Healthy Participants
Conditions
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.
Interventions
DRUG[14C]-darigabat
Oral capsule
Sponsors
Cerevel Therapeutics, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Amount Excreted in Feces (Aef) of Total Radioactivity | Pre-dose and at multiple time points post-dose up to Day 15 | Fecal PK parameters will be assessed. |
| 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 | Pre-dose and at multiple time points post-dose up to Day 15 | Urine PK parameters will be assessed. |
| 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Number of Participants with Clinically Significant Changes in Vital Signs | Up to Day 15 |
| Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results | Up to Day 15 |
| Number of Participants with Clinically Significant Changes in Laboratory Assessments | Up to Day 15 |
Countries
United States
Outcome results
None listed