A Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of Emraclidine

Cerevel Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Hepatic Impairment

Treatments: Drug: Emraclidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05935033

CVL-231-SP-1008

Details and patient eligibility

About

The primary purpose of this study is to assess the effect of hepatic impairment on the pharmacokinetics (PK) of emraclidine following administration of a single oral dose in participants with mild, moderate, and severe hepatic impairment relative to matched participants with normal hepatic function.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. All Participants

   • Male and female participants, body mass index of ≥18.0 to 42.0 kilograms per meter square (kg/m^2), inclusive, and a total body weight ≥50 kilograms (kg) (110 pounds [lbs]).

2. Additional Inclusion Criteria for Participants With Normal Hepatic Function

   • Participants who are healthy, having no clinically relevant abnormalities. Have normal hepatic function.
   • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and prothrombin time ≤ upper limit of normal (ULN) and albumin ≥ lower limit of normal (LLN) and ≤ ULN. Participants with a history of Gilbert syndrome are eligible provided direct bilirubin fraction is <20% of total bilirubin, and hemoglobin, and reticulocyte counts are all ≤ ULN.

3. Additional Inclusion Criteria for Participants With Hepatic Impairment - Participants with stable hepatic impairment that meets the criteria for Class A, Class B, or Class C of the modified Child-Pugh Classification. Stable hepatic disease defined as no clinically significant change in disease status in the last 28 days prior to the screening visit.

Key Exclusion Criteria:

1. For All Participants

   • 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.

   • Receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or booster within 7 days of planned dosing.

   • Have recently been diagnosed with symptomatic coronavirus disease 2019 (COVID-19) or test positive for SARS-CoV-2 within 15 days prior to signing the informed consent form (ICF).

   • Positive drug screen or a positive test for alcohol at Screening or Baseline (Check-in/Day -1) Visits.

   • Use of prohibited medications prior to randomization or likely to require prohibited concomitant therapy during the trial.

   • Current use of tobacco or nicotine-containing products (cigarettes, cigars, chewing tobacco, snuff, e-cigarettes, etc). Note: Light smokers (<5 cigarettes/day or equivalent) are allowed provided they abstain from the use of tobacco- or nicotine-containing products for at least 2 hours prior to PK assessments.

   • Known allergy or hypersensitivity to the investigational medicinal product (IMP), closely related compounds, or any of their specified ingredients.

   • Has received IMP in a clinical trial of emraclidine within 12 months of signing the ICF.

   • Participants with a 12-lead ECG demonstrating any of the following at the Screening Visit and at Check-in (Day -1):

     • QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 milliseconds (ms)
     • QRS interval >120 ms (unless right bundle branch block)
     • PR interval >200 ms
     • Left ventricular hypertrophy (LVH) with ST depressions and/or T wave inversions in leads with relatively tall R waves (ie, LVH with associated ST-T wave abnormalities)
     • Type 2 second-degree or third-degree atrioventricular block
     • Heart rate <45 beats per minute (bpm) or >100 bpm
     • Abnormal ECG changes (such as clinically significant ST depression or elevation or T wave inversion).
     • Abnormal heart rhythm (such as atrial fibrillation and atrial flutter)

   • Blood pressure measurements demonstrating any of the following at the Screening Visit and/or at Check-in (Day -1):

     • Supine systolic blood pressure ≥140 millimeters of mercury (mmHg) and/or diastolic blood pressure ≥90 mmHg
     • Standing systolic and/or diastolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg
     • Orthostatic hypotension, defined as a decrease of ≥20 mmHg in systolic blood pressure and/or ≥10 mmHg in diastolic blood pressure after at least 2 minutes of standing compared with the average of the resting supine blood pressure measurements.

2. Additional Exclusion Criteria for Participants with Hepatic Impairment

   • Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2 based on the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation at Screening or Check-in (Day -1) visits
   • Acute hepatitis
   • Grade ≥2 hepatic encephalopathy
   • Participants who have received an organ transplant or are currently waiting for an organ transplant and are listed on the national transplant list.
   • Primary biliary cholangitis or primary sclerosing cholangitis
   • ALT or AST >5 × ULN or alkaline phosphatase >2 × ULN. Participants with a history of Gilbert syndrome are eligible provided direct bilirubin fraction is <20% of total bilirubin.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

40 participants in 4 patient groups

Severe Hepatic Impairment

Experimental group

Description:

Participants will receive a single oral dose of 10 milligrams (mg) emraclidine.

Treatment:

Drug: Emraclidine

Moderate Hepatic Impairment

Experimental group

Description:

Participants will receive a single oral dose of 10 mg emraclidine.

Treatment:

Drug: Emraclidine

Mild Hepatic Impairment

Experimental group

Description:

Participants will receive a single oral dose of 10 mg emraclidine.

Treatment:

Drug: Emraclidine

Normal Hepatic Function

Experimental group

Description:

Participants will receive a single oral dose of 10 mg emraclidine.

Treatment:

Drug: Emraclidine