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

A Phase 1, Open-label Trial to Evaluate the Pharmacokinetics and Safety Following a Single Dose of Emraclidine in Adult Participants With Mild, Moderate, and Severe Hepatic Impairment Compared With Adult Participants With Normal Hepatic Function

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Emraclidine

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: María Inés Enei; Phone Number: +54 911 652 128 10; Email: Ines.Enei@ppd.com

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Miami, Florida
    • Orlando, Florida, United States, 32809
      • Recruiting
      • Orlando, Florida
  • Texas
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • San Antonio, Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Severe Hepatic Impairment; Participants will receive a single oral dose of 10 milligrams (mg) emraclidine.	Drug: Emraclidine; Tablet; Other Names: CVL-231
Experimental: Moderate Hepatic Impairment; Participants will receive a single oral dose of 10 mg emraclidine.	Drug: Emraclidine; Tablet; Other Names: CVL-231
Experimental: Mild Hepatic Impairment; Participants will receive a single oral dose of 10 mg emraclidine.	Drug: Emraclidine; Tablet; Other Names: CVL-231
Experimental: Normal Hepatic Function; Participants will receive a single oral dose of 10 mg emraclidine.	Drug: Emraclidine; Tablet; Other Names: CVL-231

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Emraclidine	Pre-dose and at multiple timepoints post-dose up to Day 7
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Emraclidine	Pre-dose and at multiple timepoints post-dose up to Day 7
Area Under the Plasma Concentration-time Curve from Time Zero to t (AUC0-t) of Emraclidine	Pre-dose and at multiple timepoints post-dose up to Day 7
Area Under the Unbound Plasma Concentration-time Curve from Time Zero to t (AUC0-t,u) of Emraclidine	Pre-dose and at multiple timepoints post-dose up to Day 7
Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUCinf) of Emraclidine	Pre-dose and at multiple timepoints post-dose up to Day 7
Area Under the Unbound Plasma Concentration-time Curve From Time Zero to Infinity (AUCinf,u) of Emraclidine	Pre-dose and at multiple timepoints post-dose up to Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)		Day 1 up to Follow-up (Day 15)
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values		Days 1 to 7
Number of Participants With Clinically Significant Changes in Vital Signs		Days 1 to 7
Number of Participants With Clinically Significant Changes in Laboratory Assessments		Days 1 to 7
Number of Participants With Clinically Significant Changes in Physical and Neurological Examination Results		Days 1 to 7
Changes in Columbia Suicide Severity Rating Scale (C-SSRS) Score	The C-SSRS includes 'yes' or 'no' responses for assessment of suicidal ideation and behavior as well as numeric ratings for 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.	Days 1 to 7

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2023
• Primary Completion (Estimated): December 15, 2024
• Study Completion (Estimated): December 23, 2024

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: June 29, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CVL-231-SP-1008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No