PET Trial to Evaluate Target Occupancy of CVL-231 at Muscarinic Receptors Type 4 in Brain Following Oral Dosing
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
15
Massachusetts General Hospital Translational and Clinical Research Centers
Boston, Massachusetts, United States
UZ Leuven
Leuven, Belgium
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
Time frame: Day 1
Treatment-emergent adverse events
Time frame: Upto 9 weeks
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
Number of subjects with clinical significant Clinical laboratory assessments
Time frame: Screening, Pre-scan, Day-1, Day 2 (T=24hour)
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
Number of subjects with clinically significant Physical and neurological examination results
Time frame: Screening, Day-1 pre-scan, Day-1, Day 2
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)
Time frame: Screening, Day-1, Day 2, Day 10
Cmax during scan for CVL-231
Max CVL-231 concentration during PET scan
Time frame: Day 1 (0.5, 1.5 and 2.0 hours)
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AUCscan duration for CVL-231
AUC for CVL-231 during PET scan
Time frame: Day 1 (0.5, 1.5 and 2.0 hours)
Cavg/Scan duration for CVL-231
Average CVL-231 concentration during scan
Time frame: Day 1 (0.5, 1.5 and 2.0 hours)
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)
Time frame: Day 1