Trial Outcomes & Findings for Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures (NCT NCT00692003)
NCT ID: NCT00692003
Last Updated: 2017-03-14
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 from baseline in Primary Generalised Tonic-Clonic Seizures (PGTCS) frequency of \>= 50% (i.e. 28-day PGTC seizure frequency in the period from Week 4 to the Week 16 visit compared to Week -8/-4 to randomization at Week 0). Each participant's response to treatment was assessed on the basis of their seizure diaries. The diary was dispensed at the Screening Visit and maintained by the participant (parent/caregiver) through out the titration and maintenance treatment periods until the Early termination Visit at Week 16. Due to early termination of the study by the Sponsor, no formal analyses were conducted.
TERMINATED
PHASE3
21 participants
Baseline (Week -8/-4 to Week 0) and Maintenance Phase (Week 4 to Week 16)
2017-03-14
Participant Flow
This study was recruited at 6 centers (3 in Romania and 1 in Australia, Hungary, and Lithuania) during the period of 01 August 2008 to 28 January 2009.
Twenty-one subjects were screened and 14 participants did not continue the study after screening. Seven participants entered the study but 1 participant did not receive any treatment. Consequently, 6 participants were enrolled and treated during the study. None of the 6 subjects completed treatment \& all discontinued due to the Sponsor's decision.
Participant milestones
| Measure |
Zonisamide
25-400 mg capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) \<12 years old: 1 mg/kg;
\>= 12 years old: 50 mg daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)
|
Placebo
25-400 mg Zonisamide Placebo capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) \<12 years old: 1 mg/kg Zonisamide Placebo;
\>= 12 years old: 50 mg Zonisamide Placebo capsules daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
1
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
5
|
1
|
Reasons for withdrawal
| Measure |
Zonisamide
25-400 mg capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) \<12 years old: 1 mg/kg;
\>= 12 years old: 50 mg daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)
|
Placebo
25-400 mg Zonisamide Placebo capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) \<12 years old: 1 mg/kg Zonisamide Placebo;
\>= 12 years old: 50 mg Zonisamide Placebo capsules daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)
|
|---|---|---|
|
Overall Study
Sponsor Decision
|
5
|
1
|
Baseline Characteristics
Adjunctive Zonisamide in Primary Generalised Tonic Clonic Seizures
Baseline characteristics by cohort
| Measure |
Zonisamide
n=5 Participants
25-400 mg capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) \<12 years old: 1 mg/kg;
\>= 12 years old: 50 mg daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained(4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)
|
Placebo
n=1 Participants
25-400 mg Zonisamide Placebo capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) \<12 years old: 1 mg/kg Zonisamide Placebo; \>= 12 years old: 50 mg Zonisamide Placebo capsules daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)
|
Total
n=6 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
38.4 years
STANDARD_DEVIATION 18.66 • n=5 Participants
|
27.0 years
STANDARD_DEVIATION NA • n=7 Participants
|
36.5 years
STANDARD_DEVIATION 17.33 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Week -8/-4 to Week 0) and Maintenance Phase (Week 4 to Week 16)Population: Due to early termination of the study by the Sponsor, no formal analyses were conducted.
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 from baseline in Primary Generalised Tonic-Clonic Seizures (PGTCS) frequency of \>= 50% (i.e. 28-day PGTC seizure frequency in the period from Week 4 to the Week 16 visit compared to Week -8/-4 to randomization at Week 0). Each participant's response to treatment was assessed on the basis of their seizure diaries. The diary was dispensed at the Screening Visit and maintained by the participant (parent/caregiver) through out the titration and maintenance treatment periods until the Early termination Visit at Week 16. 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 weeksPopulation: Due to early termination of the study by the Sponsor, no formal analyses were conducted.
Absolute Change from Baseline in 28-day PGTC Seizure Frequency 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
Placebo
Zonisamide
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=1 participants at risk
25-400 mg Zonisamide Placebo capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) \<12 years old: 1 mg/kg Zonisamide Placebo; \>= 12 years old: 50 mg Zonisamide Placebo capsules daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)
|
Zonisamide
n=5 participants at risk
25-400 mg capsules orally once daily in the evening.
Maximum study duration of 28 weeks comprising:
Baseline Period (Week-8/-4 to Week 0) no treatment
Titration Period (Week 0 to Week 4) \<12 years old: 1 mg/kg; \>= 12 years old: 50 mg daily titrated weekly until a dose of 5 mg/kg or 300 mg was reached by Week 4
Maintenance Period (Week 4 to Week 16) dose from Week 4 to be maintained (4 mg/kg or 200 mg in the event of dose limiting adverse events)
Down Titration Period (4 weeks)
|
|---|---|---|
|
General disorders
Fatigue
|
0.00%
0/1 • Adverse events were collected for approximately 3 months
|
20.0%
1/5 • Adverse events were collected for approximately 3 months
|
|
General disorders
Gait disturbance
|
0.00%
0/1 • Adverse events were collected for approximately 3 months
|
20.0%
1/5 • Adverse events were collected for approximately 3 months
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/1 • Adverse events were collected for approximately 3 months
|
20.0%
1/5 • Adverse events were collected for approximately 3 months
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/1 • Adverse events were collected for approximately 3 months
|
20.0%
1/5 • Adverse events were collected for approximately 3 months
|
|
Nervous system disorders
Dizziness
|
0.00%
0/1 • Adverse events were collected for approximately 3 months
|
20.0%
1/5 • Adverse events were collected for approximately 3 months
|
|
Nervous system disorders
Postictal headache
|
0.00%
0/1 • Adverse events were collected for approximately 3 months
|
20.0%
1/5 • Adverse events were collected for approximately 3 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place