A Study to Assess Tolerability and Efficacy of Topiramate Monotherapy in Recently Diagnosed Patients With Epilepsy

Open Flexible Dose Optimisation Trial Assessing Tolerability and Efficacy of Topiramate Monotherapy in Recently Diagnosed Patients With Epilepsy Who Are Treatment Naive or Have Failed One Anti-Epileptic Drug Treatment in Monotherapy

The purpose of this dose optimization study is to assess tolerability and efficacy of topiramate monotherapy in recently diagnosed patients with epilepsy who are treatment naive or have failed one anti-epileptic drug (AED) treatment in monotherapy.

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Topiramate

Detailed Description

This is an open label (all people know the identity of the intervention), dose optimization trial to assess the tolerability and efficacy of topiramate as monotherapy in recently (within 5 years) diagnosed patients with epilepsy. Treatment naive patients (patients who have never received the treatment before) and patients who failed on their first AED in monotherapy are allowed. Failure is defined as a lack of efficacy and/or tolerability of that AED and the reason for failure is recorded by the physician. A lack of efficacy is characterized when the patient has been treated with AED at target dose but the patient still has seizure. Topiramate will first be titrated up to an initial target dose that will be reached after 4-6 weeks. Further dose titration is guided by the clinical response of the individual patient, but the dose may not exceed a maximum of 400mg/day [9mg/kg/day for children]. If the patient uses an AED at entry, the AED will be fully tapered off over a period of 3 weeks, starting at the beginning of week 2, in order to have all patients on topiramate monotherapy at visit 3. Tapering the AED off may, however, extend this 3-week period if clinically indicated. Visits will be performed at baseline and after 2, 4, 8, 12, 16 weeks. The total duration for each patient in the study will be 4 months.

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Has been diagnosed with epilepsy within the past 5 years with Primary Generalized Tonic-Clonic (PGTC) seizures as well as partial onset seizures with or without secondary generalization
• Therapy naive, or being treated with their first anti-epileptic drug (AED) in monotherapy that fails in efficacy, tolerability, or both, and not in need of a combination AED therapy
• Informed Assent in children at least 7 years and older

Exclusion Criteria:

• Have pseudoseizures or the treatable cause of the seizures (eg, metabolic disorder, toxic exposure, active infection or neoplasia)
• Has any clinically relevant progressive or serious illness (eg, liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurological, psychiatric, or metabolic disturbance)
• Pregnant or breast-feeding
• Has a history or suspicion of alcohol or drug abuse
• Must have on current treatment with furosemide, hydrochlorothiazide, monoamine oxidase inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Topiramate; For children: Children will start on topiramate with a dosage of 0.5mg/kg in the evening, followed by 0.5mg/kg/day weekly increments until an initial target dose of 3mg/kg/day is reached. The total daily topiramate dose for children may, not exceed 9mg/kg/day. For adult patients: Adult patients start on topiramate with a dosage of 25mg/day in the evening, followed by weekly increments of 25 mg/day until an initial target dose of 100mg/day is reached. The dose of topiramate may be increased to the optimal dose with weekly increments of 0.5mg/kg/day and of 25 mg/day for children and adults, respectively at the discretion of the investigator.

Drug: Topiramate; The patients will receive topiramate tablet twice daily orally up to 16 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 50%, During the Last 4 Months of Treatment	Month 1, Month 3 and Month 4
Percentage of Participants Wiith Reduction in Number of Seizures Greater Than or Equal to 75%, During the Last 4 Months of Treatment	Month 1, Month 3 and Month 4
Percentage of Seizure Free Participants During the Last 4 Months of Treatment	Month 1, Month 3 and Month 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Types (Partial, Secondarily Generalized and Generalized Tonic and Clonic Siezures) After 16 Weeks		Month 1, Month 3 and Month 4
Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures as Per the Seizure Frequency (Less Than 4, 4 to 10 and Greater Than 10) After 16 Weeks		Month 4
General Clinical Assessment Before and After Treatment	The general clinical assessment is measured by clinical global impression scale. The scale is used to grade the participants as very good, good, fairly good, medium and Poor before (Visit 1) and after treatment (Visit 6).	Baseline (Day 0) and Month 4
Percentage of Participants With Greater Than or Equal to 50%, 75% and 100% Reduction in Seizures With or Without Previous Treatment		Month 4

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pte Ltd
• Investigators: Study Director: Janssen-Cilag VIETNAM Clinical Trial, Janssen-Cilag VIETNAM

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: August 23, 2012
• First Submitted That Met QC Criteria: September 17, 2012
• First Posted (Estimate): September 21, 2012

Study Record Updates

• Last Update Posted (Estimate): May 1, 2013
• Last Update Submitted That Met QC Criteria: April 26, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Epilepsy; Seizures; Topiramate; Anti-epileptic drug; Nervous disorder
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: CR017830; TOPMATEPY4049 (Other Identifier: Janssen-Cilag VIETNAM); TOP-VN -0107 (Other Identifier: Janssen-Cilag VIETNAM)