Title
Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia
A Double-Blind, Placebo-Controlled Randomized Study to Assess the Safety, Tolerability, and Pharmacokinetics of EVP-6124 in Participants With Schizophrenia on Stable Monotherapy With Selected Antipsychotics
Phase
Phase 1Lead Sponsor
FORUM Pharmaceuticals IncStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Schizophrenia Schizoaffective Disorder Central Nervous System DiseasesIntervention/Treatment
encenicline olanzapine risperidone paliperidone aripiprazole ...Study Participants
21This 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.
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.
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.
Matching placebo was administered as one capsule per day for 21 days.
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
Inclusion Criteria: Male or female aged 18 to 55 years (both inclusive). Females must be surgically sterile, post-menopausal, or using reliable contraception and have negative pregnancy tests at screening and at Day -1. A clinical diagnosis of schizophrenia or schizoaffective disorder and prescribed a stable dose of 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) for a minimum of 2 weeks before initial screening. In good general health and expected to complete the clinical trial as designed. Body Mass Index (BMI) of 18 kg/m^2 to 38 kg/m^2 (both inclusive) at screening. Adequate hearing, vision, and language skills to perform the cognitive testing and other procedures specified in the protocol. Voluntarily provided informed consent and signed an informed consent form (ICF) indicating that the purpose of the study was explained, and was willing and able to adhere to the study regimen and study procedures described in the ICF, including all confinement requirements. Negative urine drug screen at screening and inpatient observation baseline period (Day -6), except for a short-acting benzodiazepine if prescribed for insomnia. Fluent in English (speaking, writing, and reading). Exclusion Criteria: Female subject who was pregnant or breast-feeding. Any active clinically significant medical condition within 1 month (30 days) prior to screening. A history of substance (drug) dependence or substance or alcohol abuse within the 12 months before randomization as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). A score of >5 on any item on the PANSS (Positive and Negative Syndrome Scale) Positive subscale at baseline during the inpatient observation period (Day -1). Any laboratory test abnormalities at screening indicating hepatic or renal dysfunction, or any other laboratory test abnormalities deemed by the investigator to be clinically significant. Any hematologic malignancy or solid tumor diagnosed within 3 years prior to study entry with the exception of localized skin cancer or carcinoma in situ of the cervix. Known to have had or was a carrier of HBsAg, HCV antibody, or had a positive result to the HIV-1 and/or HIV-2 antibodies. Uncooperative with or could not complete the study procedures. Received an investigational drug within 30 days before screening. Donated blood within 30 days before randomization on Day 1.
| Event Type | Organ System | Event Term | Placebo | EVP-6124 (1.0 mg/Day) | EVP-6124 (0.3 mg/Day) |
|---|
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
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).
Blood samples for pharmacokinetic (PK) analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
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.
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.
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.
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.
