Healthy Volunteers
Conditions
Brief summary
The primary purpose of the study is to evaluate the effect of itraconazole, a strong cytochrome P450 (CYP) 3A4 inhibitor, on the pharmacokinetics (PK) of emraclidine and metabolite CV-0000364 in Part A, the effect of carbamazepine, a strong CYP3A4 inducer, on the PK of emraclidine and metabolite CV-0000364 in Part B, and to evaluate the effect of emraclidine on the PK of metformin in Part C in healthy adult participants.
Interventions
DRUGCarbamazepine
Carbamazepine tablets.
DRUGMetformin
Metformin tablets.
DRUGItraconazole
Itraconazole oral solution.
DRUGEmraclidine
Emraclidine tablets.
Sponsors
Cerevel Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
for All Participants: * Healthy as determined by medical evaluation, including medical and psychiatric history, physical and neurological examinations, ECG, vital sign measurements, and laboratory test results, as evaluated by the investigator. * Body mass index of 18.5 to 35.0 kilograms per square meter (kg/m\^2), inclusive, and a total body weight ≥50 kilograms (kg) (110 pounds \[lbs\]). Inclusion Criteria for Part A: * Male and female (women of nonchildbearing potential only) participants, ages 18 to 55 years, inclusive, at the time of signing the informed consent form (ICF). Inclusion Criteria for Part B: * Male and female (women of nonchildbearing potential only) participants, ages 18 to 55 years, inclusive, at the time of signing the ICF. Inclusion Criteria for Part C: * Male and female (both women of childbearing and nonchildbearing potential) participants, ages 18 to 55 years, inclusive, at the time of signing the ICF. * Sexually active women of childbearing potential must agree to use at least an acceptable birth control method during the trial and for 7 days after the last dose of IMP. Acceptable birth control methods that result in a failure rate of more than 1% per year include the following: * Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action * Male or female condom with or without spermicide * Cap, diaphragm, or sponge with spermicide
Exclusion criteria
for All Participants: * 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. * 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, or Preparatory Acts/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. * 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. * 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. * Positive drug screen (including cotinine and tetrahydrocannabinol \[THC\]) or a positive test for alcohol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part C: AUCinf of Metformin | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 11 in TP 2 of Part C |
| Part C: Cmax of Metformin | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 11 in TP 2 of Part C |
| Part A: Area Under the Plasma Concentration-time Curve from Time Zero to Last Specified Sampling Time (AUC0-t) of Emraclidine and its Metabolite CV-0000364 | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 15 in TP 2 of Part A |
| Part B: AUC0-t of Emraclidine and its Metabolite CV-0000364 | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 20 in TP 2 of Part B |
| Part C: AUC0-t of Metformin | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 11 in TP 2 of Part C |
| Part A: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Emraclidine and its Metabolite CV-0000364 | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 15 in TP 2 of Part A |
| Part B: AUCinf of Emraclidine and its Metabolite CV-0000364 | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 20 in TP 2 of Part B |
| Part A: Maximum Observed Plasma Concentration (Cmax) of Emraclidine and its Metabolite CV-0000364 | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 15 in TP 2 of Part A |
| Part B: Cmax of Emraclidine and its Metabolite CV-0000364 | Pre-dose and at multiple time points post-dose from Day 1 in TP 1 up to Day 20 in TP 2 of Part B |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values | Up to end of treatment in each part of the study (up to an average of 15 days) | — |
| Number of Participants With Clinically Significant Changes in Vital Sign Measurements | Up to end of treatment in each part of the study (up to an average of 15 days) | — |
| Number of Participants With Clinically Significant Changes in Laboratory Assessments | Up to end of treatment in each part of the study (up to an average of 15 days) | — |
| Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results | Up to end of treatment in each part of the study (up to an average of 15 days) | — |
| Changes in Suicidality Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score | Up to end of treatment in each part of the study (up to an average of 15 days) | The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). Greater lethality or potential lethality of suicidal behaviors (endorsed on the behavior subscale) indicates increased risk. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Based on Severity | From the first dose up to 1 month following last dose with investigational medicinal product (IMP) in each part of the study | — |
Countries
United States
Outcome results
None listed