Back to resultsA Study to Evaluate the Safety and Tolerability and Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures
Primary Purpose
Epilepsy
Status
Terminated
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Zonisamide at targeted daily doses of 100-500 mg/day
Placebo administered to match targeted daily doses of 100-500 mg/day
Sponsored by
About this trial
This is an interventional treatment trial for Epilepsy
Eligibility Criteria
Key Inclusion Criteria:
- Capable of maintaining a seizure daily diary or who have access to a caregiver who is prepared to complete this on the patient's behalf.
- Able to complete the questionnaires used in this study.
- Localization related epilepsy, with simple and/or complex partial seizures with or without secondary generalized seizures as defined by the International League Against Epilepsy (ILAE) criteria.
- Have at least one well documented seizure in the 4 weeks preceding the Randomisation Visit (Visit 2) and are deemed to require additional AED medication.
- Receiving at least one, but not more than two other marketed AEDs as concomitant medication, and the dosage should be stable for at least four weeks before the Screening Visit.
Key Exclusion Criteria:
- Seizures attributed to metabolic causes (e.g., electrolyte disturbances, hyperglycaemia).
- Seizures which could be attributed to use of a drug.
- Presence of primary generalised epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome.
- A history of eating disorders or a body weight below 40 kg.
- A history of blood dyscrasias.
- A history of renal stones or having risk factors for nephrolithiasis such as a family history of nephrolithiasis or hypercalciuria.
- An increased risk factor for rhabdomyolysis such as uncontrolled hypothyroidism, personal or family history of muscle disorders.
- Taking concomitant medication associated with nephrolithiasis and medications increasing the risk of rhabdomyolysis.
- Taking rifampicin or drugs with anticholinergic effects.
- Taking carbonic anhydrase inhibitors or topiramate.
- A history of pancreatitis.
- A history of Stevens Johnson Syndrome.
- Elevated levels of serum creatinine >165 Umol, or known severe hepatic impairment to the extent that the protocol dose titration schedule cannot be followed.
Sites / Locations
- Klinik und Polyklinik fur Epileptologie
- Georg-August-Universiat Gottingen
- Asklepiosklinik Barmbek
- Clinical Research Hamburg
- ZNS Hamburg
- Universitaet Giessen / Marburg
- Neurologische
- Semmelweis University - Neurology Dept.
- Synexus Magyarorszag Kft.
- National Institute of Neurosurgery
- County Hospital Kecskemet
- B-A-Z County Hospital - Szuleszet-Nogyogyaszat
- Sopron Medical SMO
- County Hospital of Tolna
- County Hospital of Zala
- S.C. Neurologia - AO "G.Brotzu"
- Dip. Di neuroscienze - Centro Epilessie - Osp. Careggi
- Dipartimento di Neuroscienze - Universita Federico II
- Centro Epilessia - Istituto Neurologico "Fondazione C. Mondino"
- Centro per la Diagnosi e Cura dell'epilessia - Policlinico Universitario di Messina
- Dip.to Scienze Neurologiche - III Clinica Neurologica
- Universita di Torino - Dipt. Neuroscienze
- Medisch Centrum Haaglanden - Lokatie Westeinde
- Specjalistyczny Zaklad Opieki Zdrowotnej 'KONSYLIUM'
- Specjalistyczna Praktyka Lekarska
- NZOZ Centermed Gabinety ?lnolekarskie
- Przych. Specj. I chorob Zaw. Wsi Instytut Medyc. Wsi im. W. Chodzki
- Oddzia Neurologiczny, Wojewdzki Szpital Specjalistyczny
- NZOZ Centrum Medyczne HCP
- Wielospecjalistyczna Lecznica 'Zycie'
- Clinical Investigation Unit; Inselspital
- Spitalzentrum Biel
- Epilepsie-Zentrum
- Whipps Cross university Hospital
- University Hospital of North Staffordshire
- The Royal Cornwall Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Zonisamide at targeted daily doses of 100-500 mg/day
Placebo administered to match daily doses of 100-500 mg/day
Arm Description
Outcomes
Primary Outcome Measures
Change From Baseline in CVST of the FePsy Test (Mean Reaction Time) by Visit During Titration and Maintenance Period
The Computer Visual Search Task (CVST) of the Ferrum Psyche (FePsy)measured cognition. A decrease from Baseline (negative change value) signifies an improvement in the mean reaction time of CVST.
Change From Baseline in Bond and Lader Visual Analogue Scale (VAS) Mood Sub-Scores for Sedation by Visit During Titration and Maintenance Period
The Bond-Lader mood rating scale measured sedation, with scores ranging from 0 to 100. A high score reflects a high level of sedation.
Secondary Outcome Measures
Percent Change in Seizure Frequency From Baseline to the Last 28 Days of the Maintenance Period
Seizure frequency was assessed by a seizure diary, maintained daily from Baseline, in which the subject recorded the occurrence of any seizure.
Percentage of Responders During Last 28 Days of Maintenance Period
Seizure frequency was assessed by a seizure diary, maintained daily from Baseline, in which the subject recorded the occurrence of any seizure. A responder is a subject who had at least a 50 percent or greater reduction in the seizure frequency of all seizures during the last 28 days of the Maintenance Period compared to the Baseline Period seizure frequency. Due to the exploratory nature of the objective for efficacy and the truncated study size, analysis of efficacy was based on observed cases, without imputation for missing data. As a result, there are some variations in sample sizes for efficacy at different visits, depending on if particular efficacy variables were missing for particular visits.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01546688
Brief Title
A Study to Evaluate the Safety and Tolerability and Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures
Official Title
A Randomised, Double Blind, Placebo-controlled Study to Evaluate the Safety and Tolerability and to Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures
Study Type
Interventional
2. Study Status
Record Verification Date
November 2015
Overall Recruitment Status
Terminated
Study Start Date
November 2008 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
August 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eisai Limited
4. Oversight
5. Study Description
Brief Summary
A two arm, randomized, double-blind study comparing zonisamide with placebo. The zonisamide arm will consist of 100 subjects and the placebo arm of 50 subjects. Study medication will be administered as an add-on treatment to the subject's current 1 or 2 anti-epileptic (AEDs).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epilepsy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
41 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Zonisamide at targeted daily doses of 100-500 mg/day
Arm Type
Active Comparator
Arm Title
Placebo administered to match daily doses of 100-500 mg/day
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Zonisamide at targeted daily doses of 100-500 mg/day
Intervention Description
Each group received 2 doses a day (in the morning and evening) during the Titration Period, once a day (in the evening) or BID during the Maintenance Phase, comprising 25 mg, 50 mg, or 100 mg of ZNS capsules
Intervention Type
Drug
Intervention Name(s)
Placebo administered to match targeted daily doses of 100-500 mg/day
Intervention Description
matching placebo
Primary Outcome Measure Information:
Title
Change From Baseline in CVST of the FePsy Test (Mean Reaction Time) by Visit During Titration and Maintenance Period
Description
The Computer Visual Search Task (CVST) of the Ferrum Psyche (FePsy)measured cognition. A decrease from Baseline (negative change value) signifies an improvement in the mean reaction time of CVST.
Time Frame
Baseline, Week 4, Week 8, Week 12, Week 16
Title
Change From Baseline in Bond and Lader Visual Analogue Scale (VAS) Mood Sub-Scores for Sedation by Visit During Titration and Maintenance Period
Description
The Bond-Lader mood rating scale measured sedation, with scores ranging from 0 to 100. A high score reflects a high level of sedation.
Time Frame
Baseline, Week 4, Week 8, Week 12, Week 16
Secondary Outcome Measure Information:
Title
Percent Change in Seizure Frequency From Baseline to the Last 28 Days of the Maintenance Period
Description
Seizure frequency was assessed by a seizure diary, maintained daily from Baseline, in which the subject recorded the occurrence of any seizure.
Time Frame
Baseline and Month 4
Title
Percentage of Responders During Last 28 Days of Maintenance Period
Description
Seizure frequency was assessed by a seizure diary, maintained daily from Baseline, in which the subject recorded the occurrence of any seizure. A responder is a subject who had at least a 50 percent or greater reduction in the seizure frequency of all seizures during the last 28 days of the Maintenance Period compared to the Baseline Period seizure frequency. Due to the exploratory nature of the objective for efficacy and the truncated study size, analysis of efficacy was based on observed cases, without imputation for missing data. As a result, there are some variations in sample sizes for efficacy at different visits, depending on if particular efficacy variables were missing for particular visits.
Time Frame
Baseline and Month 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Capable of maintaining a seizure daily diary or who have access to a caregiver who is prepared to complete this on the patient's behalf.
Able to complete the questionnaires used in this study.
Localization related epilepsy, with simple and/or complex partial seizures with or without secondary generalized seizures as defined by the International League Against Epilepsy (ILAE) criteria.
Have at least one well documented seizure in the 4 weeks preceding the Randomisation Visit (Visit 2) and are deemed to require additional AED medication.
Receiving at least one, but not more than two other marketed AEDs as concomitant medication, and the dosage should be stable for at least four weeks before the Screening Visit.
Key Exclusion Criteria:
Seizures attributed to metabolic causes (e.g., electrolyte disturbances, hyperglycaemia).
Seizures which could be attributed to use of a drug.
Presence of primary generalised epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome.
A history of eating disorders or a body weight below 40 kg.
A history of blood dyscrasias.
A history of renal stones or having risk factors for nephrolithiasis such as a family history of nephrolithiasis or hypercalciuria.
An increased risk factor for rhabdomyolysis such as uncontrolled hypothyroidism, personal or family history of muscle disorders.
Taking concomitant medication associated with nephrolithiasis and medications increasing the risk of rhabdomyolysis.
Taking rifampicin or drugs with anticholinergic effects.
Taking carbonic anhydrase inhibitors or topiramate.
A history of pancreatitis.
A history of Stevens Johnson Syndrome.
Elevated levels of serum creatinine >165 Umol, or known severe hepatic impairment to the extent that the protocol dose titration schedule cannot be followed.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joanna Segieth
Organizational Affiliation
Eisai Limited
Official's Role
Study Director
Facility Information:
Facility Name
Klinik und Polyklinik fur Epileptologie
City
Bonn
Country
Germany
Facility Name
Georg-August-Universiat Gottingen
City
Gottingen
Country
Germany
Facility Name
Asklepiosklinik Barmbek
City
Hamburg
Country
Germany
Facility Name
Clinical Research Hamburg
City
Hamburg
Country
Germany
Facility Name
ZNS Hamburg
City
Hamburg
Country
Germany
Facility Name
Universitaet Giessen / Marburg
City
Marburg
Country
Germany
Facility Name
Neurologische
City
Siegen
Country
Germany
Facility Name
Semmelweis University - Neurology Dept.
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Synexus Magyarorszag Kft.
City
Budapest
ZIP/Postal Code
11036
Country
Hungary
Facility Name
National Institute of Neurosurgery
City
Budapest
ZIP/Postal Code
1145
Country
Hungary
Facility Name
County Hospital Kecskemet
City
Keskemet
ZIP/Postal Code
6000
Country
Hungary
Facility Name
B-A-Z County Hospital - Szuleszet-Nogyogyaszat
City
Miskolc
ZIP/Postal Code
3501
Country
Hungary
Facility Name
Sopron Medical SMO
City
Sopron
ZIP/Postal Code
9400
Country
Hungary
Facility Name
County Hospital of Tolna
City
Szeksz?rd
ZIP/Postal Code
7100
Country
Hungary
Facility Name
County Hospital of Zala
City
Zalaegerszeg
ZIP/Postal Code
8900
Country
Hungary
Facility Name
S.C. Neurologia - AO "G.Brotzu"
City
Cagliari
ZIP/Postal Code
00134
Country
Italy
Facility Name
Dip. Di neuroscienze - Centro Epilessie - Osp. Careggi
City
Firenze
ZIP/Postal Code
50134
Country
Italy
Facility Name
Dipartimento di Neuroscienze - Universita Federico II
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Centro Epilessia - Istituto Neurologico "Fondazione C. Mondino"
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Centro per la Diagnosi e Cura dell'epilessia - Policlinico Universitario di Messina
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Facility Name
Dip.to Scienze Neurologiche - III Clinica Neurologica
City
Roma
ZIP/Postal Code
00185
Country
Italy
Facility Name
Universita di Torino - Dipt. Neuroscienze
City
Torino
ZIP/Postal Code
10126
Country
Italy
Facility Name
Medisch Centrum Haaglanden - Lokatie Westeinde
City
VA Den Haag
ZIP/Postal Code
2512
Country
Netherlands
Facility Name
Specjalistyczny Zaklad Opieki Zdrowotnej 'KONSYLIUM'
City
Kalisz
ZIP/Postal Code
62-800
Country
Poland
Facility Name
Specjalistyczna Praktyka Lekarska
City
Katowice
ZIP/Postal Code
40- 097
Country
Poland
Facility Name
NZOZ Centermed Gabinety ?lnolekarskie
City
Leszno
ZIP/Postal Code
64-100
Country
Poland
Facility Name
Przych. Specj. I chorob Zaw. Wsi Instytut Medyc. Wsi im. W. Chodzki
City
Lublin
ZIP/Postal Code
20-090
Country
Poland
Facility Name
Oddzia Neurologiczny, Wojewdzki Szpital Specjalistyczny
City
Olsztyn
ZIP/Postal Code
10-561
Country
Poland
Facility Name
NZOZ Centrum Medyczne HCP
City
Pozna
ZIP/Postal Code
61-489
Country
Poland
Facility Name
Wielospecjalistyczna Lecznica 'Zycie'
City
Warszawa
ZIP/Postal Code
03-464
Country
Poland
Facility Name
Clinical Investigation Unit; Inselspital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Spitalzentrum Biel
City
Biel
ZIP/Postal Code
2501
Country
Switzerland
Facility Name
Epilepsie-Zentrum
City
Zurich
ZIP/Postal Code
8008
Country
Switzerland
Facility Name
Whipps Cross university Hospital
City
London
ZIP/Postal Code
E11 1NR
Country
United Kingdom
Facility Name
University Hospital of North Staffordshire
City
Stoke-on-Trent
ZIP/Postal Code
ST4 7LN
Country
United Kingdom
Facility Name
The Royal Cornwall Hospital
City
Truro
ZIP/Postal Code
TR1 3LJ
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate the Safety and Tolerability and Explore the Efficacy of Zonisamide as add-on Therapy in Elderly Patients With Refractory Partial Seizures
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