Open-Label Study to Assess Lacosamide Safety as Add-on Therapy for Primary Generalized Tonic-Clonic Seizures in Subjects With Epilepsy

• ClinicalTrials.gov Identifier: NCT01118949
• Recruitment Status: Completed
• First Posted: May 7, 2010
• Results First Posted: September 7, 2012
• Last Update Posted: July 17, 2018
• Sponsor: UCB BIOSCIENCES, Inc.
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES, Inc. )

Tracking Information

• First Submitted Date: May 5, 2010
• First Posted Date: May 7, 2010
• Results First Submitted Date: August 8, 2012
• Results First Posted Date: September 7, 2012
• Last Update Posted Date: July 17, 2018
• Study Start Date: May 2010
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 8, 2012)

• Change in the Number of Seizure Days With Absence Seizures From the Baseline Phase to the Maintenance Phase [ Time Frame: From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13) ]
  During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded:

  • Seizure type
  • Seizure frequency

  A negative value in change of seizure days with absence seizures shows a decrease in seizure days with absence seizures.
• Change in the Number of Seizure Days With Myoclonic Seizures From the Baseline Phase to the Maintenance Phase [ Time Frame: From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13) ]
  During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded:

  • Seizure type
  • Seizure frequency

  A negative value in change of seizure days with myoclonic seizures shows a decrease in seizure days with myoclonic seizures.

Original Primary Outcome Measures (submitted: May 6, 2010)

• Change in the number of seizure days with absence seizures from the Baseline Phase (Weeks 0 to 4) to the Maintenance Phase (Weeks 8 to 13) [ Time Frame: Baseline Phase (Weeks 0 to 4), Maintenance Phase (Weeks 8 to 13) ]
• Change in the number of seizure days with myoclonic seizures from the Baseline Phase (Weeks 0 to 4) to the Maintenance Phase (Weeks 8 to 13) [ Time Frame: Baseline Phase (Weeks 0 to 4), Maintenance Phase (Weeks 8 to 13) ]
• Percentage change in primary generalized tonic-clonic (PGTC) seizure frequency per 28 days from the Baseline Phase (Weeks 0 to 4) to the Maintenance Phase (weeks 8 to 13) [ Time Frame: Baseline Phase (Weeks 0 to 4), Maintenance Phase (Weeks 8 to 13) ]

Current Secondary Outcome Measures (submitted: August 8, 2012)

• Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) [ Time Frame: From Visit 2 (Week 4) to Visit 6 (Week 8) ]
  Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with > 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The general spike-wave discharges are calculated per interpretable hours.
• Changes in Count of 3 Hertz (Hz) Spike-wave Discharges (During Waking Hours) on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) [ Time Frame: From Visit 2 (Week 4) to Visit 6 (Week 8) ]
  Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with > 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The 3 Hertz (Hz) spike-wave discharges are calculated per awake hours.
• Number of Subjects With Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period [ Time Frame: From Visit 2 (Week 4) to Visit 7 (Week 13) ]
  An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.
• Number of Subjects Withdrawn From the Study Due to Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period [ Time Frame: From Visit 2 (Week 4) to Visit 7 (Week 13) ]
  An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.

Original Secondary Outcome Measures (submitted: May 6, 2010)

• Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) [ Time Frame: Visit 2 (i.e., Week 4), Visit 6 (i.e., Week 8) ]
• Changes in count of 3 Hertz (Hz) spike-wave discharges on 24-hour ambulatory electrocardiogram (ECG) from Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase) [ Time Frame: Visit 2 (i.e., Week 4), Visit 6 (i.e., Week 8) ]
• Number of participants with treatment emergent adverse events (TEAEs) during the 10-week Treatment Period [ Time Frame: Visit 2 (i.e., Week 4) to Visit 7 (i.e., Week 13) ]
• Number of participants withdrawn from the study due to Treatment Emergent Adverse Events (TEAEs) during the 10-week Treatment Period [ Time Frame: Visit 2 (i.e., Week 4) to Visit 7 (i.e., Week 13) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Open-Label Study to Assess Lacosamide Safety as Add-on Therapy for Primary Generalized Tonic-Clonic Seizures in Subjects With Epilepsy
• Official Title: An Open-Label Pilot Study to Assess the Safety of Oral Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy
• Brief Summary: The purpose is to assess the safety of Lacosamide in subjects with uncontrolled Primary Generalized Tonic-Clonic (PGTC) seizures with Idiopathic Generalized Epilepsy.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsy

Intervention

Drug: Lacosamide

Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.

Other Name: Vimpat®

Study Arms

Experimental: Lacosamide

Intervention: Drug: Lacosamide

• Publications *: Wechsler RT, Yates SL, Messenheimer J, Leroy R, Beller C, Doty P. Lacosamide for uncontrolled primary generalized tonic-clonic seizures: An open-label pilot study with 59-week extension. Epilepsy Res. 2017 Feb;130:13-20. doi: 10.1016/j.eplepsyres.2016.12.015. Epub 2016 Dec 29.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 8, 2011): 49
• Original Estimated Enrollment (submitted: May 6, 2010): 45
• Actual Study Completion Date: August 2011
• Actual Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject has a diagnosis of uncontrolled epilepsy with primary generalized tonic-clonic (PGTC) seizures and idiopathic generalized epilepsy. Diagnosis should have been established by an electroencephalogram (EEG) with generalized spike-wave discharges within 5 years of the screening visit
• Subject has ≥1 PGTC seizure within the 12 weeks prior to the screening visit
• Subject has a stable dose regimen of 1 to 3 marketed antiepileptic drug(s) (AEDs) with or without additional concurrent stable Vagus Nerve Stimulation (VNS). The VNS must have been in place for at least 6 months prior to study entry with constant settings for at least 28 days prior to the screening visit and during the Baseline Phase. Benzodiazepines will be counted as an AED

Exclusion Criteria:

• Subject has a history of partial-onset seizures or EEG findings consistent with partial onset seizures
• Subject has a history of status epilepticus within the 5-year Period prior to Visit 1
• Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other non-epileptic ictal events
• Subject has any medical or psychiatric condition
• Subject has any history of alcohol or drug abuse
• Subject is currently taking felbamate
• Subject has ever taken vigabatrin and has no visual fields examination report available or if results of the examination are abnormal
• Subject is on a ketogenic diet
• Subject has a known sodium channelopathy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01118949
• Other Study ID Numbers: SP0961; 2014-004379-22 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
• Study Sponsor: UCB BIOSCIENCES, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: UCB Clinical Trial Call Center; +1 877 822 9493 (UCB)

• PRS Account: UCB Pharma
• Verification Date: March 2018