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

Phase 4

Terminated

• Conditions: Epilepsy
• Interventions: Drug: Zonisamide at targeted daily doses of 100-500 mg/day; Drug: Placebo administered to match targeted daily doses of 100-500 mg/day

• Registration Number: NCT01546688
• Lead Sponsor: Eisai Limited

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2008-11
• Primary Completion: 2010-11
• Study Completion: 2011-08
• Study First Submitted: 2012-03-02
• Study First Submitted QC: 2012-03-02
• Study First Posted: 2012-03-07
• Results First Submitted: 2012-11-12
• Results First Submitted QC: 2013-01-02
• Results First Posted: 2013-02-06
• Status Verified: 2015-11
• Last Update Submitted: 2016-01-06
• Last Update Posted: 2016-01-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 41

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Zonisamide at targeted daily doses of 100-500 mg/day	Zonisamide at targeted daily doses of 100-500 mg/day	-
Placebo administered to match daily doses of 100-500 mg/day	Placebo administered to match targeted daily doses of 100-500 mg/day	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in CVST of the FePsy Test (Mean Reaction Time) by Visit During Titration and Maintenance Period	Baseline, Week 4, Week 8, Week 12, Week 16	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	Baseline, Week 4, Week 8, Week 12, Week 16	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

Name	Time	Method
Percent Change in Seizure Frequency From Baseline to the Last 28 Days of the Maintenance Period	Baseline and Month 4	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	Baseline and Month 4	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.

Trial Locations

Locations (36)

Asklepiosklinik Barmbek; 🇩🇪 Hamburg, Germany

Georg-August-Universiat Gottingen; 🇩🇪 Gottingen, Germany

Clinical Research Hamburg; 🇩🇪 Hamburg, Germany

ZNS Hamburg; 🇩🇪 Hamburg, Germany

Universitaet Giessen / Marburg; 🇩🇪 Marburg, Germany

Neurologische; 🇩🇪 Siegen, Germany

Dipartimento di Neuroscienze - Universita Federico II; 🇮🇹 Napoli, Italy

B-A-Z County Hospital - Szuleszet-Nogyogyaszat; 🇭🇺 Miskolc, Hungary

Oddzia Neurologiczny, Wojewdzki Szpital Specjalistyczny; 🇵🇱 Olsztyn, Poland

Synexus Magyarorszag Kft.; 🇭🇺 Budapest, Hungary

Epilepsie-Zentrum; 🇨🇭 Zurich, Switzerland

Semmelweis University - Neurology Dept.; 🇭🇺 Budapest, Hungary

Wielospecjalistyczna Lecznica 'Zycie'; 🇵🇱 Warszawa, Poland

NZOZ Centrum Medyczne HCP; 🇵🇱 Pozna, Poland

Centro per la Diagnosi e Cura dell'epilessia - Policlinico Universitario di Messina; 🇮🇹 Pavia, Italy

County Hospital Kecskemet; 🇭🇺 Keskemet, Hungary

Dip.to Scienze Neurologiche - III Clinica Neurologica; 🇮🇹 Roma, Italy

S.C. Neurologia - AO "G.Brotzu"; 🇮🇹 Cagliari, Italy

Klinik und Polyklinik fur Epileptologie; 🇩🇪 Bonn, Germany

Sopron Medical SMO; 🇭🇺 Sopron, Hungary

County Hospital of Zala; 🇭🇺 Zalaegerszeg, Hungary

Przych. Specj. I chorob Zaw. Wsi Instytut Medyc. Wsi im. W. Chodzki; 🇵🇱 Lublin, Poland

National Institute of Neurosurgery; 🇭🇺 Budapest, Hungary

Centro Epilessia - Istituto Neurologico "Fondazione C. Mondino"; 🇮🇹 Pavia, Italy

County Hospital of Tolna; 🇭🇺 Szeksz?rd, Hungary

Dip. Di neuroscienze - Centro Epilessie - Osp. Careggi; 🇮🇹 Firenze, Italy

Universita di Torino - Dipt. Neuroscienze; 🇮🇹 Torino, Italy

Medisch Centrum Haaglanden - Lokatie Westeinde; 🇳🇱 VA Den Haag, Netherlands

Specjalistyczny Zaklad Opieki Zdrowotnej 'KONSYLIUM'; 🇵🇱 Kalisz, Poland

Specjalistyczna Praktyka Lekarska; 🇵🇱 Katowice, Poland

NZOZ Centermed Gabinety ?lnolekarskie; 🇵🇱 Leszno, Poland

Clinical Investigation Unit; Inselspital; 🇨🇭 Bern, Switzerland

University Hospital of North Staffordshire; 🇬🇧 Stoke-on-Trent, United Kingdom

The Royal Cornwall Hospital; 🇬🇧 Truro, United Kingdom

Whipps Cross university Hospital; 🇬🇧 London, United Kingdom

Spitalzentrum Biel; 🇨🇭 Biel, Switzerland