This study in patients with schizophrenia is designed to provide preliminary evidence of the safety, tolerability, and pharmacokinetics as well as the effects on cognitive function of 2 doses of EVP-6124 compared with placebo when given with the patient's usual antipsychotic medication.
Study drug will be supplied as capsules and will be orally administered once daily for a total of 21 days. Eligible subjects will be admitted to an inpatient study unit on Day -6 (six days before the first dose of study drug is administered) and will remain confined to the inpatient study unit throughout the dosing phase. Safety assessments, PK sampling, and cognitive testing will be performed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
21
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
Matching placebo was administered as one capsule per day for 21 days.
Clinical Research Institute
Wichita, Kansas, United States
Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
Safety and tolerability was measured by number of reported adverse events (serious and non-serious) and repeated clinical evaluation of physical examinations, vital signs, 12-lead electrocardiogram (ECG), 24-hour continuous cardiac monitoring, and laboratory tests (hematology/blood chemistry/urinalysis).
Time frame: Screening (Day -5 for continuous cardiac monitoring) to Day 22
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole
Blood samples for pharmacokinetic (PK) analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time frame: Days 1 and 21
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time frame: Days 1 and 21
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time frame: Days 1 and 21
EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time frame: Days 1 and 21
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time frame: Days 1 and 21
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
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Concomitant therapy with antipsychotic medication (aripiprazole \[10 to 30 mg/day\], olanzapine \[10 to 20 mg/day\], paliperidone \[3 to 12 mg/day\], or risperidone \[2 to 16 mg/day\]), taken at the same time each day as the EVP-6124 dose. Patients must have been taking concomitant therapy for at least 2 weeks at a stable dose to be eligible for the study.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time frame: Days 1 and 21
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time frame: Days 1 and 21
EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time frame: Days 1 and 21
N100 Gating Ratio
N100 auditory evoked potential response (amplitude measured in microvolts) using the sensory gating paradigm. Measured by electroencephalography (EEG) as the amplitude ratio of test stimulus to conditioning stimulus. Plotted on a unitless scale of 0 to 2. Normalization is suggested by a lower value.
Time frame: Days -1 to 20
P50 Amplitude Difference
P50 auditory evoked potential response (amplitude measured in microvolts) using sensory gating paradigm. Measured by EEG as amplitude difference (conditioning stimulus minus test stimulus). Plotted on a scale of -0.2 to 0.8 microvolts. Normalization is suggested by a higher value.
Time frame: Days -1 to 20
MMN Summed Amplitude
Mismatch negativity (MMN) auditory evoked potential response (amplitude in microvolts) using orienting paradigm. Measured by EEG and calculated as the voltage difference over 100-200 msec following stimulus onset (rare stimulus minus frequent stimulus). Plotted on a scale of -1.2 to 0.2 microvolts. Normalization is suggested by a more negative value.
Time frame: Days -1 to 20
P300 Peak Amplitude
P300 auditory evoked potential response (amplitude in microvolts) using orienting paradigm. Measured by EEG and calculated as the peak amplitude over 250-500 msec following stimulus onset (rare stimulus minus frequent stimulus). Plotted on a scale of -0.4 to 1.2 microvolts. Normalization is suggested by a more positive value.
Time frame: Days -1 to 20