Trial Outcomes & Findings for Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia (NCT NCT01556763)
NCT ID: NCT01556763
Last Updated: 2012-06-21
Results Overview
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).
COMPLETED
PHASE1
21 participants
Screening (Day -5 for continuous cardiac monitoring) to Day 22
2012-06-21
Participant Flow
Participant milestones
| Measure |
Placebo
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
9
|
8
|
|
Overall Study
COMPLETED
|
4
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Placebo
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
Baseline Characteristics
Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Schizophrenia
Baseline characteristics by cohort
| Measure |
EVP-6124 (1.0 mg/Day)
n=9 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
Placebo
n=4 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
n=8 Participants
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
Total
n=21 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
8 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age Continuous
|
43.1 years
STANDARD_DEVIATION 11.0 • n=7 Participants
|
40.0 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
51.4 years
STANDARD_DEVIATION 6.9 • n=5 Participants
|
45.7 years
STANDARD_DEVIATION 10.4 • n=4 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
5 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=7 Participants
|
4 participants
n=5 Participants
|
8 participants
n=5 Participants
|
21 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Screening (Day -5 for continuous cardiac monitoring) to Day 22Population: All randomized patients who ingested at least one dose of study drug or placebo.
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).
Outcome measures
| Measure |
Placebo
n=4 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=9 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
n=8 Participants
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
No Adverse Events Reported
|
4 participants
0
|
4 participants
0
|
3 participants
0
|
|
Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
Serious Adverse Events
|
0 participants
0
|
0 participants
0
|
1 participants
0
|
|
Number of Participants With Serious and Non-serious Adverse Events Spontaneously Reported by Subject and/or Observed by Investigator.
Non-Serious Adverse Events
|
0 participants
0
|
5 participants
0
|
5 participants
0
|
PRIMARY outcome
Timeframe: Days 1 and 21Population: All patients receiving aripiprazole.
Blood samples for pharmacokinetic (PK) analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Outcome measures
| Measure |
Placebo
n=7 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=3 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole
Day 1
|
581.0 pg/mL
Standard Deviation 149.8
|
210.0 pg/mL
Standard Deviation 39.3
|
—
|
|
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Aripiprazole
Day 21
|
2058.6 pg/mL
Standard Deviation 393.2
|
968.3 pg/mL
Standard Deviation 90.1
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 21Population: All patients receiving aripiprazole.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Outcome measures
| Measure |
Placebo
n=7 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=3 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole
Day 21
|
6.0 hr
Interval 2.0 to 8.0
|
8.0 hr
Interval 1.0 to 8.0
|
—
|
|
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Aripiprazole
Day 1
|
8.0 hr
Interval 2.0 to 8.0
|
8.0 hr
Interval 6.0 to 8.0
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 21Population: All patients receiving aripiprazole.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Outcome measures
| Measure |
Placebo
n=7 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=3 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole
Day 1
|
10,966 pg*hr/mL
Standard Deviation 2831
|
3838 pg*hr/mL
Standard Deviation 1044
|
—
|
|
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Aripiprazole
Day 21
|
42,042 pg*hr/mL
Standard Deviation 9623
|
20,560 pg*hr/mL
Standard Deviation 2699
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 21Population: Patients receiving aripiprazole for whom blood samples were available for analysis.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=1 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole
Day 1
|
39.0 hr
Standard Deviation NA
Data for only one patient were available.
|
43.1 hr
Standard Deviation NA
Data for only one patient were available.
|
—
|
|
EVP-6124 Half-life (T[1/2]), Patients on Aripiprazole
Day 21
|
NA hr
Standard Deviation NA
The patient withdrew consent after receiving study drug for 3 days.
|
116.6 hr
Standard Deviation NA
Data for only one patient were available.
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 21Population: All patients receiving paliperidone/risperidone.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=5 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone
Day 1
|
315.0 pg/mL
Standard Deviation NA
Data for only one patient were available.
|
165.0 pg/mL
Standard Deviation 40.2
|
—
|
|
EVP-6124 Maximum Plasma Concentration (Cmax), Patients on Paliperidone/Risperidone
Day 21
|
1510.0 pg/mL
Standard Deviation NA
Data for only one patient were available.
|
545.4 pg/mL
Standard Deviation 130.2
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 21Population: All patients receiving paliperidone/risperidone.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=5 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
Day 1
|
6.0 hr
Data for only one patient were available.
|
8.0 hr
Interval 6.0 to 8.0
|
—
|
|
EVP-6124 Time to Maximum Concentration (Tmax), Patients on Paliperidone/Risperidone
Day 21
|
6.0 hr
Data for only one patient were available.
|
8.0 hr
Interval 8.0 to 8.0
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 21Population: All patients receiving paliperidone/risperidone.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=5 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone
Day 1
|
6359 pg*hr/ml
Standard Deviation NA
Data for only one patient were available.
|
3110 pg*hr/ml
Standard Deviation 852
|
—
|
|
EVP-6124 Area Under the Curve (AUC[0-24 h]), Patients on Paliperidone/Risperidone
Day 21
|
33,042 pg*hr/ml
Standard Deviation NA
Data for only one patient were available.
|
11,888 pg*hr/ml
Standard Deviation 3095
|
—
|
PRIMARY outcome
Timeframe: Days 1 and 21Population: Patients receiving paliperidone/risperidone for whom blood samples were available for analysis.
Blood samples for PK analyses were taken before dosing with EVP-6124 on Days 1 and 21.
Outcome measures
| Measure |
Placebo
n=1 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=2 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone
Day 1
|
92.0 hr
Standard Deviation NA
Data for only one patient were available.
|
45.8 hr
Standard Deviation 17.7
|
—
|
|
EVP-6124 Half-life (T[1/2]), Patients on Paliperidone/Risperidone
Day 21
|
NA hr
Standard Deviation NA
Sample not analyzed.
|
78.1 hr
Standard Deviation 8.3
|
—
|
SECONDARY outcome
Timeframe: Days -1 to 20Population: Subjects providing valid and measurable N100 responses.
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.
Outcome measures
| Measure |
Placebo
n=2 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=5 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
n=5 Participants
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
N100 Gating Ratio
|
1.648 ratio
Standard Error 0.29
|
0.801 ratio
Standard Error 0.19
|
0.951 ratio
Standard Error 0.20
|
SECONDARY outcome
Timeframe: Days -1 to 20Population: Subjects providing valid and measurable P50 responses.
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.
Outcome measures
| Measure |
Placebo
n=2 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=5 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
n=5 Participants
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
P50 Amplitude Difference
|
-0.17 microvolts
Standard Error 0.38
|
0.67 microvolts
Standard Error 0.21
|
-0.06 microvolts
Standard Error 0.25
|
SECONDARY outcome
Timeframe: Days -1 to 20Population: Subjects providing valid and measurable MMN responses.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=8 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
n=7 Participants
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
MMN Summed Amplitude
|
0.14 microvolts
Standard Error 0.33
|
-1.15 microvolts
Standard Error 0.24
|
-0.61 microvolts
Standard Error 0.25
|
SECONDARY outcome
Timeframe: Days -1 to 20Population: Subjects providing valid and measurable P300 responses.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=8 Participants
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
n=7 Participants
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
P300 Peak Amplitude
|
-0.3 microvolts
Standard Error 0.31
|
1.08 microvolts
Standard Error 0.22
|
0.78 microvolts
Standard Error 0.24
|
Adverse Events
Placebo
EVP-6124 (1.0 mg/Day)
EVP-6124 (0.3 mg/Day)
Serious adverse events
| Measure |
Placebo
n=4 participants at risk
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=9 participants at risk
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
n=8 participants at risk
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
Psychiatric disorders
Psychiatric symptom
|
0.00%
0/4 • Screening to Day 22
|
0.00%
0/9 • Screening to Day 22
|
12.5%
1/8 • Number of events 1 • Screening to Day 22
|
Other adverse events
| Measure |
Placebo
n=4 participants at risk
Matching placebo was administered as one capsule per day for 21 days.
|
EVP-6124 (1.0 mg/Day)
n=9 participants at risk
EVP-6124 was administered as one 1.0 mg capsule per day for 21 days.
|
EVP-6124 (0.3 mg/Day)
n=8 participants at risk
EVP-6124 was administered as one 0.3 mg capsule per day for 21 days.
|
|---|---|---|---|
|
Infections and infestations
Tinea cruris
|
0.00%
0/4 • Screening to Day 22
|
0.00%
0/9 • Screening to Day 22
|
12.5%
1/8 • Number of events 1 • Screening to Day 22
|
|
Investigations
Neutrophil count increased
|
0.00%
0/4 • Screening to Day 22
|
11.1%
1/9 • Number of events 1 • Screening to Day 22
|
0.00%
0/8 • Screening to Day 22
|
|
Investigations
White blood cell count increased
|
0.00%
0/4 • Screening to Day 22
|
11.1%
1/9 • Number of events 1 • Screening to Day 22
|
0.00%
0/8 • Screening to Day 22
|
|
Psychiatric disorders
Psychiatric symptom
|
0.00%
0/4 • Screening to Day 22
|
0.00%
0/9 • Screening to Day 22
|
12.5%
1/8 • Number of events 1 • Screening to Day 22
|
|
Skin and subcutaneous tissue disorders
Skin erosion
|
0.00%
0/4 • Screening to Day 22
|
0.00%
0/9 • Screening to Day 22
|
12.5%
1/8 • Number of events 1 • Screening to Day 22
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/4 • Screening to Day 22
|
55.6%
5/9 • Number of events 5 • Screening to Day 22
|
62.5%
5/8 • Number of events 5 • Screening to Day 22
|
Additional Information
Maria Gawryl, Ph.D., Vice President, Regulatory Affairs & Drug Development
EnVivo Pharmaceuticals, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER