single Oral Dose in Healthy Adult Male Participants

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.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: [14C]-darigabat

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • Austin, Texas

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 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.
2. 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.
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.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Darigabat; Participants will receive a single oral dose of darigabat.	Drug: [14C]-darigabat; Oral capsule; Other Names: CVL-865; PF-06372865

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Number of Participants with Clinically Significant Changes in Laboratory Assessments	Up to Day 15
Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results	Up to Day 15
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

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2024
• Primary Completion (Actual): July 2, 2024
• Study Completion (Actual): July 3, 2024

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): July 31, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; GABA Modulators; GABA Agents; PF-06372865
• Other Study ID Numbers: CVL-865-HV-1004

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