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

NCT ID: NCT05245539

Last Updated: 2022-12-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-24
• Study Completion Date: 2022-11-14

Brief Summary

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.

Conditions

Blood Pressure; Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

CVL-231 Dose Level 1

10 mg once daily

Group Type: EXPERIMENTAL

CVL-231

Intervention Type: DRUG

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.

CVL-231 Dose Level 2

30 mg once daily

Group Type: EXPERIMENTAL

CVL-231

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cerevel Therapeutics, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Erica Koenig, PhD

Role: STUDY_DIRECTOR

Cerevel Therapeutics, LLC

Locations

Pillar Clinical Research LLC

Bentonville, Arkansas, United States

Woodland International Research Group LLC - ERG - PPDS

Little Rock, Arkansas, United States

Collaborative NeuroScience Research, LLC - Torrance - Apex - PPDS

Long Beach, California, United States

Innovative Clinical Research, Inc - ClinEdge - PPDS

Miami, Florida, United States

Uptown Research Institute LLC

Chicago, Illinois, United States

Pillar Clinical Research LLC

Lincolnwood, Illinois, United States

Hassman Research Institute - Apex - PPDS

Marlton, New Jersey, United States

Neuro-Behavioral Clinical Research, Inc.

North Canton, Ohio, United States

Community Clinical Research

Austin, Texas, United States

Pillar Clinical Research LLC

Richardson, Texas, United States

Countries

United States

Other Identifiers

CVL-231-1005

Identifier Type: -

Identifier Source: org_study_id