Clinical trial NCT04787302: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Schizophrenia
Keywords: Schizophrenia
PET
Healthy Volunteer
Lead sponsor: Cerevel Therapeutics, LLC
Sponsor class: INDUSTRY
First posted: 2021-03-08
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: M4 receptor occupancy in the striatum following single oral doses of CVL-231 in healthy adult subjects
timeFrame: Day 1
Secondary outcomes:
measure: Treatment-emergent adverse events
timeFrame: Upto 9 weeks
measure: Number of subjects with Clinically significant changes in Electrocardiogram
timeFrame: 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
measure: Number of subjects with clinical significant Clinical laboratory assessments
timeFrame: Screening, Pre-scan, Day-1, Day 2 (T=24hour)
measure: Number of subjects with Clinically significant changes in Vital signs
timeFrame: 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
measure: Number of subjects with clinically significant Physical and neurological examination results
timeFrame: Screening, Day-1 pre-scan, Day-1, Day 2
measure: Suicidality assessed using the Columbia-Suicide Severity Rating Scale
timeFrame: Screening, Day-1, Day 2, Day 10
measure: Cmax during scan for CVL-231
timeFrame: Day 1 (0.5, 1.5 and 2.0 hours)
measure: AUCscan duration for CVL-231
timeFrame: Day 1 (0.5, 1.5 and 2.0 hours)
measure: Cavg/Scan duration for CVL-231
timeFrame: Day 1 (0.5, 1.5 and 2.0 hours)
measure: Model estimated Emax and EC50 at M4 receptors in striatum for CVL-231
timeFrame: Day 1
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital Translational and Clinical Research Centers
state: Massachusetts
city: Leuven
country: Belgium
facility: UZ Leuven
Study officials:
affiliation: Cerevel Therapeutics, LLC
name: Matthew Leoni, MD, MBA
role: STUDY_DIRECTOR
References: