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

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01546688
• Other study ID #: E2090-E044-402
• Secondary ID: 2006-002516-10
• Status: Terminated
• Phase: Phase 4
• First received: March 2, 2012
• Last updated: January 6, 2016
• Start date: November 2008
• Est. completion date: August 2011

Study information

• Verified date: November 2015
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: European Union: European Medicines Agency
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 41
• Est. completion date: August 2011
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years and older

Eligibility

Key Inclusion Criteria:

1. 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.

2. Able to complete the questionnaires used in this study.

3. 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.

4. 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.

5. 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:

1. Seizures attributed to metabolic causes (e.g., electrolyte disturbances, hyperglycaemia).

2. Seizures which could be attributed to use of a drug.

3. Presence of primary generalised epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox-Gastaut syndrome.

4. A history of eating disorders or a body weight below 40 kg.

5. A history of blood dyscrasias.

6. A history of renal stones or having risk factors for nephrolithiasis such as a family history of nephrolithiasis or hypercalciuria.

7. An increased risk factor for rhabdomyolysis such as uncontrolled hypothyroidism, personal or family history of muscle disorders.

8. Taking concomitant medication associated with nephrolithiasis and medications increasing the risk of rhabdomyolysis.

9. Taking rifampicin or drugs with anticholinergic effects.

10. Taking carbonic anhydrase inhibitors or topiramate.

11. A history of pancreatitis.

12. A history of Stevens Johnson Syndrome.

13. Elevated levels of serum creatinine >165 Umol, or known severe hepatic impairment to the extent that the protocol dose titration schedule cannot be followed.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Zonisamide at targeted daily doses of 100-500 mg/day
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
• Placebo administered to match targeted daily doses of 100-500 mg/day
matching placebo

Locations

Country	Name	City	State
Germany	Klinik und Polyklinik fur Epileptologie	Bonn
Germany	Georg-August-Universiat Gottingen	Gottingen
Germany	Asklepiosklinik Barmbek	Hamburg
Germany	Clinical Research Hamburg	Hamburg
Germany	ZNS Hamburg	Hamburg
Germany	Universitaet Giessen / Marburg	Marburg
Germany	Neurologische	Siegen
Hungary	National Institute of Neurosurgery	Budapest
Hungary	Semmelweis University - Neurology Dept.	Budapest
Hungary	Synexus Magyarorszag Kft.	Budapest
Hungary	County Hospital Kecskemet	Keskemet
Hungary	B-A-Z County Hospital - Szuleszet-Nogyogyaszat	Miskolc
Hungary	Sopron Medical SMO	Sopron
Hungary	County Hospital of Tolna	Szeksz?rd
Hungary	County Hospital of Zala	Zalaegerszeg
Italy	S.C. Neurologia - AO "G.Brotzu"	Cagliari
Italy	Dip. Di neuroscienze - Centro Epilessie - Osp. Careggi	Firenze
Italy	Dipartimento di Neuroscienze - Universita Federico II	Napoli
Italy	Centro Epilessia - Istituto Neurologico "Fondazione C. Mondino"	Pavia
Italy	Centro per la Diagnosi e Cura dell'epilessia - Policlinico Universitario di Messina	Pavia
Italy	Dip.to Scienze Neurologiche - III Clinica Neurologica	Roma
Italy	Universita di Torino - Dipt. Neuroscienze	Torino
Netherlands	Medisch Centrum Haaglanden - Lokatie Westeinde	VA Den Haag
Poland	Specjalistyczny Zaklad Opieki Zdrowotnej 'KONSYLIUM'	Kalisz
Poland	Specjalistyczna Praktyka Lekarska	Katowice
Poland	NZOZ Centermed Gabinety ?lnolekarskie	Leszno
Poland	Przych. Specj. I chorob Zaw. Wsi Instytut Medyc. Wsi im. W. Chodzki	Lublin
Poland	Oddzia Neurologiczny, Wojewdzki Szpital Specjalistyczny	Olsztyn
Poland	NZOZ Centrum Medyczne HCP	Pozna
Poland	Wielospecjalistyczna Lecznica 'Zycie'	Warszawa
Switzerland	Clinical Investigation Unit; Inselspital	Bern
Switzerland	Spitalzentrum Biel	Biel
Switzerland	Epilepsie-Zentrum	Zurich
United Kingdom	Whipps Cross university Hospital	London
United Kingdom	University Hospital of North Staffordshire	Stoke-on-Trent
United Kingdom	The Royal Cornwall Hospital	Truro

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Limited

Countries where clinical trial is conducted

Germany,  Hungary,  Italy,  Netherlands,  Poland,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Week 4, Week 8, Week 12, Week 16	No
Primary	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.	Baseline, Week 4, Week 8, Week 12, Week 16	No
Secondary	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.	Baseline and Month 4	No
Secondary	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.	Baseline and Month 4	No