Trial to Study the Effect of CVL-231 on 24-Hour Ambulatory Blood Pressure in Participants With Schizophrenia

A Randomized, Double-Blind Trial to Study the Effect of CVL-231 on 24-Hour Ambulatory Blood Pressure in Participants With Schizophrenia

The purpose of this trial is to characterize the effects of 2 oral doses (over 8 weeks total) of CVL-231 on ambulatory blood pressure and heart rate in patients with stable schizophrenia.

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Blood Pressure
• Intervention / Treatment: Drug: CVL-231

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Bentonville, Arkansas, United States, 72712
      • Pillar Clinical Research LLC
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group LLC - ERG - PPDS
  • California
    • Long Beach, California, United States, 90806
      • Collaborative NeuroScience Research, LLC - Torrance - Apex - PPDS
  • Florida
    • Miami, Florida, United States, 33016
      • Innovative Clinical Research, Inc - ClinEdge - PPDS
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Uptown Research Institute LLC
    • Lincolnwood, Illinois, United States, 60712
      • Pillar Clinical Research LLC
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute - Apex - PPDS
  • Ohio
    • North Canton, Ohio, United States, 44720
      • Neuro-Behavioral Clinical Research, Inc.
  • Texas
    • Austin, Texas, United States, 78754
      • Community Clinical Research
    • Richardson, Texas, United States, 75080
      • Pillar Clinical Research LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female participants, ages 30 to 60 years, inclusive, at the time of signing the ICF.
• Primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI version 7.0.2.
• PANSS Total Score ≤70 at the time of signing the ICF and Check-in (Day -5).

Exclusion Criteria:

• Current DSM-5 diagnosis other than schizophrenia including, but not limited to, mental retardation; schizoaffective disorder; major depressive disorder; schizophreniform disorder; psychotic depression; bipolar disorder; post-traumatic stress disorder; generalized anxiety disorder, obsessive compulsive disorder, eating disorders (bulimia, anorexia), or other anxiety disorders as a primary diagnosis (Note: Anxiety symptoms secondary to schizophrenia are allowed); delirium, dementia, amnestic, or other cognitive disorders. Acute depressive symptoms within 30 days prior to signing the ICF that require treatment with an antidepressant are exclusory. Additional excluded conditions include borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.

• Any of the following:

  • Schizophrenia considered resistant/refractory (defined as failure to respond to 2 or more courses of adequate pharmacological treatment) to antipsychotic treatment by history
  • History of failure to respond to clozapine
  • Response to clozapine treatment only
• History of extrapyramidal symptoms treated with a medication that required dose modification and/or new treatment within 6 months prior to signing the ICF.
• Current or past history of significant cardiovascular disease including any of the following: ischemic heart disease, myocardial infarction, cardiac valvulopathy, cardiac surgery revascularization (coronary artery bypass grafting) or stenting or percutaneous transluminal coronary angioplasty), hypertension, receiving medications to treat hypertension, orthostatic hypotension, angina, unstable angina, cerebrovascular accident or stroke or transient ischemic attack, pacemaker, atrial fibrillation, atrial flutter, paroxysmal atrial tachycardia, or non-sustained or sustained ventricular tachycardia, pulmonary arterial hypertension, sick sinus syndrome, Type 2 second-degree or third-degree atrioventricular block, congestive heart failure, personal or family history of sudden death or long QT syndrome, unexplained syncope or syncope within the last 3 years regardless of etiology.

• 12-lead ECG demonstrating any of the following at the Screening Visit or at Check-in (Day -5):

  • QTcF interval >450 ms
  • QRS interval >120 ms (unless right bundle branch block)
  • PR interval >200 ms
  • 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 bpm or >90 bpm
  • Abnormal acute ECG changes (such as clinically significant ST depression or elevation or T wave inversion)
  • Abnormal heart rhythm (atrial fibrillation and atrial flutter)

• Blood pressure measurements demonstrating any of the following at the Screening Visit and at Check-in (Day -5):

  • Systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg

    o Blood pressure will be measured in a seated position after at least 3 minutes of rest. The average of 3 measurements will be used to determine eligibility.

  • Orthostatic hypotension, defined as a decrease of ≥20 mmHg in systolic blood pressure after at least 2 minutes of standing compared with the average of the resting supine blood pressure measurement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CVL-231 Dose Level 1; 10 mg once daily	Drug: CVL-231; CVL-231 is a brain penetrant mAChR activator that selectively binds to the M4 mAChR subtype while sparing other muscarinic receptor subtypes (M1, M2, M3, and M5). CVL-231 is being developed for treatment of psychosis in schizophrenia.
Experimental: CVL-231 Dose Level 2; 30 mg once daily	Drug: CVL-231; CVL-231 is a brain penetrant mAChR activator that selectively binds to the M4 mAChR subtype while sparing other muscarinic receptor subtypes (M1, M2, M3, and M5). CVL-231 is being developed for treatment of psychosis in schizophrenia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean change from Baseline to Week 8 in the 24-hour ambulatory SBP (Systolic Blood Pressure)	Baseline to week 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Mean changes from Baseline to Weeks 4 and 8 in ambulatory SBP during daytime period	At weeks 4 and 8
Mean changes from Baseline to Weeks 4 and 8 in ambulatory SBP during nighttime period	At weeks 4 and 8
Mean change from Baseline to Week 4 in the 24-hour ambulatory SBP	At week 4
Mean change from Baseline to Weeks 4 and 8 in the 24-hour ambulatory DBP (Diastolic blood pressure)	At week 8
Mean change from Baseline to Weeks 4 and 8 in the 24-hour ambulatory HR (Heart rate)	At weeks 4 and 8
Number of treatment-emergent adverse events	Screening through day 84
Frequency of clinically significant changes in electrocardiograms	Baseline through day 84
Frequency of clinically significant changes in clinical laboratory assessments	Baseline through day 84
Frequency of clinically significant changes in vital sign measurements	Baseline through day 84
Frequency of clinically significant changes in physical examination results	Baseline through day 84
Frequency of clinically significant changes in neurological examination results	Baseline through day 84
Frequency of clinically significant findings in suicidality assessed using the C-SSRS (Columbia Suicide Severity Rating Scale)	Baseline through day 84
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the SAS (Simpson Angus Scale)	Baseline through day 84
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the AIMS (Abnormal Involuntary Movement Scale)	Baseline through day 84
Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the BARS (Barnes Akathisia Rating Scale)	Baseline through day 84
Steady state CVL-231 Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (PF-06892787)	Baseline through day 84
Area under the plasma concentration-time curve over dosing interval (AUCτ) for CVL-231 and Metabolite (PF-06892787)	Baseline through day 84

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Actual): October 19, 2022
• Study Completion (Actual): November 14, 2022

Study Registration Dates

• First Submitted: January 27, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 13, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia
• Other Study ID Numbers: CVL-231-1005

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
• product manufactured in and exported from the U.S.: No