Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia

• Sponsor: FORUM Pharmaceuticals Inc (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01556763
• Collaborator: (none)
• Enrollment: 21
• Location: 1
• Arms: 3
• Duration (Months): 4
• Patients Per Site Per Month: 5.2

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder; Central Nervous System Diseases	Drug: EVP-6124 (0.3 mg/day); Drug: EVP-6124 (1.0 mg/day); Drug: Placebo; Drug: Antipsychotic therapy	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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 Start Date: Apr 1, 2008
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Matching placebo was administered as one capsule per day for 21 days.	Drug: Placebo; Matching placebo was administered as one capsule per day for 21 days.; Drug: Antipsychotic therapy; 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.
Experimental: EVP-6124 (1.0 mg/day) EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.	Drug: EVP-6124 (1.0 mg/day); EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.; Drug: Antipsychotic therapy; 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.
Experimental: EVP-6124 (0.3 mg/day) EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.	Drug: EVP-6124 (0.3 mg/day); EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.; Drug: Antipsychotic therapy; 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.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator. [Screening (Day -5 for continuous cardiac monitoring) to Day 22]

   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).

2. EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole [Days 1 and 21]

   Blood samples for pharmacokinetic (PK) analyses were taken before dosing with EVP-6124 on Days 1 and 21.

3. EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole [Days 1 and 21]

   Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

4. EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole [Days 1 and 21]

   Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

5. EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole [Days 1 and 21]

   Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

6. EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone [Days 1 and 21]

   Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

7. EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone [Days 1 and 21]

   Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

8. EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone [Days 1 and 21]

   Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

9. EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone [Days 1 and 21]

   Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.

Secondary Outcome Measures

1. N100 Gating Ratio [Days -1 to 20]

   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.

2. P50 Amplitude Difference [Days -1 to 20]

   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.

3. MMN Summed Amplitude [Days -1 to 20]

   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.

4. P300 Peak Amplitude [Days -1 to 20]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Research Institute	Wichita	Kansas	United States	67211

Sponsors and Collaborators

• FORUM Pharmaceuticals Inc

Investigators

• Principal Investigator: Sheldon H. Preskorn, M.D., Clinical Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: FORUM Pharmaceuticals Inc
• ClinicalTrials.gov Identifier: NCT01556763
• Other Study ID Numbers: EVP-6124-005
• First Posted: Mar 16, 2012
• Last Update Posted: Jun 21, 2012
• Last Verified: May 1, 2012

• Keywords provided by FORUM Pharmaceuticals Inc: Schizophrenia; Schizoaffective; CNS
• Additional relevant MeSH terms: Nervous System Diseases; Central Nervous System Diseases; Schizophrenia; Psychotic Disorders; Antipsychotic Agents

Study Results

Participant Flow

Arm/Group Title	Placebo	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group 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.
Period Title: Overall Study
STARTED	4	9	8
COMPLETED	4	8	8
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	Placebo	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)	Total
Arm/Group 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.	Total of all reporting groups
Overall Participants	4	9	8	21
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	4 100%	9 100%	8 100%	21 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.0 (11.6)	43.1 (11.0)	51.4 (6.9)	45.7 (10.4)
Sex: Female, Male (Count of Participants)
Female	0 0%	3 33.3%	3 37.5%	6 28.6%
Male	4 100%	6 66.7%	5 62.5%	15 71.4%
Region of Enrollment (participants) [Number]
United States	4 100%	9 100%	8 100%	21 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized patients who ingested at least one dose of study drug or placebo.

Arm/Group Title	Placebo	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group 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.
Measure Participants	4	9	8
Serious Adverse Events	0 (0) 0%	0 (0) 0%	1 (0) 12.5%
Non-Serious Adverse Events	0 (0) 0%	5 (0) 55.6%	5 (0) 62.5%
No Adverse Events Reported	4 (0) 100%	4 (0) 44.4%	3 (0) 37.5%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients receiving aripiprazole.

Arm/Group Title	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group Description	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.
Measure Participants	7	3
Day 1	581.0 (149.8)	210.0 (39.3)
Day 21	2058.6 (393.2)	968.3 (90.1)

3. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients receiving aripiprazole.

Arm/Group Title	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group Description	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.
Measure Participants	7	3
Day 1	8.0	8.0
Day 21	6.0	8.0

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients receiving aripiprazole.

Arm/Group Title	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group Description	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.
Measure Participants	7	3
Day 1	10,966 (2831)	3838 (1044)
Day 21	42,042 (9623)	20,560 (2699)

5. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Patients receiving aripiprazole for whom blood samples were available for analysis.

Arm/Group Title	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group Description	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.
Measure Participants	1	1
Day 1	39.0 (NA)	43.1 (NA)
Day 21	NA (NA)	116.6 (NA)

6. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients receiving paliperidone/risperidone.

Arm/Group Title	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group Description	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.
Measure Participants	1	5
Day 1	315.0 (NA)	165.0 (40.2)
Day 21	1510.0 (NA)	545.4 (130.2)

7. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients receiving paliperidone/risperidone.

Arm/Group Title	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group Description	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.
Measure Participants	1	5
Day 1	6.0	8.0
Day 21	6.0	8.0

8. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

All patients receiving paliperidone/risperidone.

Arm/Group Title	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group Description	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.
Measure Participants	1	5
Day 1	6359 (NA)	3110 (852)
Day 21	33,042 (NA)	11,888 (3095)

9. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Patients receiving paliperidone/risperidone for whom blood samples were available for analysis.

Arm/Group Title	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group Description	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.
Measure Participants	1	2
Day 1	92.0 (NA)	45.8 (17.7)
Day 21	NA (NA)	78.1 (8.3)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Subjects providing valid and measurable N100 responses.

Arm/Group Title	Placebo	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group 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.
Measure Participants	2	5	5
Mean (Standard Error) [ratio]	1.648 (0.29)	0.801 (0.19)	0.951 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, EVP-6124 (1.0 mg/Day)
	Comments	Baseline value was the covariate and all values obtained during the treatment period were averaged together. This value was adjusted by regression against the baseline and estimation of a new value as if all subjects possessed the same baseline.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.10
	Comments
	Method	ANCOVA
	Comments

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Subjects providing valid and measurable P50 responses.

Arm/Group Title	Placebo	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group 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.
Measure Participants	2	5	5
Mean (Standard Error) [microvolts]	-0.17 (0.38)	0.67 (0.21)	-0.06 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, EVP-6124 (1.0 mg/Day)
	Comments	Baseline value was the covariate and all values obtained during the treatment period were averaged together. This value was adjusted by regression against the baseline and estimation of a new value as if all subjects possessed the same baseline.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.07
	Comments
	Method	ANCOVA
	Comments

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Subjects providing valid and measurable MMN responses.

Arm/Group Title	Placebo	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group 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.
Measure Participants	4	8	7
Mean (Standard Error) [microvolts]	0.14 (0.33)	-1.15 (0.24)	-0.61 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, EVP-6124 (1.0 mg/Day), EVP-6124 (0.3 mg/Day)
	Comments	Baseline value was the covariate and all values obtained during the treatment period were averaged together. This value was adjusted by regression against the baseline and estimation of a new value as if all subjects possessed the same baseline.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.02
	Comments
	Method	ANCOVA
	Comments

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Subjects providing valid and measurable P300 responses.

Arm/Group Title	Placebo	EVP-6124 (1.0 mg/Day)	EVP-6124 (0.3 mg/Day)
Arm/Group 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.
Measure Participants	4	8	7
Mean (Standard Error) [microvolts]	-0.3 (0.31)	1.08 (0.22)	0.78 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, EVP-6124 (1.0 mg/Day), EVP-6124 (0.3 mg/Day)
	Comments	Baseline value was the covariate and all values obtained during the treatment period were averaged together. This value was adjusted by regression against the baseline and estimation of a new value as if all subjects possessed the same baseline.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.008
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Screening to Day 22
Arm/Group Title	Placebo		EVP-6124 (1.0 mg/Day)		EVP-6124 (0.3 mg/Day)
Arm/Group 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.
All Cause Mortality
	Placebo		EVP-6124 (1.0 mg/Day)		EVP-6124 (0.3 mg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		EVP-6124 (1.0 mg/Day)		EVP-6124 (0.3 mg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/9 (0%)		1/8 (12.5%)
Psychiatric disorders
Psychiatric symptom	0/4 (0%)	0	0/9 (0%)	0	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Placebo		EVP-6124 (1.0 mg/Day)		EVP-6124 (0.3 mg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		5/9 (55.6%)		5/8 (62.5%)
Infections and infestations
Tinea cruris	0/4 (0%)	0	0/9 (0%)	0	1/8 (12.5%)	1
Investigations
Neutrophil count increased	0/4 (0%)	0	1/9 (11.1%)	1	0/8 (0%)	0
White blood cell count increased	0/4 (0%)	0	1/9 (11.1%)	1	0/8 (0%)	0
Psychiatric disorders
Psychiatric symptom	0/4 (0%)	0	0/9 (0%)	0	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Skin erosion	0/4 (0%)	0	0/9 (0%)	0	1/8 (12.5%)	1
Skin irritation	0/4 (0%)	0	5/9 (55.6%)	5	5/8 (62.5%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.