Assessing The Long-Term Safety And To Explore The Long-Term Efficacy Of Zonisamide As Monotherapy In Newly Diagnosed Partial Seizures

Epilepsy Clinical Trial

Official title:

A Randomized, Double-Blind Extension Study To Assess The Long-Term Safety And To Explore The Long-Term Efficacy Of Zonisamide As Monotherapy In Newly Diagnosed Partial Seizures

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00848549
• Other study ID #: E2090-E044-314
• Secondary ID: 2008-001159-23
• Status: Completed
• Phase: Phase 3
• First received: February 19, 2009
• Last updated: December 21, 2015
• Start date: October 2008
• Est. completion date: November 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

The purpose of this study is to assess the long-term safety and tolerability and to explore the long-term efficacy of zonisamide as monotherapy treatment in subjects with newly diagnosed partial seizures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: November 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 78 Years

Eligibility

Inclusion Criteria:

1. Subject has completed study E2090-E044-310.

2. Subject is able and willing to give written informed consent.

3. Female subjects without childbearing potential (two years post-menopausal, bilateral oophorectomy or tubal ligation, complete hysterectomy) are eligible. Female subjects of childbearing potential must be non-pregnant, non-lactating and abide by one of the following medically acceptable contraceptive measures: oral contraceptive pill, contraceptive injections, implants or patches, intrauterine device in place for at least three months, vasectomised partner or abstinence throughout the study and for one month after discontinuation of study medication. When the contraceptive pill is used, this should contain no less than 50 µg oestrogen.

4. The subject is able and willing to follow the investigational study procedures, maintain a seizure diary and report adverse events.

Exclusion Criteria:

1. Subject has a history of a significant or currently uncontrolled disease that will contraindicate the use of the study drugs or interfere with the conduct of this study and/or the assessment of safety and efficacy of the study drugs.

2. Subject has a body weight <40 kg.

3. Subject has a newly occurring progressive malignancy during study E2090-E044-310 (excluding a history of non-metastasized and adequately treated cutaneous squamous cell carcinoma).

4. Subject has developed a psychiatric illness or mood disorder requiring electro-convulsive or drug therapy within the previous 6 months and is considered uncontrolled; history of suicide attempt, alcohol or drug abuse, chronic treatment with benzodiazepines or barbiturates.

5. Subject is currently taking carbonic anhydrase inhibitors.

6. Subject developed pancreatitis, nephrolithiasis or hypercalcuria, clinically significant laboratory abnormalities, stroke or uncontrolled hypertension during study E2090-E044-310.

7. Subject is currently taking monoamine oxidase inhibitors (MAOIs) or any other excluded medications (see protocol section 9.9.3).

8. Subject has a history of allergy to carbamazepine or to zonisamide or to any of their ingredients or to sulphonamides.

9. Subject has developed a bone marrow depression, low platelet count or other blood dyscrasias.

Study Design

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

Related Conditions & MeSH terms

• Epilepsy

Intervention

Drug:
• Zonisamide
Subjects will start on the same dose that was achieved at the end of study E2090-E044-310. Maximum daily dose allowable is 500 mg; the minimum daily dose allowable is 200 mg. During the study, subjects will be titrated up or down depending on seizure-free status or intolerability/adverse events, respectively. Should a dose outside of the maximum be required the subject will be with drawn and gradually down titrated by 100 mg per week.
• Carbamazepine
Subjects will start on the same dose that was achieved at the end of study E2090-E044-310. Maximum daily dose allowable is 1200 mg; the minimum daily dose allowable is 400 mg. During the study, subjects will be titrated up or down depending on seizure-free status or intolerability/adverse events respectively. Should a dose outside of the maximum be required the subject will be with drawn and gradually down titrated by 200 mg per week.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Countries where clinical trial is conducted

Australia,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Italy,  Korea, Republic of,  Montenegro,  Poland,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Remaining in the Study at Each Visit	The retention rate is defined as the percentage of subjects remaining on the study at each visit, starting from the first dose of study drug in the extension phase.	At 3, 6, 9, 12, 15, 18, 21, 24, and 27 months	No
Secondary	Time to Drop-out Due to Lack of Efficacy	Lack of efficacy was if the subject had poor seizure control (defined as experiencing a seizure despite being on the maximum dose for = 2 weeks). The subject could withdraw at any time due to lack of efficacy.	Week 1 to Week 109 (in core study) and Month 1 to Month 27 (in extension study)	No
Secondary	Time to Drop-out Due to Adverse Event (AE)	Adverse events in study subjects included any change in the subject's condition.; This includes symptoms, physical findings, or clinical syndromes. All AEs that occurred after signing of informed consent through the last visit and for 15 days following study drug discontinuation were captured on the AE Case Report Form (CRF).	Week 1 to Week 109 (in base study) and Month 1 to Month 27 (in extension study)	No
Secondary	Percentage of Participants That Are Seizure Free for at Least 24 Month Consecutive Period in the Base Study and Extension Phase	The number of participants that have remained seizure free for at least a 24 month consecutive period from the start of the Flexible Dosing Period (FDP: the period following the Titration Period and leading into the Maintenance Period) in the base study through the treatment period of this study. Seizure freedom was defined as the absence of all seizure regardless of seizure type.	Week 5 to Week 109 (in base study) and Month 1 to Month 27 (in extension phase)	No
Secondary	Change From Baseline in Quality of Life Assessed by Quality of Life in Epilepsy-Problems Questionnaire (QOLIE-31-P) Overall Score at Each Visit	The QOLIE-31-P is a 31-item questionnaire evaluating a participant's QOL perception in 7 domains: seizure worry,emotional well being,energy/fatigue, cognitive functioning, medication effects, social functioning,overall QOL. The overall score is derived by weighing and then summing the 7 domain scores. Precoded numeric values for some domains are such that a higher number reflects a more favorable health state; others are such that a higher number reflects a less favorable state. Precoded values are converted to 0-100 point scores; higher converted scores always reflect better QOL.	Weeks 0, 26, 52, 78 and 117	No