Back to resultsSafety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia
Primary Purpose
Schizophrenia, Schizoaffective Disorder, Central Nervous System Diseases
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
EVP-6124 (0.3 mg/day)
EVP-6124 (1.0 mg/day)
Placebo
Antipsychotic therapy
Sponsored by
About this trial
This is an interventional treatment trial for Schizophrenia focused on measuring Schizophrenia, Schizoaffective, CNS
Eligibility Criteria
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.
Sites / Locations
- Clinical Research Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Placebo Comparator
Experimental
Experimental
Arm Label
Placebo
EVP-6124 (1.0 mg/day)
EVP-6124 (0.3 mg/day)
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
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.
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.
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.
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.
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.
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
Blood samples for PK analyses were taken before dosing with EVP-6124 on 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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01556763
Brief Title
Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
August 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FORUM Pharmaceuticals Inc
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder, Central Nervous System Diseases
Keywords
Schizophrenia, Schizoaffective, CNS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo was administered as one capsule per day for 21 days.
Arm Title
EVP-6124 (1.0 mg/day)
Arm Type
Experimental
Arm Description
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
Arm Title
EVP-6124 (0.3 mg/day)
Arm Type
Experimental
Arm Description
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
Intervention Type
Drug
Intervention Name(s)
EVP-6124 (0.3 mg/day)
Intervention Description
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
Intervention Type
Drug
Intervention Name(s)
EVP-6124 (1.0 mg/day)
Intervention Description
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo was administered as one capsule per day for 21 days.
Intervention Type
Drug
Intervention Name(s)
Antipsychotic therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
Description
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
Title
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole
Description
Blood samples for pharmacokinetic (PK) analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame
Days 1 and 21
Title
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole
Description
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame
Days 1 and 21
Title
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole
Description
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame
Days 1 and 21
Title
EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole
Description
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame
Days 1 and 21
Title
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone
Description
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame
Days 1 and 21
Title
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
Description
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame
Days 1 and 21
Title
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone
Description
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame
Days 1 and 21
Title
EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone
Description
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame
Days 1 and 21
Secondary Outcome Measure Information:
Title
N100 Gating Ratio
Description
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
Title
P50 Amplitude Difference
Description
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
Title
MMN Summed Amplitude
Description
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
Title
P300 Peak Amplitude
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sheldon H. Preskorn, M.D.
Organizational Affiliation
Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Research Institute
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67211
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24419307
Citation
Preskorn SH, Gawryl M, Dgetluck N, Palfreyman M, Bauer LO, Hilt DC. Normalizing effects of EVP-6124, an alpha-7 nicotinic partial agonist, on event-related potentials and cognition: a proof of concept, randomized trial in patients with schizophrenia. J Psychiatr Pract. 2014 Jan;20(1):12-24. doi: 10.1097/01.pra.0000442935.15833.c5.
Results Reference
derived
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Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia
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