Substance Use Disorders (SUD)
Conditions
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.
Interventions
DRUGCVL-936
CVL-936
DRUGMatching Placebo
Placebo matching CVL-936
Sponsors
Cerevel Therapeutics, LLC
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
A sample size of 9 subjects per cohort has been chosen based on the need to minimize exposure of humans to CVL-936 and PF-06815106 and the requirement to provide adequate safety, tolerability, and PK information at each dose. Each cohort will be conducted as a crossover design with 3 periods and each cohort will have up to 6 subjects receiving CVL-936 and 3 subjects receiving placebo within each period, with a total of approximately 18 subjects if 2 cohorts complete or a total of approximately 27 subjects if 3 cohorts complete.
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Number of Subjects with Clinically significant changes in laboratory measures | At 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 Simpson-Angus Scale (SAS) Results | At 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. |
| Change from Baseline of Abnormal Involuntary Movement Scale (AIMS) Results | At 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). |
| Change from Baseline of Barnes Akathisia Rating Scale (BARS) Results | At 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. |
Countries
United States
Outcome results
None listed