search
Back to results

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

Primary Purpose

Substance Use Disorders (SUD)

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CVL-936
Matching Placebo
Sponsored by
Cerevel Therapeutics, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Substance Use Disorders (SUD)

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Hassman Research Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm Type

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Active Comparator

Placebo Comparator

Arm Label

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

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

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

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

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

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

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

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

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

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

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

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

Active Comparator: Group 3: TBD mg CVL-936

Placebo Comparator: Group 3: TBD mg Matching Placebo

Arm Description

Oral suspension/solution

Matching Placebo; Oral suspension/solution

Oral suspension/solution

Matching Placebo; Oral suspension/solution

Oral suspension/solution

Matching Placebo; Oral suspension/solution

Oral suspension/solution

Matching Placebo; Oral suspension/solution

Oral suspension/solution

Matching Placebo; Oral suspension/solution

Oral suspension/solution

Matching Placebo; Oral suspension/solution

Oral suspension/solution

Matching Placebo; Oral suspension/solution

Outcomes

Primary Outcome Measures

Number of Subjects with reported Treatment Emergent Adverse Events (TEAEs)
Number of Subjects with Clinically significant changes in Electrocardiogram measures (PR, RR, QT and QTcF)
Number of Subjects with Clinically meaningful changes in Vital signs (Systolic and Diastolic blood pressures, heart rate, respiratory rate and body temperature)
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
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).
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.
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).
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.

Secondary Outcome Measures

Full Information

First Posted
January 10, 2020
Last Updated
June 18, 2020
Sponsor
Cerevel Therapeutics, LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT04232878
Brief Title
A Single Ascending Dose Trial of CVL-936 in Healthy Subjects
Official Title
A Phase 1, Double-Blind, Sponsor-Open, Placebo-Controlled, First-In-Human Trial To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Single Ascending Doses of CVL-936 In Healthy Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
June 2020
Overall Recruitment Status
Terminated
Why Stopped
Sufficient data has been obtained to meet current objectives
Study Start Date
December 16, 2019 (Actual)
Primary Completion Date
March 6, 2020 (Actual)
Study Completion Date
May 21, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cerevel Therapeutics, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Substance Use Disorders (SUD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active Comparator: Group 1 Period 1: 0.5mg CVL-936
Arm Type
Active Comparator
Arm Description
Oral suspension/solution
Arm Title
Placebo Comparator: Group 1 Period 1: 0.5mg Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo; Oral suspension/solution
Arm Title
Active Comparator: Group 1 Period 2:TBD mg CVL-936
Arm Type
Active Comparator
Arm Description
Oral suspension/solution
Arm Title
Placebo Comparator: Group 1 Period 2:TBD mg Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo; Oral suspension/solution
Arm Title
Active Comparator: Group 1 Period 3:TBD mg CVL-936
Arm Type
Active Comparator
Arm Description
Oral suspension/solution
Arm Title
Placebo Comparator: Group 1 Period 3:TBD mg Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo; Oral suspension/solution
Arm Title
Active Comparator: Group 2 Period 1:TBD mg CVL-936
Arm Type
Active Comparator
Arm Description
Oral suspension/solution
Arm Title
Placebo Comparator: Group 2 Period 1:TBD mg Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo; Oral suspension/solution
Arm Title
Active Comparator: Group 2 Period 2:TBD mg CVL-936
Arm Type
Active Comparator
Arm Description
Oral suspension/solution
Arm Title
Placebo Comparator: Group 2 Period 2:TBD mg Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo; Oral suspension/solution
Arm Title
Active Comparator: Group 2 Period 3:TBD mg CVL-936
Arm Type
Active Comparator
Arm Description
Oral suspension/solution
Arm Title
Placebo Comparator: Group 2 Period 3:TBD mg Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo; Oral suspension/solution
Arm Title
Active Comparator: Group 3: TBD mg CVL-936
Arm Type
Active Comparator
Arm Description
Oral suspension/solution
Arm Title
Placebo Comparator: Group 3: TBD mg Matching Placebo
Arm Type
Placebo Comparator
Arm Description
Matching Placebo; Oral suspension/solution
Intervention Type
Drug
Intervention Name(s)
CVL-936
Intervention Description
CVL-936
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Placebo matching CVL-936
Primary Outcome Measure Information:
Title
Number of Subjects with reported Treatment Emergent Adverse Events (TEAEs)
Time Frame
At the end of Period 3 (30 Days)
Title
Number of Subjects with Clinically significant changes in Electrocardiogram measures (PR, RR, QT and QTcF)
Time Frame
At the end of Period 3 (30 Days)
Title
Number of Subjects with Clinically meaningful changes in Vital signs (Systolic and Diastolic blood pressures, heart rate, respiratory rate and body temperature)
Time Frame
At the end of Period 3 (30 Days)
Title
Number of Subjects with Clinically significant changes in laboratory measures
Description
Number of subjects with clinically significant changes in hematology, serum chemistry and urinalysis will be reported
Time Frame
At the end of Period 3 (30 Days)
Title
Change from baseline of the Columbia-Suicide Severity Rating Scale (C-SSRS)
Description
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).
Time Frame
At the end of Period 3 (30 Days)
Title
Change from Baseline of Simpson-Angus Scale (SAS) Results
Description
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.
Time Frame
At the end of Period 3 (30 Days)
Title
Change from Baseline of Abnormal Involuntary Movement Scale (AIMS) Results
Description
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).
Time Frame
At the end of Period 3 (30 Days)
Title
Change from Baseline of Barnes Akathisia Rating Scale (BARS) Results
Description
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.
Time Frame
At the end of Period 3 (30 Days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 1. Healthy male subjects and female subjects of nonchildbearing potential, ages 18 to 50 years Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matt Leoni, MD
Organizational Affiliation
Cerevel Therapeutics, LLC
Official's Role
Study Director
Facility Information:
Facility Name
Hassman Research Institute
City
Marlton
State/Province
New Jersey
ZIP/Postal Code
08053
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs