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

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

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.

Study Overview

• Status: Terminated
• Conditions: Substance Use Disorders (SUD)
• Intervention / Treatment: Drug: CVL-936; Drug: Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Marlton, New Jersey, United States, 08053
      • Hassman Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: QUADRUPLE

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active Comparator: Group 1 Period 1: 0.5mg CVL-936; Oral suspension/solution	Drug: CVL-936; CVL-936
PLACEBO_COMPARATOR: Placebo Comparator: Group 1 Period 1: 0.5mg Matching Placebo; Matching Placebo; Oral suspension/solution	Drug: Matching Placebo; Placebo matching CVL-936
ACTIVE_COMPARATOR: Active Comparator: Group 1 Period 2:TBD mg CVL-936; Oral suspension/solution	Drug: CVL-936; CVL-936
PLACEBO_COMPARATOR: Placebo Comparator: Group 1 Period 2:TBD mg Matching Placebo; Matching Placebo; Oral suspension/solution	Drug: Matching Placebo; Placebo matching CVL-936
ACTIVE_COMPARATOR: Active Comparator: Group 1 Period 3:TBD mg CVL-936; Oral suspension/solution	Drug: CVL-936; CVL-936
PLACEBO_COMPARATOR: Placebo Comparator: Group 1 Period 3:TBD mg Matching Placebo; Matching Placebo; Oral suspension/solution	Drug: Matching Placebo; Placebo matching CVL-936
ACTIVE_COMPARATOR: Active Comparator: Group 2 Period 1:TBD mg CVL-936; Oral suspension/solution	Drug: CVL-936; CVL-936
PLACEBO_COMPARATOR: Placebo Comparator: Group 2 Period 1:TBD mg Matching Placebo; Matching Placebo; Oral suspension/solution	Drug: Matching Placebo; Placebo matching CVL-936
ACTIVE_COMPARATOR: Active Comparator: Group 2 Period 2:TBD mg CVL-936; Oral suspension/solution	Drug: CVL-936; CVL-936
PLACEBO_COMPARATOR: Placebo Comparator: Group 2 Period 2:TBD mg Matching Placebo; Matching Placebo; Oral suspension/solution	Drug: Matching Placebo; Placebo matching CVL-936
ACTIVE_COMPARATOR: Active Comparator: Group 2 Period 3:TBD mg CVL-936; Oral suspension/solution	Drug: CVL-936; CVL-936
PLACEBO_COMPARATOR: Placebo Comparator: Group 2 Period 3:TBD mg Matching Placebo; Matching Placebo; Oral suspension/solution	Drug: Matching Placebo; Placebo matching CVL-936
ACTIVE_COMPARATOR: Active Comparator: Group 3: TBD mg CVL-936; Oral suspension/solution	Drug: CVL-936; CVL-936
PLACEBO_COMPARATOR: Placebo Comparator: Group 3: TBD mg Matching Placebo; Matching Placebo; Oral suspension/solution	Drug: Matching Placebo; Placebo matching CVL-936

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Cerevel Therapeutics, LLC
• Investigators: Study Director: Matt Leoni, MD, Cerevel Therapeutics, LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 16, 2019
• Primary Completion (ACTUAL): March 6, 2020
• Study Completion (ACTUAL): May 21, 2020

Study Registration Dates

• First Submitted: January 10, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (ACTUAL): January 18, 2020

Study Record Updates

• Last Update Posted (ACTUAL): June 22, 2020
• Last Update Submitted That Met QC Criteria: June 18, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: CVL-936-HV-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No