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A Single Ascending Dose Trial of CVL-936 in Healthy Subjects

Phase 1
Terminated
Conditions
Substance Use Disorders (SUD)
Interventions
Drug: Matching Placebo
Registration Number
NCT04232878
Lead Sponsor
Cerevel Therapeutics, LLC
Brief Summary

The aim of this trial is to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of CVL-936 following single ascending oral doses in healthy subjects.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
10
Inclusion Criteria
  1. Healthy male subjects and female subjects of nonchildbearing potential, ages 18 to 50 years
Exclusion Criteria
  1. Subjects with a current history of significant pulmonary, gastrointestinal, renal, hepatic, metabolic, endocrine, hematological, immunological, psychiatric, or neurological disease that, in the opinion of the investigator or medical monitor, could compromise either subject safety or the results of the trial.
  2. Subjects with epilepsy or a history of seizures
  3. Systolic supine blood pressure ≥130 mmHg and/or supine diastolic blood pressure ≥80 mmHg at Screening or Day -1, or orthostatic hypotension at Screening or Day -1.
  4. Subjects with a history of hypersensitivity to any dopamine-blocker medication.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Active Comparator: Group 1 Period 3:TBD mg CVL-936CVL-936Oral suspension/solution
Placebo Comparator: Group 3: TBD mg Matching PlaceboMatching PlaceboMatching Placebo; Oral suspension/solution
Placebo Comparator: Group 1 Period 1: 0.5mg Matching PlaceboMatching PlaceboMatching Placebo; Oral suspension/solution
Placebo Comparator: Group 1 Period 2:TBD mg Matching PlaceboMatching PlaceboMatching Placebo; Oral suspension/solution
Placebo Comparator: Group 1 Period 3:TBD mg Matching PlaceboMatching PlaceboMatching Placebo; Oral suspension/solution
Active Comparator: Group 2 Period 2:TBD mg CVL-936CVL-936Oral suspension/solution
Active Comparator: Group 2 Period 3:TBD mg CVL-936CVL-936Oral suspension/solution
Placebo Comparator: Group 2 Period 3:TBD mg Matching PlaceboMatching PlaceboMatching Placebo; Oral suspension/solution
Active Comparator: Group 1 Period 1: 0.5mg CVL-936CVL-936Oral suspension/solution
Active Comparator: Group 1 Period 2:TBD mg CVL-936CVL-936Oral suspension/solution
Placebo Comparator: Group 2 Period 1:TBD mg Matching PlaceboMatching PlaceboMatching Placebo; Oral suspension/solution
Active Comparator: Group 3: TBD mg CVL-936CVL-936Oral suspension/solution
Placebo Comparator: Group 2 Period 2:TBD mg Matching PlaceboMatching PlaceboMatching Placebo; Oral suspension/solution
Active Comparator: Group 2 Period 1:TBD mg CVL-936CVL-936Oral suspension/solution
Primary Outcome Measures
NameTimeMethod
Number of Subjects with reported Treatment Emergent Adverse Events (TEAEs)At the end of Period 3 (30 Days)
Number of Subjects with Clinically significant changes in Electrocardiogram measures (PR, RR, QT and QTcF)At the end of Period 3 (30 Days)
Number of Subjects with Clinically meaningful changes in Vital signs (Systolic and Diastolic blood pressures, heart rate, respiratory rate and body temperature)At the end of Period 3 (30 Days)
Change from Baseline of Simpson-Angus Scale (SAS) ResultsAt the end of Period 3 (30 Days)

Evaluating Extrapyramidal symptoms using the SAS. The SAS consists of a list of 10 symptoms of parkinsonism (gait, arm dropping, shoulder shaking, elbow rigidity, wrist rigidity, head rotation, glabella tap, tremor, salivation, and akathisia). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms and a score of 4 representing a severe condition. The SAS total score is the sum of the scores for all 10 items.

Number of Subjects with Clinically significant changes in laboratory measuresAt the end of Period 3 (30 Days)

Number of subjects with clinically significant changes in hematology, serum chemistry and urinalysis will be reported

Change from baseline of the Columbia-Suicide Severity Rating Scale (C-SSRS)At the end of Period 3 (30 Days)

The C-SSRS rates an individual's degree of suicidal ideation (SI) on a scale, ranging from "wish to be dead" to "active suicidal ideation with specific plan and intent." The scale identifies SI severity and intensity, which may be indicative of an individual's intent to commit suicide. C-SSRS SI severity subscale ranges from 0 (no SI) to 5 (active SI with plan and intent).

Change from Baseline of Barnes Akathisia Rating Scale (BARS) ResultsAt the end of Period 3 (30 Days)

Evaluating Extrapyramidal symptoms using the BARS. The BARS consists of 4 items related to akathisia: objective observation of akathisia by the investigator, subjective feelings of restlessness by the subject, subjective distress due to akathisia, and global clinical assessment of akathisia. The first 3 items are rated on a 4-point scale, with a score of 0 representing absence of symptoms and a score of 3 representing a severe condition. The global clinical evaluation is made on a 6-point scale, with a score of 0 representing absence of symptom and a score of 5 representing severe akathisia.

Change from Baseline of Abnormal Involuntary Movement Scale (AIMS) ResultsAt the end of Period 3 (30 Days)

The AIMS assessment consists of 10 items describing symptoms of dyskinesia. Facial and oral movements (items 1 through 4), extremity movements (items 5 and 6), and trunk movements (item 7) are observed unobtrusively while the subject is at rest, and the investigator also makes global judgments on the subject's dyskinesias (items 8 through 10). Each item is rated on a 5-point scale, with a score of 0 representing absence of symptoms (for item 10, no awareness), and a score of 4 indicating a severe condition (for item 10, awareness, severe distress). In addition, the AIMS includes 2 yes/no questions that address the subject's dental status. The AIMS Movement Rating Score is defined as the sum of items 1 through 7 (ie, items 1 through 4, facial and oral movements; items 5 and 6, extremity movements; and item 7, trunk movements).

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Hassman Research Institute

🇺🇸

Marlton, New Jersey, United States

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