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

Phase 1
Completed
Conditions
Healthy Participants
Interventions
Registration Number
NCT06435923
Lead Sponsor
Cerevel Therapeutics, LLC
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
8
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Darigabat[14C]-darigabatParticipants will receive a single oral dose of darigabat.
Primary Outcome Measures
NameTimeMethod
AUC from Time 0 to the Time of the Last Measured Concentration (AUClast) of DarigabatPre-dose and at multiple time points post-dose up to Day 15
Maximum Observed Plasma Concentration (Cmax) of DarigabatPre-dose and at multiple time points post-dose up to Day 15
Apparent Total Clearance After Oral Administration (CL/F) of DarigabatPre-dose and at multiple time points post-dose up to Day 15
Amount Excreted in Urine (Aeu) of Total RadioactivityPre-dose and at multiple time points post-dose up to Day 15

Urine PK parameters will be assessed.

Terminal Phase Half-life (t½) of DarigabatPre-dose and at multiple time points post-dose up to Day 15
Ratio of Plasma AUCinf for Darigabat to Total RadioactivityPre-dose and at multiple time points post-dose up to Day 15
Area Under the Concentration Time Curve (AUC) from Time Zero to Infinity (AUCinf) of DarigabatPre-dose and at multiple time points post-dose up to Day 15
Time to Last Quantifiable (Tlast) Concentration of DarigabatPre-dose and at multiple time points post-dose up to Day 15
Time to Maximum Observed Concentration (Tmax) of DarigabatPre-dose and at multiple time points post-dose up to Day 15
Apparent Volume of Distribution During the Terminal Phase (Vz/F) of DarigabatPre-dose and at multiple time points post-dose up to Day 15
Ratio of Whole Blood AUCinf for Total Radioactivity to Plasma Total RadioactivityPre-dose and at multiple time points post-dose up to Day 15
Amount Excreted in Feces (Aef) of Total RadioactivityPre-dose and at multiple time points post-dose up to Day 15

Fecal PK parameters will be assessed.

Secondary Outcome Measures
NameTimeMethod
Structural Elucidation of [14C]-darigabat Metabolites ≥10% of the Total [14C]-darigabat Radioactivity Found in Plasma, Urine and FecesPre-dose and at multiple time points post-dose up to Day 15
Number of Participants with Clinically Significant Changes in Vital SignsUp to Day 15
Metabolite Profile of [14C]-darigabat in Plasma, Urine and FecesPre-dose and at multiple time points post-dose up to Day 15
Identification of [14C]-darigabat Metabolites Found in Plasma, Urine and FecesPre-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 Laboratory AssessmentsUp to Day 15
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) ValuesUp to Day 15
Number of Participants with Clinically Significant Changes in Physical and Neurological Examination ResultsUp to Day 15

Trial Locations

Locations (1)

Austin, Texas

🇺🇸

Austin, Texas, United States

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