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Trial record 5 of 5 for:    evp-6124, schizophrenia

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

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ClinicalTrials.gov Identifier: NCT01556763
Recruitment Status : Completed
First Posted : March 16, 2012
Results First Posted : June 21, 2012
Last Update Posted : June 21, 2012
Sponsor:
Information provided by (Responsible Party):
FORUM Pharmaceuticals Inc

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Schizophrenia
Schizoaffective Disorder
Central Nervous System Diseases
Interventions Drug: EVP-6124 (0.3 mg/day)
Drug: EVP-6124 (1.0 mg/day)
Drug: Placebo
Drug: Antipsychotic therapy
Enrollment 21
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day)
Hide 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
Reason Not Completed
Withdrawal by Subject             0             1             0
Arm/Group Title Placebo EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day) Total
Hide 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 Number of Baseline Participants 4 9 8 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 9 participants 8 participants 21 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
4
 100.0%
9
 100.0%
8
 100.0%
21
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 4 participants 9 participants 8 participants 21 participants
40.0  (11.6) 43.1  (11.0) 51.4  (6.9) 45.7  (10.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 4 participants 9 participants 8 participants 21 participants
Female
0
   0.0%
3
  33.3%
3
  37.5%
6
  28.6%
Male
4
 100.0%
6
  66.7%
5
  62.5%
15
  71.4%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 4 participants 9 participants 8 participants 21 participants
4 9 8 21
1.Primary Outcome
Title Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 4 9 8
Measure Type: Number
Unit of Measure: participants
Serious Adverse Events 0 0 1
Non-Serious Adverse Events 0 5 5
No Adverse Events Reported 4 4 3
2.Primary Outcome
Title EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving aripiprazole.
Arm/Group Title EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day)
Hide 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.
Overall Number of Participants Analyzed 7 3
Mean (Standard Deviation)
Unit of Measure: pg/mL
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
Hide Description Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame Days 1 and 21
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving aripiprazole.
Arm/Group Title EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day)
Hide 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.
Overall Number of Participants Analyzed 7 3
Median (Full Range)
Unit of Measure: hr
Day 1
8.0
(2 to 8)
8.0
(6 to 8)
Day 21
6.0
(2 to 8)
8.0
(1 to 8)
4.Primary Outcome
Title EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole
Hide Description Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame Days 1 and 21
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving aripiprazole.
Arm/Group Title EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day)
Hide 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.
Overall Number of Participants Analyzed 7 3
Mean (Standard Deviation)
Unit of Measure: pg*hr/mL
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
Hide Description Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame Days 1 and 21
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 1 1
Mean (Standard Deviation)
Unit of Measure: hr
Day 1 39.0 [1]   (NA) 43.1 [1]   (NA)
Day 21 NA [2]   (NA) 116.6 [1]   (NA)
[1]
Data for only one patient were available.
[2]
The patient withdrew consent after receiving study drug for 3 days.
6.Primary Outcome
Title EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone
Hide Description Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame Days 1 and 21
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving paliperidone/risperidone.
Arm/Group Title EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day)
Hide 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.
Overall Number of Participants Analyzed 1 5
Mean (Standard Deviation)
Unit of Measure: pg/mL
Day 1 315.0 [1]   (NA) 165.0  (40.2)
Day 21 1510.0 [1]   (NA) 545.4  (130.2)
[1]
Data for only one patient were available.
7.Primary Outcome
Title EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
Hide Description Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame Days 1 and 21
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving paliperidone/risperidone.
Arm/Group Title EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day)
Hide 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.
Overall Number of Participants Analyzed 1 5
Median (Full Range)
Unit of Measure: hr
Day 1
6.0 [1] 
(NA to NA)
8.0
(6 to 8)
Day 21
6.0 [1] 
(NA to NA)
8.0
(8 to 8)
[1]
Data for only one patient were available.
8.Primary Outcome
Title EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone
Hide Description Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame Days 1 and 21
Hide Outcome Measure Data
Hide Analysis Population Description
All patients receiving paliperidone/risperidone.
Arm/Group Title EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day)
Hide 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.
Overall Number of Participants Analyzed 1 5
Mean (Standard Deviation)
Unit of Measure: pg*hr/ml
Day 1 6359 [1]   (NA) 3110  (852)
Day 21 33,042 [1]   (NA) 11,888  (3095)
[1]
Data for only one patient were available.
9.Primary Outcome
Title EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone
Hide Description Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Time Frame Days 1 and 21
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 1 2
Mean (Standard Deviation)
Unit of Measure: hr
Day 1 92.0 [1]   (NA) 45.8  (17.7)
Day 21 NA [2]   (NA) 78.1  (8.3)
[1]
Data for only one patient were available.
[2]
Sample not analyzed.
10.Secondary Outcome
Title N100 Gating Ratio
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 2 5 5
Mean (Standard Error)
Unit of Measure: ratio
1.648  (0.29) 0.801  (0.19) 0.951  (0.20)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value =0.10
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
11.Secondary Outcome
Title P50 Amplitude Difference
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 2 5 5
Mean (Standard Error)
Unit of Measure: microvolts
-0.17  (0.38) 0.67  (0.21) -0.06  (0.25)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value =0.07
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
12.Secondary Outcome
Title MMN Summed Amplitude
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 4 8 7
Mean (Standard Error)
Unit of Measure: microvolts
0.14  (0.33) -1.15  (0.24) -0.61  (0.25)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value =0.02
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
13.Secondary Outcome
Title P300 Peak Amplitude
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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.
Overall Number of Participants Analyzed 4 8 7
Mean (Standard Error)
Unit of Measure: microvolts
-0.3  (0.31) 1.08  (0.22) 0.78  (0.24)
Show Statistical Analysis 1 Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value =0.008
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Time Frame Screening to Day 22
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo EVP-6124 (1.0 mg/Day) EVP-6124 (0.3 mg/Day)
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide 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 (0.00%)      0/9 (0.00%)      1/8 (12.50%)    
Psychiatric disorders       
Psychiatric symptom  0/4 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (0.00%)      5/9 (55.56%)      5/8 (62.50%)    
Infections and infestations       
Tinea cruris  0/4 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1
Investigations       
Neutrophil count increased  0/4 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
White blood cell count increased  0/4 (0.00%)  0 1/9 (11.11%)  1 0/8 (0.00%)  0
Psychiatric disorders       
Psychiatric symptom  0/4 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1
Skin and subcutaneous tissue disorders       
Skin erosion  0/4 (0.00%)  0 0/9 (0.00%)  0 1/8 (12.50%)  1
Skin irritation  0/4 (0.00%)  0 5/9 (55.56%)  5 5/8 (62.50%)  5
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Maria Gawryl, Ph.D., Vice President, Regulatory Affairs & Drug Development
Organization: EnVivo Pharmaceuticals, Inc.
Phone: 617-225-4264
EMail: mgawryl@envivopharma.com
Layout table for additonal information
Responsible Party: FORUM Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT01556763     History of Changes
Other Study ID Numbers: EVP-6124-005
First Submitted: March 14, 2012
First Posted: March 16, 2012
Results First Submitted: April 18, 2012
Results First Posted: June 21, 2012
Last Update Posted: June 21, 2012