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A Trial to Evaluate the Effects of Itraconazole and Carbamazepine on the Pharmacokinetics of Emraclidine and of Emraclidine on the Pharmacokinetics of Metformin in Healthy Adult Participants

Sponsored by Cerevel Therapeutics, LLC

About this trial

Last updated 2 years ago

Study ID

CVL-231-HV-1010

Status

Recruiting

Type

Interventional

Phase

Phase 1

Placebo

No

Accepting

18-75 Years
18 to 55 Years
All
All

Trial Timing

Ended 2 years ago

What is this trial about?

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.

What are the Participation Requirements?

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.

Exclusion Criteria for Part A:

- History of presence of any of the following and deemed clinically significant by the
investigator or designee and confirmed by the medical monitor:

- Ventricular dysfunction or risk factors for torsades de pointes (e.g., heart
failure, cardiomyopathy, family history of long-QT syndrome)

- 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) > upper limit
of normal (ULN).

- Total bilirubin >ULN. If Gilbert's syndrome is suspected, total bilirubin >ULN is
acceptable if the conjugated or direct bilirubin fraction is <20% of total
bilirubin.

- Hypokalemia (potassium levels < lower limit of normal [LLN] millimoles per liter
[mmol/L]), and/or hypomagnesemia (magnesium levels <1.2 milligrams per deciliter
[mg/dL]; <0.5 mmol/L), and/or hypocalcemia (corrected serum calcium <8.0 mg/dL or
ionized calcium <1.0 mmol/L).

Exclusion Criteria for Part B:

- Participants positive for human leukocyte antigen (HLA)-B*1502 or HLA-A*3101.

- Family history of drug reaction with eosinophilia and systemic symptoms (DRESS).

- Family history of porphyria.

- History of cardiac conduction disturbance including second- and third-degree
atrioventricular heart block.

- 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:

- Platelets, white blood cell count, absolute neutrophil count, or hemoglobin <LLN.

- Serum sodium <LLN.

- 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:

- AST or ALT >ULN.

- Total bilirubin >ULN. If Gilbert's syndrome is suspected, total bilirubin >ULN is
acceptable if the conjugated or direct bilirubin fraction is <20% of total
bilirubin.

Exclusion Criteria for Part C:

- Any of the following clinical laboratory test results at the Screening Visit or
Check-in (Day -1), as assessed by the central laboratory and confirmed by a single
repeat measurement, if deemed necessary:

- AST or ALT ≥2 × 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.

- Female participants who are pregnant, breastfeeding, or planning to become pregnant
during IMP treatment or within 7 days after the last dose of IMP. Women of
childbearing potential must have a negative serum pregnancy test result at the
Screening Visit and a negative urine pregnancy test result at Check-in.

[Note: Other inclusion and exclusion criteria as per protocol may apply.]

Locations

Location

Status

Recruiting