Clinical trial NCT05245539: Trial to Study the Effect of CVL-231 on 24-Hour Ambulatory Blood Pressure in Participants With Schizophrenia
Official title: A Randomized, Double-Blind Trial to Study the Effect of CVL-231 on 24-Hour Ambulatory Blood Pressure in Participants With Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Blood Pressure
Schizophrenia
Lead sponsor: Cerevel Therapeutics, LLC
Sponsor class: INDUSTRY
First posted: 2022-02-18
Enrollment: 151
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Mean change from Baseline to Week 8 in the 24-hour ambulatory SBP (Systolic Blood Pressure)
timeFrame: Baseline to week 8
Secondary outcomes:
measure: Mean changes from Baseline to Weeks 4 and 8 in ambulatory SBP during daytime period
timeFrame: At weeks 4 and 8
measure: Mean changes from Baseline to Weeks 4 and 8 in ambulatory SBP during nighttime period
timeFrame: At weeks 4 and 8
measure: Mean change from Baseline to Week 4 in the 24-hour ambulatory SBP
timeFrame: At week 4
measure: Mean change from Baseline to Weeks 4 and 8 in the 24-hour ambulatory DBP (Diastolic blood pressure)
timeFrame: At week 8
measure: Mean change from Baseline to Weeks 4 and 8 in the 24-hour ambulatory HR (Heart rate)
timeFrame: At weeks 4 and 8
measure: Number of treatment-emergent adverse events
timeFrame: Screening through day 84
measure: Frequency of clinically significant changes in electrocardiograms
timeFrame: Baseline through day 84
measure: Frequency of clinically significant changes in clinical laboratory assessments
timeFrame: Baseline through day 84
measure: Frequency of clinically significant changes in vital sign measurements
timeFrame: Baseline through day 84
measure: Frequency of clinically significant changes in physical examination results
timeFrame: Baseline through day 84
measure: Frequency of clinically significant changes in neurological examination results
timeFrame: Baseline through day 84
measure: Frequency of clinically significant findings in suicidality assessed using the C-SSRS (Columbia Suicide Severity Rating Scale)
timeFrame: Baseline through day 84
measure: Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the SAS (Simpson Angus Scale)
timeFrame: Baseline through day 84
measure: Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the AIMS (Abnormal Involuntary Movement Scale)
timeFrame: Baseline through day 84
measure: Frequency of clinically significant findings in extrapyramidal symptoms evaluated using the BARS (Barnes Akathisia Rating Scale)
timeFrame: Baseline through day 84
measure: Steady state CVL-231 Peak Plasma Concentration (Cmax) for CVL-231 and Metabolite (PF-06892787)
timeFrame: Baseline through day 84
measure: Area under the plasma concentration-time curve over dosing interval (AUCτ) for CVL-231 and Metabolite (PF-06892787)
timeFrame: Baseline through day 84
Other outcomes:
Locations:
city: Bentonville
country: United States
facility: Pillar Clinical Research LLC
state: Arkansas
city: Little Rock
country: United States
facility: Woodland International Research Group LLC - ERG - PPDS
state: Arkansas
city: Long Beach
country: United States
facility: Collaborative NeuroScience Research, LLC - Torrance - Apex - PPDS
state: California
city: Miami
country: United States
facility: Innovative Clinical Research, Inc - ClinEdge - PPDS
state: Florida
city: Chicago
country: United States
facility: Uptown Research Institute LLC
state: Illinois
city: Lincolnwood
country: United States
facility: Pillar Clinical Research LLC
state: Illinois
city: Marlton
country: United States
facility: Hassman Research Institute - Apex - PPDS
state: New Jersey
city: North Canton
country: United States
facility: Neuro-Behavioral Clinical Research, Inc.
state: Ohio
city: Austin
country: United States
facility: Community Clinical Research
state: Texas
city: Richardson
country: United States
facility: Pillar Clinical Research LLC
state: Texas
Study officials:
affiliation: Cerevel Therapeutics, LLC
name: Erica Koenig, PhD
role: STUDY_DIRECTOR
References: