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

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06435923
• Other study ID #: CVL-865-HV-1004
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 2024
• Est. completion date: July 2024

Study information

• Verified date: May 2024
• Source: Cerevel Therapeutics, LLC
• Contact: Cerevel Clinical Trial Support
• Email: cerevelclinicaltrials[@]cerevel.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 8
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• [14C]-darigabat
Oral capsule

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 Time Zero to Infinity (AUCinf) of Darigabat		Pre-dose and at multiple time points post-dose up to Day 15
Primary	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
Primary	Maximum Observed Plasma Concentration (Cmax) of Darigabat		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Time to Last Quantifiable (Tlast) Concentration of Darigabat		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Time to Maximum Observed Concentration (Tmax) of Darigabat		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Terminal Phase Half-life (t½) of Darigabat		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Apparent Total Clearance After Oral Administration (CL/F) of Darigabat		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 Darigabat		Pre-dose and at multiple time points post-dose up to Day 15
Primary	Ratio of Plasma AUCinf for Darigabat to Total Radioactivity		Pre-dose and at multiple time points post-dose up to Day 15
Primary	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
Primary	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
Primary	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	Metabolite Profile of [14C]-darigabat in Plasma, Urine and Feces		Pre-dose and at multiple time points post-dose up to Day 15
Secondary	Identification of [14C]-darigabat Metabolites Found in Plasma, Urine and Feces		Pre-dose and at multiple time points post-dose up to Day 15
Secondary	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
Secondary	Number of Participants with Adverse Events (AEs)		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