A Study to Evaluate Pharmacokinetic and Safety Trial of Emraclidine in Participants With Renal Impairment Compared With Participants With Normal Renal Function

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 Renal Impairment Compared With Adult Participants With Normal Renal Function

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

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cerevel Clinical Trial Support; Email: cerevelclinicaltrials@cerevel.com

Study Locations

• United States
  • California
    • Tustin, California, United States, 92780
      • Recruiting
      • Tustin, California
      • Contact: Katia Medina; Phone Number: 714-550-9990; Email: Katia.Medina@ocresearchcenter.com
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • Miami, Florida
      • Contact: Dyal Garg; Phone Number: 561-704-4213; Email: dgarg8838@aol.com
    • Miami, Florida, United States, 33014
      • Recruiting
      • Miami, Florida
      • Contact: Jesus Oliva; Phone Number: 305-817-2900; Email: joliva@ErgClinical.com
    • Orlando, Florida, United States, 32808
      • Recruiting
      • Orlando, Florida
      • Contact: Danielle M. Cortese; Phone Number: 407-988-1075; Email: dcortese@omegarcllc.com
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • Knoxville, Tennessee
      • Contact: Suzann Cloninger; Phone Number: 865-305-9100; Email: suzann.cloninger@amrllc.com

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. For All 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]).
   • 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 investigational medicinal product (IMP).

2. Additional Criteria for Participants With Normal Renal Function

   • Age that is within ±10 years of the median age for the renal impairment groups.
   • Body weight that is within ±15% of the median body weight for the renal impairment groups.
   • 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.
   • Normal renal function: Estimated glomerular filtration rate (eGFR) ≥90 milliliter per minute (mL/min) determined using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Renal function assessed at Baseline (Check-in/Day -1) should not deviate more than 30% from the Screening value.

3. Additional Criteria for Participants With Renal Impairment

   • Mild, moderate, or severe renal impairment based on eGFR determined using the 2021 CKD-EPI equation. Renal function assessed at Baseline (Check-in/Day -1) should not deviate more than 30% from the Screening value.
   • Stable disease, defined as no clinically significant changes in disease status as documented by most recent eGFR assessment (within at least 3 months before Screening).
   • Stable concomitant medications for the management of individual participant's medical history; on a case-by-case basis, with input from the sponsor, participants receiving fluctuating concomitant medication/treatment may be considered if the underlying disease is under control.

Key Exclusion Criteria:

1. For All Participants

   • "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) Any "yes" response on Suicidal Ideation Item 1 or Item 2 that was within the individual's lifetime but not within the past 12 months should be discussed with the medical monitor prior to inclusion of the participant in the trial.
   • Serious risk of suicide in the opinion of the investigator is also exclusionary.
   • History of moderate to severe substance or alcohol-use disorder (excluding nicotine or caffeine) as per DSM-5 criteria within 12 months prior to signing the informed consent form (ICF).
   • Receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or booster within 7 days of planned dosing.

   In addition, participants who plan to receive SARS-CoV-2 vaccination or booster while participating in the trial or for a minimum of 7 days (to cover at least 5 half-lives of IMP) after the last dose of investigational medicinal product (IMP) will be excluded.

   - Have recently been diagnosed with symptomatic coronavirus disease-2019 (COVID-19) or test positive (i.e., using polymerase chain reaction [PCR] or rapid antigen test) for SARS-CoV-2 within 15 days prior to signing the ICF.

2. Additional Criteria for Participants With Normal Renal Function

   - Current or past history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, genitourinary, endocrine (including diabetes mellitus), malignancy (except for surgically excised non-melanomatous skin cancers or in situ cervical cancer, at the discretion of the investigator), 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.

3. Additional Criteria for Participants With Renal Impairment

   • Evidence of disease that is not explained by current/known medical history, i.e., organ dysfunction (including malignancies) or any clinically significant deviation from normal in physical examination, vital signs, ECG, or clinical laboratory determinations beyond what is consistent with renal impairment and other underlying conditions.
   • Participants who have received an organ transplant or are currently waiting for an organ transplant and are listed on the national transplant list.
   • Participants who require dialysis
   • Participants with nephrotic syndrome.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

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: Mild Renal Impairment; Participants will receive a single oral dose of 10 milligrams (mg) emraclidine on Day 1.	Drug: Emraclidine; Oral tablets; Other Names: CVL-231
Experimental: Moderate Renal Impairment; Participants will receive a single oral dose of 10 mg emraclidine on Day 1.	Drug: Emraclidine; Oral tablets; Other Names: CVL-231
Experimental: Severe Renal Impairment; Participants will receive a single oral dose of 10 mg emraclidine on Day 1.	Drug: Emraclidine; Oral tablets; Other Names: CVL-231
Experimental: Normal Renal Function; Participants will receive a single oral dose of 10 mg emraclidine on Day 1.	Drug: Emraclidine; Oral tablets; 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 5
Maximum Observed Unbound Plasma Concentration (Cmax,u) of Emraclidine	Pre-dose and at multiple timepoints post-dose up to Day 5
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 5
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 5
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 5
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 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Treatment Emergent Adverse Events (TEAEs)		Up to Day 15
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Values		Up to Day 5
Number of Participants With Clinically Significant Changes in Vital Signs		Up to Day 5
Number of Participants With Clinically Significant Change in Laboratory Assessments		Up to Day 5
Number of Participants With Clinically Significant Change in Physical and Neurological Examination Results		Up to Day 5
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.	Up to Day 5

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC
• Investigators: Study Director: Erica Koenig, Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2023
• Primary Completion (Estimated): January 15, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: July 2, 2023
• First Submitted That Met QC Criteria: July 2, 2023
• First Posted (Actual): July 11, 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: Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency
• Other Study ID Numbers: CVL-231-SP-1007

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