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PET Trial to Evaluate Target Occupancy of CVL-231 on Brain Receptors Following Oral Dosing

Primary Purpose

Schizophrenia

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

CVL-231

About this trial

This is an interventional basic science trial for Schizophrenia focused on measuring Schizophrenia, PET, Healthy Volunteer

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Healthy male subjects and female subjects of nonchildbearing potential, ages 18 to 55 years, inclusive, at the time of signing the ICF
Sexually active men with a pregnant or a nonpregnant partner of childbearing potential must agree to use a double-barrier method of birth control, including a condom, and practice contraception during treatment and through 7 days post dose
Capable of providing informed consent and following study requirements

Exclusion Criteria:

Subjects who answer yes on the C-SSRS or, in the opinion of the investigator, present a serious risk of suicide
Subjects with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological disease
Subjects with a 12-lead ECG demonstrating either of the following (average of 3 ECGs obtained at the Screening Visit):
- QT interval corrected for heart rate using Fridericia's formula >450 msec
- Left ventricular hypertrophy
Orthostatic hypotension, which is defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the immediately previous supine/semi-recumbent blood pressure at Screening or at the prescan time point prior to baseline PET scan.
Subjects with a current or past personal history of any psychiatric disorder as classified by DSM-5 criteria or immediate family members with any psychiatric disorder as classified by DSM-5 criteria that require treatment
Subjects with a history of substance or alcohol-use disorder (DSM-5 criteria) within 2 years prior to signing the ICF
Subjects with other abnormal laboratory test results, vital sign results, or ECG findings
Subjects who currently use or have used tobacco or nicotine-containing products within 30 days prior to signing the ICF
Subjects with history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure (5 rem per year)
Subjects with any anatomical abnormality in the head that would either preclude or tend to confound the analysis of study data, including any clinically significant abnormal findings from MRI of the head
Current, past or anticipated exposure to radiation in the workplace
Any subject with a significant acute illness within 7 days prior to administration of study drug or have had a major illness or hospitalization within 1 month prior to administration of study drug
Any subject who, in the opinion of the sponsor, investigator, or medical monitor, should not participate in the trial

Sites / Locations

Massachusetts General Hospital Translational and Clinical Research Centers
UZ Leuven

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CVL-231

Arm Description

Outcomes

Primary Outcome Measures

M4 receptor occupancy in the striatum following single oral doses of CVL-231 in healthy adult subjects

Fraction of M4 receptors occupied by CVL-231 doses

Secondary Outcome Measures

Treatment-emergent adverse events

Number of subjects with Clinically significant changes in Electrocardiogram

Number of subjects with clinical significant Clinical laboratory assessments

Number of subjects with Clinically significant changes in Vital signs

Number of subjects with clinically significant Physical and neurological examination results

Suicidality assessed using the Columbia-Suicide Severity Rating Scale

Suicidality will be monitored during the trial using the Columbia - Suicide Severity Rating Scale (C-SSRS)

Cmax during scan for CVL-231

Max CVL-231 concentration during PET scan

AUCscan duration for CVL-231

AUC for CVL-231 during PET scan

Cavg/Scan duration for CVL-231

Average CVL-231 concentration during scan

Model estimated Emax and EC50 at M4 receptors in striatum for CVL-231

Model estimated values for Maximum possible binding (Emax) and CVL-231 concentrations required from hal-maximal binding (EC50)

Full Information

NCT ID

NCT04787302

First Posted

February 1, 2021

Last Updated

July 25, 2023

Sponsor

Cerevel Therapeutics, LLC

1. Study Identification

Unique Protocol Identification Number

NCT04787302

Brief Title

PET Trial to Evaluate Target Occupancy of CVL-231 on Brain Receptors Following Oral Dosing

Official Title

A Phase 1, Open-label Trial to Evaluate Target Occupancy of CVL-231 at Muscarinic Receptors Type 4 in Brain Following Single Oral Doses Using Positron Emission Tomography in Healthy Adult Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Completed

Study Start Date

June 1, 2021 (Actual)

Primary Completion Date

July 14, 2023 (Actual)

Study Completion Date

July 14, 2023 (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

5. Study Description

Brief Summary

PET Trial to Evaluate Target Occupancy of CVL-231 at Muscarinic Receptors Type 4 in Brain Following Oral Dosing

Detailed Description

CVL-231 is a muscarinic acetylcholine receptor (mAChR) activator that selectively binds to the M4 muscarinic receptor subtype (M4 mAChR). CVL-231 is being developed for treatment of psychosis in schizophrenia. The aim of this trial is to characterize the relationship between the M4 receptor occupancy in different regions of the brain following a single oral doses of CVL-231 in healthy adult subjects by positron emission tomography (PET) using the radioligand [11C]MK-6884.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

Keywords

Schizophrenia, PET, Healthy Volunteer

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CVL-231

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

CVL-231

Other Intervention Name(s)

PF-06852231

Intervention Description

Cohort 1: 30mg dose of CVL-231

Intervention Type

Drug

Intervention Name(s)

CVL-231

Other Intervention Name(s)

PF-06852231

Intervention Description

Cohort 2: CVL-231 dose to be decided based on results of Cohort 1 or trial may be concluded

Intervention Type

Drug

Intervention Name(s)

CVL-231

Other Intervention Name(s)

PF-06852231

Intervention Description

Cohort 3: CVL-231 dose to be decided based on results of Cohorts 1 and/or 2

Primary Outcome Measure Information:

Title

M4 receptor occupancy in the striatum following single oral doses of CVL-231 in healthy adult subjects

Description

Fraction of M4 receptors occupied by CVL-231 doses

Time Frame

Day 1

Secondary Outcome Measure Information:

Title

Treatment-emergent adverse events

Time Frame

Upto 9 weeks

Title

Number of subjects with Clinically significant changes in Electrocardiogram

Time Frame

Screening, Pre-scan, Day-1, Day 1 (T=0hour), Day 1 (T=0.5hour), Day 1 (T=3.0hour), Day 2 (T=24hour), Day 10

Title

Number of subjects with clinical significant Clinical laboratory assessments

Time Frame

Screening, Pre-scan, Day-1, Day 2 (T=24hour)

Title

Number of subjects with Clinically significant changes in Vital signs

Time Frame

Screening, Day-1 (T=1hour), Day-1 (T=1.5hour), Day-1, Day 1 (T=0hour), Day 1(T=1.5hour), Day 1 (T=3hour), Day 1 (T=6hr), Day 1 (T=8.0), Day 2 (T-=24hr), Day 10

Title

Number of subjects with clinically significant Physical and neurological examination results

Time Frame

Screening, Day-1 pre-scan, Day-1, Day 2

Title

Suicidality assessed using the Columbia-Suicide Severity Rating Scale

Description

Suicidality will be monitored during the trial using the Columbia - Suicide Severity Rating Scale (C-SSRS)

Time Frame

Screening, Day-1, Day 2, Day 10

Title

Cmax during scan for CVL-231

Description

Max CVL-231 concentration during PET scan

Time Frame

Day 1 (0.5, 1.5 and 2.0 hours)

Title

AUCscan duration for CVL-231

Description

AUC for CVL-231 during PET scan

Time Frame

Day 1 (0.5, 1.5 and 2.0 hours)

Title

Cavg/Scan duration for CVL-231

Description

Average CVL-231 concentration during scan

Time Frame

Day 1 (0.5, 1.5 and 2.0 hours)

Title

Model estimated Emax and EC50 at M4 receptors in striatum for CVL-231

Description

Model estimated values for Maximum possible binding (Emax) and CVL-231 concentrations required from hal-maximal binding (EC50)

Time Frame

Day 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Healthy male subjects and female subjects of nonchildbearing potential, ages 18 to 55 years, inclusive, at the time of signing the ICF Sexually active men with a pregnant or a nonpregnant partner of childbearing potential must agree to use a double-barrier method of birth control, including a condom, and practice contraception during treatment and through 7 days post dose Capable of providing informed consent and following study requirements Exclusion Criteria: Subjects who answer yes on the C-SSRS or, in the opinion of the investigator, present a serious risk of suicide Subjects with a current history of significant cardiovascular, pulmonary, gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or neurological disease Subjects with a 12-lead ECG demonstrating either of the following (average of 3 ECGs obtained at the Screening Visit): QT interval corrected for heart rate using Fridericia's formula >450 msec Left ventricular hypertrophy Orthostatic hypotension, which is defined as a decrease of ≥20 mmHg in systolic blood pressure and/or a decrease of ≥10 mmHg in diastolic blood pressure after at least 3 minutes of standing compared with the immediately previous supine/semi-recumbent blood pressure at Screening or at the prescan time point prior to baseline PET scan. Subjects with a current or past personal history of any psychiatric disorder as classified by DSM-5 criteria or immediate family members with any psychiatric disorder as classified by DSM-5 criteria that require treatment Subjects with a history of substance or alcohol-use disorder (DSM-5 criteria) within 2 years prior to signing the ICF Subjects with other abnormal laboratory test results, vital sign results, or ECG findings Subjects who currently use or have used tobacco or nicotine-containing products within 30 days prior to signing the ICF Subjects with history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure (5 rem per year) Subjects with any anatomical abnormality in the head that would either preclude or tend to confound the analysis of study data, including any clinically significant abnormal findings from MRI of the head Current, past or anticipated exposure to radiation in the workplace Any subject with a significant acute illness within 7 days prior to administration of study drug or have had a major illness or hospitalization within 1 month prior to administration of study drug Any subject who, in the opinion of the sponsor, investigator, or medical monitor, should not participate in the trial

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Matthew Leoni, MD, MBA

Organizational Affiliation

Cerevel Therapeutics, LLC

Official's Role

Study Director

Facility Information:

Facility Name

Massachusetts General Hospital Translational and Clinical Research Centers

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

UZ Leuven

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

12. IPD Sharing Statement

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PET Trial to Evaluate Target Occupancy of CVL-231 on Brain Receptors Following Oral Dosing

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