Clinical trial NCT06435923: A Trial to Assess the Absorption, Metabolism, Excretion, and Mass Balance of [14C]-Darigabat After a Single Oral Dose in Healthy Male Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Lead sponsor: Cerevel Therapeutics, LLC
Sponsor class: INDUSTRY
First posted: 2024-05-30
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Area Under the Concentration Time Curve (AUC) from Time Zero to Infinity (AUCinf) of Darigabat
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: AUC from Time 0 to the Time of the Last Measured Concentration (AUClast) of Darigabat
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Maximum Observed Plasma Concentration (Cmax) of Darigabat
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Time to Last Quantifiable (Tlast) Concentration of Darigabat
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Time to Maximum Observed Concentration (Tmax) of Darigabat
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Terminal Phase Half-life (t½) of Darigabat
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Apparent Total Clearance After Oral Administration (CL/F) of Darigabat
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of Darigabat
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Ratio of Plasma AUCinf for Darigabat to Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Ratio of Whole Blood AUCinf for Total Radioactivity to Plasma Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Amount Excreted in Urine (Aeu) of Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Amount Excreted in Feces (Aef) of Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
Secondary outcomes:
measure: Metabolite Profile of [14C]-darigabat in Plasma, Urine and Feces
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Identification of [14C]-darigabat Metabolites Found in Plasma, Urine and Feces
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Structural Elucidation of [14C]-darigabat Metabolites ≥10% of the Total [14C]-darigabat Radioactivity Found in Plasma, Urine and Feces
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Day 16
measure: Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Values
timeFrame: Up to Day 15
measure: Number of Participants with Clinically Significant Changes in Vital Signs
timeFrame: Up to Day 15
measure: Number of Participants with Clinically Significant Changes in Laboratory Assessments
timeFrame: Up to Day 15
measure: Number of Participants with Clinically Significant Changes in Physical and Neurological Examination Results
timeFrame: Up to Day 15
Other outcomes:
Locations:
city: Austin
country: United States
facility: Austin, Texas
state: Texas
Study officials:
References: