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

NCT04232878 | Terminated Phase 1 FDA Drug

• 1 other identifier: CVL-936-HV-001
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Substance Use Disorders (SUD)

Outcome Measures

Primary Outcomes (8)

• 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

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

  At the end of Period 3 (30 Days)

• Change from baseline of the Columbia-Suicide Severity Rating Scale (C-SSRS)

  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).

  At the end of Period 3 (30 Days)

• Change from Baseline of Simpson-Angus Scale (SAS) Results

  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.

  At the end of Period 3 (30 Days)

• Change from Baseline of Abnormal Involuntary Movement Scale (AIMS) Results

  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).

  At the end of Period 3 (30 Days)

• Change from Baseline of Barnes Akathisia Rating Scale (BARS) Results

  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.

  At the end of Period 3 (30 Days)

Study Arms (14)

Active Comparator: Group 1 Period 1: 0.5mg CVL-936

ACTIVE COMPARATOR

Oral suspension/solution

Drug: CVL-936

Placebo Comparator: Group 1 Period 1: 0.5mg Matching Placebo

PLACEBO COMPARATOR

Matching Placebo; Oral suspension/solution

Drug: Matching Placebo

Active Comparator: Group 1 Period 2:TBD mg CVL-936

ACTIVE COMPARATOR

Oral suspension/solution

Drug: CVL-936

Placebo Comparator: Group 1 Period 2:TBD mg Matching Placebo

PLACEBO COMPARATOR

Matching Placebo; Oral suspension/solution

Drug: Matching Placebo

Active Comparator: Group 1 Period 3:TBD mg CVL-936

ACTIVE COMPARATOR

Oral suspension/solution

Drug: CVL-936

Placebo Comparator: Group 1 Period 3:TBD mg Matching Placebo

PLACEBO COMPARATOR

Matching Placebo; Oral suspension/solution

Drug: Matching Placebo

Active Comparator: Group 2 Period 1:TBD mg CVL-936

ACTIVE COMPARATOR

Oral suspension/solution

Drug: CVL-936

Placebo Comparator: Group 2 Period 1:TBD mg Matching Placebo

PLACEBO COMPARATOR

Matching Placebo; Oral suspension/solution

Drug: Matching Placebo

Active Comparator: Group 2 Period 2:TBD mg CVL-936

ACTIVE COMPARATOR

Oral suspension/solution

Drug: CVL-936

Placebo Comparator: Group 2 Period 2:TBD mg Matching Placebo

PLACEBO COMPARATOR

Matching Placebo; Oral suspension/solution

Drug: Matching Placebo

Active Comparator: Group 2 Period 3:TBD mg CVL-936

ACTIVE COMPARATOR

Oral suspension/solution

Drug: CVL-936

Placebo Comparator: Group 2 Period 3:TBD mg Matching Placebo

PLACEBO COMPARATOR

Matching Placebo; Oral suspension/solution

Drug: Matching Placebo

Active Comparator: Group 3: TBD mg CVL-936

ACTIVE COMPARATOR

Oral suspension/solution

Drug: CVL-936

Placebo Comparator: Group 3: TBD mg Matching Placebo

PLACEBO COMPARATOR

Matching Placebo; Oral suspension/solution

Drug: Matching Placebo

Interventions

CVL-936 DRUG

CVL-936

Active Comparator: Group 1 Period 1: 0.5mg CVL-936; Active Comparator: Group 1 Period 2:TBD mg CVL-936; Active Comparator: Group 1 Period 3:TBD mg CVL-936; Active Comparator: Group 2 Period 1:TBD mg CVL-936; Active Comparator: Group 2 Period 2:TBD mg CVL-936; Active Comparator: Group 2 Period 3:TBD mg CVL-936; Active Comparator: Group 3: TBD mg CVL-936

Matching Placebo DRUG

Placebo matching CVL-936

Placebo Comparator: Group 1 Period 1: 0.5mg Matching Placebo; Placebo Comparator: Group 1 Period 2:TBD mg Matching Placebo; Placebo Comparator: Group 1 Period 3:TBD mg Matching Placebo; Placebo Comparator: Group 2 Period 1:TBD mg Matching Placebo; Placebo Comparator: Group 2 Period 2:TBD mg Matching Placebo; Placebo Comparator: Group 2 Period 3:TBD mg Matching Placebo; Placebo Comparator: Group 3: TBD mg Matching Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. Healthy male subjects and female subjects of nonchildbearing potential, ages 18 to 50 years

You may not qualify if:

• 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.
• Subjects with epilepsy or a history of seizures
• 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.
• Subjects with a history of hypersensitivity to any dopamine-blocker medication.

Sponsors & Collaborators

• Cerevel Therapeutics, LLC: lead

Study Sites (1)

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

MeSH Terms

Conditions

Substance-Related Disorders

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders

Study Officials

• Matt Leoni, MD

  Cerevel Therapeutics, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 18, 2020
• Study Start: December 16, 2019
• Primary Completion: March 6, 2020
• Study Completion: May 21, 2020
• Last Updated: June 22, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)