A Double-blind, Placebo-controlled Study of Levetiracetam in Epilepsy Patients With Generalized Tonic-clonic Seizures (Except Partial Seizures Evolving to Secondarily Generalized Seizures)

Overview

The purpose of this study is to evaluate the efficacy, safety and tolerability of levetiracetam treatment used as adjunctive therapy in Japanese and Chinese epilepsy patients aged ≥16 years and with uncontrolled Generalized Tonic-Clonic seizures despite treatment with 1 or 2 anti-epileptic drugs.

Full Title of Study: “A Double-blind, Multicenter, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Adjunctive Treatment With Oral Levetiracetam, in Epilepsy Patients Aged ≥16 Years, With Generalized Tonic-clonic (GTC) Seizures”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: April 2014

Interventions

  • Drug: Levetiracetam
    • Oral dose at flexible increase doses: 1000 mg/day or 2000 mg/day or 3000 mg/day, twice daily, 28 weeks
  • Drug: Placebo
    • Matching oral placebo tablets twice daily for 28 weeks

Arms, Groups and Cohorts

  • Placebo Comparator: Placebo
    • Matching placebo for 28 weeks
  • Experimental: Levetiracetam
    • Levetiracetam treatment with flexible dosing of 1000 mg/day or 2000 mg/day or 3000 mg/day for 28 weeks

Clinical Trial Outcome Measures

Primary Measures

  • Percentage Change From the Combined Baseline in the Generalized Tonic-clonic Seizure Frequency Per Week Over the 28-week Treatment Period (Dose Adjustment + Evaluation Periods)
    • Time Frame: From Baseline to Week 28
    • Percentage change in generalized tonic-clonic (GTC) seizure frequency per week from Combined Baseline B over the Treatment Period A is calculated using the equation: Percentage change from Baseline = ((A-B)/B)*100. Percentage change from baseline is not defined for subjects whose baseline information is missing / unknown or equal to zero, or whose seizure frequency per week is missing / unknown. A negative value in change in generalized tonic-clonic (GTC) seizure frequency indicates a reduction of generalized tonic-clonic (GTC) seizure frequency over the 28-week treatment Period. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline

Secondary Measures

  • The Percentage Change in Generalized Tonic-clonic Seizure Frequency Per Week From the Combined Baseline Over the Evaluation Period
    • Time Frame: From Baseline to Evaluation Period (Week 12 to Week 28)
    • Percentage change in generalized tonic-clonic (GTC) seizure frequency per week from combined baseline B over the Evaluation Period A is calculated using the equation: Percentage change from Baseline = ((A-B)/B)*100. Percentage change from baseline is not defined for subjects whose baseline Information is missing / unknown or equal to zero, or whose seizure frequency per week is missing / unknown. A negative value in change in generalized tonic-clonic (GTC) seizure frequency indicates a reduction of generalized tonic-clonic (GTC) seizure frequency. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline.
  • Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Treatment Period
    • Time Frame: From Baseline to Week 28
    • A subject with an at least 50 % reduction in weekly generalized tonic-clonic (GTC) seizure frequency from Combined Baseline Period to the Treatment Period is considered a GTC 50 % responder. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline
  • Generalized Tonic-clonic Seizures 50 % Responder Rate (the Proportion of Subjects With 50 % or More Reduction From the Combined Baseline in the Frequency of Generalized Tonic-clonic Seizures) During the Evaluation Period
    • Time Frame: From Baseline to Evaluation Period (Week 12 to Week 28)
    • A subject with an at least 50 % reduction in weekly generalized tonic-clonic (GTC) seizure frequency from Combined Baseline Period to the Evaluation Period is considered a GTC 50 % responder. Combined Baseline means: a 4-week Retrospective Baseline + 4-week Prospective Baseline or 8-week Prospective Baseline
  • Generalized Tonic-clonic Seizure Freedom Over the Evaluation Period
    • Time Frame: Evaluation Period (Week 12 to Week 28)
    • A subject with a non-missing weekly generalized tonic-clonic (GTC) baseline seizure frequency and a weekly GTC seizure frequency of zero throughout the Evaluation Period, is considered as a GTC seizure-free subject on the Evaluation Period.

Participating in This Clinical Trial

Inclusion Criteria

  • An epilepsy patient with generalized tonic-clonic seizures that are classifiable according to the ILAE classification of epileptic seizures (Epilepsia, 1981) – A patient on a stable dose of 1 or 2 anti-epileptic drugs for the last 4 weeks (potassium bromide and sodium bromide for the last 12 weeks) prior to and during the combined baseline period Exclusion Criteria:

  • Presence of any sign (clinical or imaging procedures) suggesting a progressive brain lesion/disease, in particular, progressive disorder with epileptic seizures – Diagnosis of Lennox-Gastaut Syndrome – Confirmed focal epilepsy based on clinical signs (seizure types), with consistent electroencephalogram and magnetic resonance imagining features – A history of convulsive or non-convulsive status epilepticus while taking concomitant anti-epileptic drugs for the last 3 months prior to Visit 1

Gender Eligibility: All

Minimum Age: 16 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • UCB Japan Co. Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • UCB Clinical Trial Call Center, Study Director, +1 877 822 9493 (UCB)

Citations Reporting on Results

Wu L, Yagi K, Hong Z, Liao W, Wang X, Zhou D, Inoue Y, Ohtsuka Y, Sasagawa M, Terada K, Du X, Muramoto Y, Sano T. Adjunctive levetiracetam in the treatment of Chinese and Japanese adults with generalized tonic-clonic seizures: A double-blind, randomized, placebo-controlled trial. Epilepsia Open. 2018 Sep 29;3(4):474-484. doi: 10.1002/epi4.12255. eCollection 2018 Dec.

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