Trial Outcomes & Findings for Efficacy and Safety of Adjunctive Zonisamide in Myoclonic Seizures Associated With Idiopathic Generalised Epilepsy (NCT NCT00693017)

Results Overview

The number of participants who were considered responders during the 12 week Maintenance Period (Week 4 to Week 16). A responder was defined as a participant with a decrease \>= 50% from baseline in the number of days with myoclonic seizures per 28 days (i.e. 28-day myoclonic seizure frequency in Period from Week 4 to the Week 16 visit compared to Week -8 to randomization at Week 0 \[Screening/ Baseline Period\]). Occurrence of seizures was documented in a seizure diary. The diary was dispensed at the Screening Visit and maintained by the participant (parent/caregiver) and reviewed at each following visit. The diary was completed daily. All seizures except myoclonic seizures were counted individually in the the diary. Due to early termination of the study by the Sponsor, no formal analyses were conducted.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

10 participants

Primary outcome timeframe

Baseline (Week -8 to Week 0) and Maintenance Period (Week 4 to Week 16)

Results posted on

2015-12-24

Participant Flow

This study was recruited at three study centers (1 in Australia and 2 in Hungary). A further 39 study centers in Europe and Australia were initiated. A total of 12 study sites in the following countries were not initiated; (2 in Finland), (3 in Czech Republic), and (7 in Ukraine) during the period of 04 June 2008 to 05 January 2009.

10 participants were screened for eligibility and six participants did not continue after the Screening Visit due to the Sponsor's decision to terminate the study. 4 participants were enrolled and treated during the study.

Participant milestones

Participant milestones
Measure	Zonisamide 50-400 mg capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)	Placebo 50-400 mg Zonisamide Placebo capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg Zonisamide Placebo daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg Zonisamide Placebo (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)
Overall Study STARTED	2	2
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Zonisamide 50-400 mg capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)	Placebo 50-400 mg Zonisamide Placebo capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg Zonisamide Placebo daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg Zonisamide Placebo (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)
Overall Study Sponsor Decision	2	1
Overall Study Death	0	1

Baseline Characteristics

Efficacy and Safety of Adjunctive Zonisamide in Myoclonic Seizures Associated With Idiopathic Generalised Epilepsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zonisamide n=2 Participants 50-400 mg capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)	Placebo n=2 Participants 50-400 mg Zonisamide Placebo capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg Zonisamide Placebo daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg Zonisamide Placebo (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)	Total n=4 Participants Total of all reporting groups
Age, Continuous	24.0 years STANDARD_DEVIATION 16.97 • n=5 Participants	33.5 years STANDARD_DEVIATION 23.33 • n=7 Participants	28.8 years STANDARD_DEVIATION 17.54 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Week -8 to Week 0) and Maintenance Period (Week 4 to Week 16)

The number of participants who were considered responders during the 12 week Maintenance Period (Week 4 to Week 16). A responder was defined as a participant with a decrease \>= 50% from baseline in the number of days with myoclonic seizures per 28 days (i.e. 28-day myoclonic seizure frequency in Period from Week 4 to the Week 16 visit compared to Week -8 to randomization at Week 0 \[Screening/ Baseline Period\]). Occurrence of seizures was documented in a seizure diary. The diary was dispensed at the Screening Visit and maintained by the participant (parent/caregiver) and reviewed at each following visit. The diary was completed daily. All seizures except myoclonic seizures were counted individually in the the diary. Due to early termination of the study by the Sponsor, no formal analyses were conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and up to 16 weeks

Percentage Change from Baseline in the monthly number of days with myoclonic seizures was assessed both for the Maintenance Period alone (Week 4 to Week 16) and for the entire double-blind treatment period (Week 0 to Week 16). Due to early termination of the study by the Sponsor, no formal analyses were conducted.

Outcome measures

Outcome data not reported

Adverse Events

Zonisamide

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Zonisamide n=2 participants at risk 50-400 mg capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)	Placebo n=2 participants at risk 50-400 mg Zonisamide Placebo capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg Zonisamide Placebo daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg Zonisamide Placebo (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)
General disorders Sudden unexplained death in epilepsy	0.00% 0/2	50.0% 1/2

Other adverse events

Other adverse events
Measure	Zonisamide n=2 participants at risk 50-400 mg capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)	Placebo n=2 participants at risk 50-400 mg Zonisamide Placebo capsules once daily in the evening orally. Maximum study duration 28 weeks comprising: Baseline Period (Week -8 to Week 0): no treatment Titration Period (Week 0 to Week 4): 50 mg Zonisamide Placebo daily titrated weekly until 300 mg was reached by Week 4 Maintenance Period (Week 4 to Week 16) 400 mg Zonisamide Placebo (or 350 mg in the event of dose limiting adverse events) Down Titration Period (4 Weeks)
Eye disorders Vision blurred	50.0% 1/2	50.0% 1/2
Gastrointestinal disorders Vomiting	50.0% 1/2	0.00% 0/2
Nervous system disorders Dizziness	50.0% 1/2	0.00% 0/2
Nervous system disorders Headache	0.00% 0/2	50.0% 1/2
Nervous system disorders Somnolence	50.0% 1/2	0.00% 0/2
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/2	50.0% 1/2

Additional Information

Antonio Laurenza, MD, Executive Director

Eisai Inc

Phone: 1 201 949-4157

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place