Clinical trial NCT06301971: A Study to Assess Mass Balance, Pharmacokinetics, Metabolism, and Excretion of Emraclidine in Healthy Adult Male Participants
Official title: A Phase 1, Open-Label Trial to Assess the Mass Balance, Pharmacokinetics, Metabolism, and Excretion of Emraclidine 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: 2024-03-08
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 study is to determine the mass balance, routes, and rates of elimination of total radioactivity and characterize the pharmacokinetics (PK) of emraclidine, metabolite CV-0000364, and total radioactivity in plasma and whole blood following a single oral dose of \[14C\]-emraclidine in healthy adult male participants.


Eligibility criteria: Inclusion Criteria:

1. Body mass index (BMI) of 18.5 to 35.0 kilograms per square meters (kg/m\^2), inclusive, and a total body weight ≥50 kg \[110 Pounds (lbs)\].
2. A male participant who is sexually active with a pregnant or a nonpregnant woman of childbearing potential must agree to use a condom during the trial and for 90 days after the dose of investigational medicinal product (IMP). In addition, male participants should not donate sperm for a minimum of 90 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.
4. Capable of consuming the standard diet.
5. History of a minimum of 1 bowel movement per day.

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 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. Use of any prescription and over-the-counter medications from 28 days prior to first dose of IMP or likely to require concomitant therapy. Vaccinations or boosters within 28 days of planned dosing or while on trial.
5. Positive result for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis B total core antibody, or hepatitis C antibody with detectable viral ribonucleic acid (RNA) levels at Screening.
6. Positive drug screen (including cotinine and tetrahydrocannabinol \[THC\]) or a positive test for alcohol.
7. Any of the following clinical laboratory test results at the Screening Visit or Check-in (Day -1), which can be confirmed by a single repeat measurement, if deemed necessary:

   * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2× upper limit of normal (ULN).
   * Total bilirubin ≥1.5×ULN. If Gilbert's syndrome is suspected, total bilirubin ≥1.5×ULN is acceptable if the conjugated or direct bilirubin fraction is \<20% of total bilirubin.
8. 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 Zero to Infinity (AUCinf) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: AUC from Time 0 to last Quantifiable Concentration (AUClast) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Maximum Plasma Concentration (Cmax) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Time to Last Measurable Concentration (Tlast) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Time to Maximum Observed Concentration (Tmax) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Apparent Terminal Elimination Half-life (t½) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Terminal Rate Constant (λz) of Emraclidine, its Metabolite CV-0000364 and Total Radioactivity in Plasma and Whole Blood
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Total Plasma Clearance After Oral Administration (CL/F) of Emraclidine
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 Emraclidine
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Ratio of Plasma AUCinf for Emraclidine to Plasma AUCinf for Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Ratio of Plasma AUCinf for Metabolite CV-0000364 to Plasma AUCinf for Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Ratio of Plasma AUCinf for Metabolite CV-0000364 to Plasma AUCinf for Emraclidine
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 AUCinf for 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: Cumulative Aeu of Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Percentage Excreted in Urine (feu) of Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Cumulative feu 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
measure: Cumulative Aef of Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Percentage Excreted in Feces (fef) of Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Cumulative fef of Total Radioactivity
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Percentage Dose (%Dose) of Total Radioactivity Excreted in Urine Plus Feces Combined
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Cumulative Percentage Dose of Total Radioactivity Excreted in Urine Plus Feces Combined
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
Secondary outcomes:
measure: Metabolite Profile of Emraclidine in Plasma, Urine and Feces
timeFrame: Pre-dose and at multiple time points post-dose up to Day 15
measure: Structural Identification of Emraclidine Metabolites 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 Treatment Emergent Adverse Events (TEAEs)
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
measure: Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Score
timeFrame: Up to Day 15
Other outcomes:
Locations:
city: Austin
country: United States
facility: Austin, Texas
state: Texas
Study officials:
References: