Trial Outcomes & Findings for Evaluating the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures (NCT NCT00327717)

NCT ID: NCT00327717

Last Updated: 2014-08-15

Results Overview

The median percent change in seizure frequency of all partial seizures (CP+SP+SGS) from baseline during the fixed-dose phase.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 240 participants
• Primary outcome timeframe: Baseline and 16 weeks
• Results posted on: 2014-08-15

Participant Flow

Participant milestones

Measure	Zonisamide 100 mg Tablet Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Overall Study STARTED	120	120
Overall Study COMPLETED	111	106
Overall Study NOT COMPLETED	9	14

Reasons for withdrawal

Measure	Zonisamide 100 mg Tablet Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Overall Study Adverse Event	6	6
Overall Study Lack of Efficacy	0	1
Overall Study Withdrawal by Subject	3	7

Baseline Characteristics

Evaluating the Efficacy and Safety of Zonisamide in the Treatment of Partial Seizures

Baseline characteristics by cohort

Measure	Zonisamide 100 mg Tablet n=111 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=106 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.	Total n=217 Participants Total of all reporting groups
Age, Continuous	32.72 years STANDARD_DEVIATION 12.18 • n=5 Participants	30.69 years STANDARD_DEVIATION 11.59 • n=7 Participants	31.73 years STANDARD_DEVIATION 11.89 • n=5 Participants
Sex: Female, Male Female	54 Participants n=5 Participants	43 Participants n=7 Participants	97 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	63 Participants n=7 Participants	120 Participants n=5 Participants
Race/Ethnicity, Customized Asian	120 participants n=5 Participants	97 participants n=7 Participants	217 participants n=5 Participants
Region of Enrollment China	111 participants n=5 Participants	106 participants n=7 Participants	217 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 16 weeks

Population: Full analysis set (FAS)

The median percent change in seizure frequency of all partial seizures (CP+SP+SGS) from baseline during the fixed-dose phase.

Outcome measures

Measure	Zonisamide 100 mg Tablet n=111 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=106 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Median Percent Change From Baseline in All Partial Seizure Frequency (Complex Partial Seizures (CP)+ Simple Partial Seizures (SP) + Secondary Generalization Seizures (SGS)) During the Fixed-dose Phase	-48.42 Percent Change Full Range 73.83 • Interval -100.0 to 475.0	-26.58 Percent Change Full Range 157.22 • Interval -100.0 to 1360.74

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: FAS population. Complex partial seizure patients

The Mean Percent Change in seizure frequency of CP from baseline during the fixed-dose phase.

Outcome measures

Measure	Zonisamide 100 mg Tablet n=69 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=69 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
The Mean Percent Change From Baseline in Complex Partial (CP) Seizure Frequency	-31.65 Percent Change Standard Deviation 87.28	-25.21 Percent Change Standard Deviation 68.23

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: FAS Population. Simple partial seizure patients

The Mean percent change in seizure frequency of SP from baseline during the fixed-dose phase.

Outcome measures

Measure	Zonisamide 100 mg Tablet n=29 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=25 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
The Mean Percent Change From Baseline in Simple Partial (SP) Seizure Frequency	-49.14 Percent Change Standard Deviation 62.06	56.03 Percent Change Standard Deviation 318.43

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: FAS Population. Secondary generalization patients

The mean percent change in seizure frequency of SGS from baseline during the fixed-dose phase.

Outcome measures

Measure	Zonisamide 100 mg Tablet n=36 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=42 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
The Mean Percent Change From Baseline in Partial Seizures With Secondary Generalization (SGS)	-53.2 Percent Change Standard Deviation 54.81	-4.08 Percent Change Standard Deviation 178.66

SECONDARY outcome

Timeframe: Baseline and 16 weeks

Population: FAS Population

Responder rate is defined as percentage of participants with >=50% reduction in seizure frequency from baseline.

Outcome measures

Measure	Zonisamide 100 mg Tablet n=111 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=106 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Responder Rate	48.6 Percentage of Participants	34.9 Percentage of Participants

SECONDARY outcome

Timeframe: 12 weeks

Population: FAS Population

Mean number of seizure free days per 28 day period during fixed dose phase

Outcome measures

Measure	Zonisamide 100 mg Tablet n=111 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=106 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Mean Number of Seizure Free Days	22.31 Days Standard Deviation 6.14	21.43 Days Standard Deviation 7.07

SECONDARY outcome

Timeframe: 16 weeks

Population: FAS Population

Outcome measures

Measure	Zonisamide 100 mg Tablet n=111 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=106 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Mean Percentage of Change in Seizure Free Days	79.69 Percent Change Standard Deviation 21.93	76.52 Percent Change Standard Deviation 25.26

SECONDARY outcome

Timeframe: 16 weeks

Population: FAS Population

Mean time to first seizure during fixed dose phase

Outcome measures

Measure	Zonisamide 100 mg Tablet n=111 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=106 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Mean Time to First Seizure (Days)	22.31 Days Standard Deviation 6.14	21.43 Days Standard Deviation 7.07

SECONDARY outcome

Timeframe: 16 weeks

Population: FAS Population

Percentage of seizure-free participants during fixed-dose phase

Outcome measures

Measure	Zonisamide 100 mg Tablet n=111 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=106 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Percentage of Seizure-free Participants During Fixed-dose Phase	1.8 Percentage of Participants	2.8 Percentage of Participants

SECONDARY outcome

Timeframe: 16 weeks

Population: FAS Population

Number of Participants who dropped out of the study. In the Study drop-out rate is defined as number of participants.

Outcome measures

Measure	Zonisamide 100 mg Tablet n=111 Participants Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=106 Participants Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Drop - Out Rate	4 Number of Participants	6 Number of Participants

Adverse Events

Zonisamide 100 mg Tablet

Serious events: 0 serious events

Other events: 95 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Zonisamide 100 mg Tablet n=120 participants at risk Patients entered a 4-week titration period, during which zonisamide dosing began at 100 mg/day for the first 2 weeks, increased to 200 mg/day for the 3rd week, and to 300 mg/day for the 4th week, reaching 300 mg/d at the end of the titration period. 300 mg/d was the target dose in the titration period and must be reached. Dose increment was continued to 400 mg/d if this was tolerated by the patient.	Placebo n=118 participants at risk Patients in placebo group were titrated with placebo in the same way as in zonisamide group.
Nervous system disorders Headache	10.8% 13/120 • Number of events 16 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	5.1% 6/118 • Number of events 8 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Nervous system disorders Dizziness	10.0% 12/120 • Number of events 15 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	11.0% 13/118 • Number of events 16 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Nervous system disorders Memory impairment	6.7% 8/120 • Number of events 8 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	0.85% 1/118 • Number of events 1 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Investigations White blood cell count decreased	8.3% 10/120 • Number of events 10 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	3.4% 4/118 • Number of events 4 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Investigations Platelet count decreased	5.8% 7/120 • Number of events 7 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	3.4% 4/118 • Number of events 4 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Investigations Weight decreased	5.0% 6/120 • Number of events 6 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	3.4% 4/118 • Number of events 4 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Psychiatric disorders somnolence	12.5% 15/120 • Number of events 18 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	14.4% 17/118 • Number of events 18 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Gastrointestinal disorders nausea	10.8% 13/120 • Number of events 14 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	5.9% 7/118 • Number of events 7 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Gastrointestinal disorders Abdominal distention	5.0% 6/120 • Number of events 6 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	0.85% 1/118 • Number of events 1 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Metabolism and nutrition disorders anorexia	18.3% 22/120 • Number of events 22 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	5.1% 6/118 • Number of events 7 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	10.8% 13/120 • Number of events 17 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.	14.4% 17/118 • Number of events 22 Placebo group has 2 fewer subjects - consent withdrawn 1 and lost to follow up 1.

Additional Information

Takao Ishii, Asia regulatory affairs

Eisai Co., Ltd.

Phone: 81-3-3817-3914

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place