Decentrialz logo
  • HIPAA Compliant
  • ISO 27001 Certified
Find Trials
About UsContact
Become a Volunteer+1 877 705 1914

Status:

COMPLETED

A Multiple Ascending Dose Trial of CVL-231 in Subjects With Schizophrenia

Lead Sponsor:

Cerevel Therapeutics, LLC

Conditions:

Schizophrenia

Eligibility:

All Genders

18-55 years

Phase:

PHASE1

Brief Summary

The aim of this trial is to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CVL-231 following multiple-dose oral administration in subjects with schizophrenia...

Eligibility Criteria

Inclusion

  • Subjects with a primary diagnosis of schizophrenia per DSM-5, as confirmed by the MINI.
  • Subjects with the following scores on the PANSS at time of signing ICF and at Day -1: • Positive Subscale 7 (hostility) ≤3 (normal to moderate) • General Psychopathology Subscale 8 (uncooperativeness) ≤3 (normal to moderate)
  • Subjects with the following scores (normal to mild symptoms) at time of signing ICF and at Day -1: • All individual items of the Modified SAS (M-SAS) \<2 • All individual items (Items 1-7) of the Abnormal Involuntary Movement Scale (AIMS) \<2 • Clinical global assessment item of the Barnes Akathisia Rating Scale (BARS) \<3
  • Body mass index of 17.5 to 38.0 kg/m2 and a total body weight \>50 kg (110 lbs).
  • Cohorts 1 Through 5 (Part A):
  • Subjects are eligible to be included in trial (Cohorts 1 through 5) only if all of the following additional criteria apply:
  • Male and female subjects, ages 18 to 50 years, inclusive.
  • Subjects with a score on the CGI-S ≤4 (normal to moderately ill) at time of signing ICF and at Day -1.
  • Subjects with a PANSS total score of ≤80 at the time of signing ICF and at Day -1.
  • Cohort 6 (Part B):
  • Subjects are eligible to be included in trial (Cohort 6) only if all of the following additional criteria apply:
  • Male and female subjects, ages 18 to 55 years, inclusive.
  • Subjects with a score on the CGI-S ≥4 (moderately to severely ill) at time of signing ICF and at Day -1.
  • Subjects with a PANSS total score of ≥80 at the time of signing ICF and at Day -1. Additionally, subjects must meet a score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale items at the time of signing ICF and at Day -1:
  • Positive Scale 1 (delusions)
  • Positive Scale 2 (conceptual disorganization)
  • Positive Scale 3 (hallucinatory behavior)
  • Positive Scale 6 (suspiciousness/persecution)
  • Subjects with a history of relapse and/or exacerbation of symptoms when not receiving antipsychotic treatment, excluding the current episode.
  • Subjects must be experiencing an acute exacerbation or relapse of symptoms, with onset less than 2 months prior to signing ICF.

Exclusion

  • Subjects with a current DSM-5 diagnosis other than schizophrenia including, but not limited to, mental retardation; schizoaffective disorder; schizophreniform disorder; psychotic depression; major depressive disorder; bipolar disorder; post-traumatic stress disorder; generalized anxiety disorder, obsessive compulsive disorder, eating disorders (bulimia, anorexia), or other anxiety disorders as a primary diagnosis (subjects with anxiety symptoms secondary to schizophrenia are allowed); delirium, dementia, amnestic, or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
  • Subjects with schizophrenia who were considered resistant/refractory to antipsychotic treatment by history or who had a history of failure to respond to clozapine or response to clozapine treatment only.
  • Subjects with EPS being treated with a medication that required dose modification and/or new treatment within 6 months prior to signing ICF.
  • Subjects with a current history of significant pulmonary, gastrointestinal, renal, hepatic, metabolic, endocrine (including newly diagnosed diabetes mellitus or subjects with known diabetes mellitus with glycosylated hemoglobin (HbA1c)\>7.5%), hematological, immunological, psychiatric (excluding schizophrenia), or neurological disease.
  • Subjects with a current or past history of significant cardiovascular disease.
  • Subjects who experienced acute depressive symptoms within the past 30 days.
  • Subjects with epilepsy or a history of seizures, except for a single seizure episode, eg, a childhood febrile seizure, or a seizure related to trauma or alcohol withdrawal.
  • An active central nervous system infection, demyelinating disease, degenerative neurological disease, mental retardation, or any central nervous system disease deemed to be progressive.
  • 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 ICF.
  • Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent).
  • Human immunodeficiency virus seropositive status or acquired immunodeficiency syndrome, chronic hepatitis B or C.
  • Subject with a positive urine drug screen for illicit drugs or a positive breathalyzer test for alcohol.
  • Subjects with medically significant abnormal laboratory test results, vital sign results, or ECG findings.
  • Subjects who received transcranial magnetic stimulation or electroconvulsive therapy within 60 days of screening.
  • Any condition possibly affecting drug absorption, including bowel resections, bariatric weight loss surgery, or gastrectomy (this does not include gastric banding).
  • Subjects with difficulty swallowing.
  • Subjects with a history of neuroleptic malignant syndrome.
  • Subject who refuses to abstain from grapefruit-containing foods or beverages, or Seville orange-containing foods or beverages.
  • Cohorts 1 Through 5 (Part A) Subjects are excluded from the trial (Cohorts 1 through 5) if any of the following additional criteria apply:
  • Subjects who have experienced psychosis requiring hospitalization within the 6 months prior to signing ICF.
  • Subjects who experienced psychosis requiring a change in their antipsychotic medication (either drug type or dose) within the 3 months prior to signing ICF.
  • Subjects who fulfill any of the following dietary restrictions: • History of chronic consumption of \>400 mg/day of caffeine-containing drinks or food • Refuses to abstain from caffeine-containing foods or caffeinated beverages for 48 hours prior to Day -1 through Follow up Visit • Refuses to abstain from alcohol from 7 days prior to Day -1 through Follow-up Visit
  • Subjects who have participated in any clinical trial within 60 days prior to signing ICF.
  • Subjects with a 12-lead ECG demonstrating any of the following:
  • Abnormal ST-T-wave morphologies that may interfere with QT analysis, such as flat or poorly defined end of the T wave or prominent U waves
  • Left ventricular hypertrophy
  • QT interval corrected for heart rate QTcF \>450 msec
  • QRS interval \>110 msec
  • Left or right bundle branch block
  • PR interval \>240 msec
  • Heart rate \<50 bpm or \>90 bpm
  • Second- or third-degree atrioventricular block
  • Systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg at Screening or Day -1, will be taken with subjects in the supine/semi-recumbent position, or symptomatic hypotension, or orthostatic hypotension, which is defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the immediately previous supine blood pressure. Subjects who are receiving chronic treatment with antihypertensive medications at Screening are also excluded.
  • Cohort 6 (Part B) Only Subjects are excluded from trial (Cohort 6 only) if any of the following additional criteria apply:
  • Subjects who have been hospitalized \>14 days for the current episode of schizophrenia at the time of signing the ICF, excluding hospitalization for psychosocial reasons.
  • Subjects presenting with a first episode of schizophrenia, based on clinical judgment of the investigator.
  • Subjects with a 12-lead ECG exclusion as in Part A but will allow right bundle branch block in Part B.
  • Systolic blood pressure \>130 mmHg and/or diastolic blood pressure \>80 mmHg at Screening or Day -1 and subjects with orthostatic hypotension, defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the average resting supine/semi-recumbent blood pressure at Screening or Day -1, will be excluded. Subjects with a heart rate \<50 bpm or \>90 bpm. Subjects who are receiving chronic treatment with antihypertensive medications at Screening are also excluded.

Key Trial Info

Start Date :

October 15 2019

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

June 3 2021

Estimated Enrollment :

130 Patients enrolled

Trial Details

Trial ID

NCT04136873

Start Date

October 15 2019

End Date

June 3 2021

Last Update

July 2 2021

Active Locations (5)

Enter a location and click search to find clinical trials sorted by distance.

Page 1 of 2 (5 locations)

1

Pillar Clinical Research

Bentonville, Arkansas, United States, 72712

2

Woodlands International Research Group

Little Rock, Arkansas, United States, 72211

3

Synergy San Diego

Lemon Grove, California, United States, 91945

4

Collaborative Neuroscience Network, LLC

Long Beach, California, United States, 90806