Levetiracetam Versus Oxcarbazepine as Monotherapy to Evaluate Efficacy and Safety in Subjects With Newly or Recently Diagnosed Partial Epilepsy (OPTIMAL)

A Multi-Center, Open-label, Randomized Study to Evaluate the Long Term Effectiveness of Levetiracetam as Monotherapy in Comparison With Oxcarbazepine in Subjects With Newly or Recently Diagnosed Partial Epilepsy

To evaluate the long term effectiveness of Levetiracetam (LEV) monotherapy on Treatment Failure Rate in subjects with newly diagnosed partial onset seizures with or without secondary generalized seizures, compared to Oxcarbazepine (OXC) monotherapy over 50 weeks from the first dose

Study Overview

• Status: Completed
• Conditions: Epilepsy
• Intervention / Treatment: Drug: Levetiracetam; Drug: Oxcarbazepine

Detailed Description

The study duration consists of the following periods:

• Baseline period of one week: Week -1
• Titration period of two weeks: Week 0 to Week 1
• Treatment period of 48 weeks: Week 2 to Week 50

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • 05
  • Busan, Korea, Republic of
    • 10
  • Busan, Korea, Republic of
    • 16
  • Daejeon, Korea, Republic of
    • 06
  • Daejeon, Korea, Republic of
    • 18
  • Gangwon-Do, Korea, Republic of
    • 23
  • Goyang-si, Korea, Republic of
    • 08
  • Goyang-si, Korea, Republic of
    • 09
  • Gwangju, Korea, Republic of
    • 07
  • Jung-Gu, Korea, Republic of
    • 22
  • Seongnam-si, Korea, Republic of
    • 14
  • Seoul, Korea, Republic of
    • 01
  • Seoul, Korea, Republic of
    • 02
  • Seoul, Korea, Republic of
    • 03
  • Seoul, Korea, Republic of
    • 04
  • Seoul, Korea, Republic of
    • 11
  • Seoul, Korea, Republic of
    • 12
  • Seoul, Korea, Republic of
    • 13
  • Seoul, Korea, Republic of
    • 15
  • Seoul, Korea, Republic of
    • 17
  • Seoul, Korea, Republic of
    • 20
  • Seoul, Korea, Republic of
    • 21
  • Ulsan, Korea, Republic of
    • 19

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 76 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects from 16 to 80 years, inclusive. Vulnerable subjects (e.g., under 20 years or subject with learning disability but judged to be capable to understand) may only be included where legally permitted and ethically accepted
• Subjects with newly or recently diagnosed epilepsy having experienced unprovoked partial seizures (IA, IB, IC with clear focal origin), that are classifiable according to the International Classification of Epileptic seizure (1981). Undiscriminated subjects between IC and IIE could be included
• Subjects with at least 2 unprovoked seizures separated by a minimum of 48 hours in the year preceding randomization out of which at least 1 unprovoked seizure in the 6 months preceding randomization
• Subjects with documented evidence of EEG and brain MRI or CT scan in medical records which were performed within 1 year prior to Visit 1 (V1)
• Subjects have no treatment with anti-epileptic drugs in the 6 months preceding this study. The treatment for acute seizure control is acceptable with a maximum of 2 weeks duration and if the treatment was stopped at least 1 week before V1. For Phenobarbital and Phenobarbital derivatives, a minimum of 4 weeks wash-out is requested before V1

Exclusion Criteria:

• Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other non-epileptic ictal events which could be confused with seizures
• Subject taking 1 or more of the following medications on a regular basis within 28 days prior to Visit 1: neuroleptics, monoamine oxidase (MAO) inhibitors and narcotic analgesics
• Subject taking any immunosuppressant within 28 days prior to Visit 1
• Subject has a history of suicide attempt, has received professional counseling for suicidal ideation, or is currently experiencing active suicidal ideation
• Subject has a seizure disorder characterized primarily by isolated auras (ie, simple partial seizures without observable motor signs)
• Subject suffering from seizures other than partial (IA, IB, IC, with clear focal origin) seizures
• Subject has a history of status epilepticus within last 3-month period prior to Visit 1
• Subject has seizures that are uncountable due to clustering (ie, an episode lasting less than 30 minutes in which several seizures occur with such frequency that the initiation and completion of each individual seizure cannot be distinguished) during the 12-week period prior to Visit 1 and/or during the Screening Period
• Body weight is lower than 40 kg (< 40 kg)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levetiracetam; Levetiracetam twice a day treatment group	Drug: Levetiracetam; 250 mg and 500 mg Levetiracetam tablet, 1000 mg-3000 mg/day, maximum 50 weeks including initial up titration of 500 mg/day for 2 weeks
Active Comparator: Oxcarbazepine; Oxcarbazepine twice a day treatment group	Drug: Oxcarbazepine; 150 mg and 300 mg Oxcarbazepine tablet, 900 mg-2400 mg/day, maximum 50 weeks including 2 weeks of up titration (300 mg/day 1week then 600 mg/day 1 week)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With a Treatment Failure	Treatment failure is defined as (1) Dropout due to related intolerable adverse event, lack of efficacy or need for addition of another Antiepileptic Drug (AED), or (2) need of a 1-step down-Titration, within 50 weeks from the first dose of study medication.	Week 0 (First Dose) to Week 50

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to the First Seizure Defined as the Time From the First Dose of Medication to the Occurrence of the First Seizure During the 48 Weeks Treatment Period		From Week 2 to Week 50 (During Treatment Period )
Percentage of Subjects Who Achieved Seizure Freedom for 24 Consecutive Weeks During the 48 Weeks Treatment Period at Any Time	24-week Seizure Freedom (rate) defined as the number and percentage of subjects who achieved seizure freedom for 24 consecutive weeks during the Treatment Period at any time	From Week 2 to Week 50 (During Treatment Period )
Percentage of Subjects Who Achieved Seizure Freedom During the 48 Weeks Treatment Period	48-week Seizure Freedom (rate) defined as the number and percentage of subjects who achieved seizure freedom during the Treatment Period	From Week 2 to Week 50 (During Treatment Period )

Collaborators and Investigators

• Sponsor: Korea UCB Co., Ltd.

Publications and helpful links

General Publications

• Kim JH, Lee SK, Loesch C, Namgoong K, Lee HW, Hong SB; Korean N01367 Study Group. Comparison of levetiracetam and oxcarbazepine monotherapy among Korean patients with newly diagnosed focal epilepsy: A long-term, randomized, open-label trial. Epilepsia. 2017 Apr;58(4):e70-e74. doi: 10.1111/epi.13707.

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: December 21, 2011
• First Submitted That Met QC Criteria: December 21, 2011
• First Posted (Estimate): December 23, 2011

Study Record Updates

• Last Update Posted (Estimate): August 20, 2015
• Last Update Submitted That Met QC Criteria: July 24, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: treatment failure; partial epilepsy; Levetiracetam; Oxcarbazepine
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nootropic Agents; Levetiracetam; Oxcarbazepine
• Other Study ID Numbers: N01367; 2014-002713-32 (EudraCT Number)