Trial Outcomes & Findings for Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Study) (NCT NCT00566254)

NCT ID: NCT00566254

Last Updated: 2013-05-13

Results Overview

A participant with a decrease from baseline in seizure frequency of =50 % was considered a responder. Participants' parent or guardian maintained a seizure diary recording the date, number, and type of seizures the subject had. The primary analysis assessed the percent of responders in the Maintenance Period (28- day seizure frequency in Week 8 to Week 20 compared to Week -8 to Week 0 at Last Observation Carried Forward (LOCF)). Seizure frequency of simple partial, complex partial, and partial seizures with secondary generalization were assessed.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 207 participants
• Primary outcome timeframe: Baseline (Week -8 to Week 0), and Week 8 to Week 20
• Results posted on: 2013-05-13

Participant Flow

Participant milestones

Measure	Placebo Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.
Overall Study STARTED	100	107
Overall Study COMPLETED	90	93
Overall Study NOT COMPLETED	10	14

Reasons for withdrawal

Measure	Placebo Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.
Overall Study Adverse Event	3	1
Overall Study Protocol Violation	1	3
Overall Study Withdrawal by Subject	1	2
Overall Study Lack of Efficacy	5	6
Overall Study Other	0	2

Baseline Characteristics

Efficacy and Safety of Adjunctive Zonisamide in Paediatric Partial Onset Seizures (CATZ Study)

Baseline characteristics by cohort

Measure	Placebo n=100 Participants Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide n=107 Participants Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Total n=207 Participants Total of all reporting groups
Age, Customized 6-11 Years Old	55 Participants n=5 Participants	55 Participants n=7 Participants	110 Participants n=5 Participants
Age, Customized 12-17 Years Old	45 Participants n=5 Participants	52 Participants n=7 Participants	97 Participants n=5 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	54 Participants n=7 Participants	99 Participants n=5 Participants
Sex: Female, Male Male	55 Participants n=5 Participants	53 Participants n=7 Participants	108 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Week -8 to Week 0), and Week 8 to Week 20

Population: The Intent to Treat (ITT)Population was defined as the group of randomized subjects who received at least one does of doubleblind study medication

A participant with a decrease from baseline in seizure frequency of =50 % was considered a responder. Participants' parent or guardian maintained a seizure diary recording the date, number, and type of seizures the subject had. The primary analysis assessed the percent of responders in the Maintenance Period (28- day seizure frequency in Week 8 to Week 20 compared to Week -8 to Week 0 at Last Observation Carried Forward (LOCF)). Seizure frequency of simple partial, complex partial, and partial seizures with secondary generalization were assessed.

Outcome measures

Measure	Placebo n=100 Participants Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide n=107 Participants Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.
Percentage of Participants With a Decrease From Baseline in 28-day Seizure Frequency of =50%(Responder) in the Maintenance Period(LOCF)	31 Percentage of Participants	50 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Week -8 to Week 0) and Week 8 to Week 20

Population: ITT Population

Participants' parent or guardian maintained a seizure diary recording the date, number,and type of seizures the subject had. Seizure frequency of simple partial,complex partial,and partial seizures with secondary generalization were assessed.

Outcome measures

Measure	Placebo n=100 Participants Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide n=107 Participants Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.
Median Percent Change From Baseline in the 28-day Seizure Frequency During the Maintenance Period (LOCF)	-24.5 Percentage Change in Seizure Frequency Interval -100.0 to 1055.0	-50.0 Percentage Change in Seizure Frequency Interval -100.0 to 374.0

SECONDARY outcome

Timeframe: Baseline (Week -8 to Week 0) and Week 8 to Week 20

Population: ITT Population

Participants' parent or guardian maintained a seizure diary recording the date, number, and type of seizures the subject had. Seizure frequency of simple partial, complex partial,and partial seizures with secondary generalization were assessed.

Outcome measures

Measure	Placebo n=100 Participants Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide n=107 Participants Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.
Percent of Participants With =50% to < 75% and = 75% Decrease From Baseline in 28-day Seizure Frequency During the Maintenance Period(LOCF) Greater than or equal to 75% decrease	12.0 Percentage of Participants	27.1 Percentage of Participants
Percent of Participants With =50% to < 75% and = 75% Decrease From Baseline in 28-day Seizure Frequency During the Maintenance Period(LOCF) Great than or equal to50% to less than75% decrease	19.0 Percentage of Participants	23.4 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Week -8 to Week 0) and Week 8 to Week 20

Population: ITT Population

Participants' parent or guardian maintained a seizure diary recording the date, number, and type of seizures the subject had. Seizure frequency of simple partial, complex partial, and partial seizures with secondary generalization were assessed.

Outcome measures

Measure	Placebo n=100 Participants Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide n=107 Participants Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.
Percent of Participants With =25% and =100% Increase From Baseline in 28-day Seizure Frequency During the Maintenance Period (LOCF) Greater than or equal to 25% increase	21.0 Percentage of Participants	10.0 Percentage of Participants
Percent of Participants With =25% and =100% Increase From Baseline in 28-day Seizure Frequency During the Maintenance Period (LOCF) Greater than or equal to 100% increase	9.0 Percentage of Participants	5.0 Percentage of Participants

Adverse Events

Placebo

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Zonisamide

Serious events: 4 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=100 participants at risk Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide n=107 participants at risk Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.
Nervous system disorders Complex partial seizures	1.0% 1/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.00% 0/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Nervous system disorders Somnolence	1.0% 1/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.00% 0/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Nervous system disorders Status epilepticus	0.00% 0/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.93% 1/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Gastrointestinal disorders Abdominal pain	0.00% 0/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.93% 1/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Gastrointestinal disorders Vomiting	1.0% 1/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.00% 0/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Hepatobiliary disorders Cholelithiasis	0.00% 0/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.93% 1/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Investigations Blood glucose decreased	0.00% 0/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.93% 1/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Investigations Weight decreased	0.00% 0/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.93% 1/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Metabolism and nutrition disorders Dehydration	0.00% 0/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	0.93% 1/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.

Other adverse events

Measure	Placebo n=100 participants at risk Participants had a starting dose of 1 mg/kg/day of placebo matching Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.	Zonisamide n=107 participants at risk Participants had a starting dose of 1 mg/kg/day of Zonisamide. Dose was titrated upwards with weekly dose increases until a dose of 8 mg/kg/day was reached at the end of the Titration Period (Week 8). Dose during the Maintenance Period remained unchanged from Week 8.
Infections and infestations Nasopharyngitis	9.0% 9/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	5.6% 6/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Nervous system disorders Headache	7.0% 7/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	6.5% 7/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Gastrointestinal disorders Abdominal pain upper	6.0% 6/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	1.9% 2/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.
Metabolism and nutrition disorders Decreased appetite	4.0% 4/100 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.	6.5% 7/107 • From the time the subject signed the informed consent form through the Final Visit/Early Termination Visit and for 15 days following study drug discontinuation. Adverse events (AEs) were assessed at clinical visits based on the subject's diary, vitals, weight, physical examination, neurological exam, and laboratory evaluations; and by telephone interviews/contact.

Additional Information

Eisai Inc.

Eisai Call Center

Phone: 888-422-4743

Results disclosure agreements

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