Trial to Demonstrate the Efficacy and Safety of Conversion to Lacosamide Monotherapy for Partial-onset Seizures (ALEX-MT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma
ClinicalTrials.gov Identifier:
NCT00520741
First received: August 24, 2007
Last updated: August 27, 2014
Last verified: May 2014
  Purpose

The objective of this historical-controlled trial is to demonstrate the efficacy and safety of conversion to Lacosamide monotherapy in subjects with Partial-onset Seizures who are withdrawn from 1 to 2 marketed antiepileptic drugs.


Condition Intervention Phase
Epilepsy
Drug: Lacosamide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Historical-controlled, Multicenter, Double-blind, Randomized Trial to Assess the Efficacy and Safety of Conversion to Lacosamide 400 mg/Day Monotherapy in Subjects With Partial-onset Seizures

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Percentage of Subjects (Using Kaplan-Meier) Who Are Identified As Meeting At Least 1 Pre-defined Exit Criteria By Day 112 Relative To The Start of Withdrawal of Background Antiepileptic Drug(s) [ Time Frame: 16 Weeks Maintenance Period (approximately 112 days) ] [ Designated as safety issue: No ]

    Pre-defined exit criteria:

    1. A 2-fold or greater increase in average monthly (28-day) partial seizure frequency (motor and non-motor) compared to average monthly partial seizure frequency (motor and non-motor) during the Baseline Phase
    2. A 2-fold or greater increase in consecutive 2-day partial seizure frequency (motor and non-motor) versus the highest consecutive 2-day partial seizure frequency (motor and non-motor) that occurred during the Baseline Phase.

      Note: if the highest consecutive 2-day partial seizure frequency during the Baseline Phase is 1, a 2-day partial seizure frequency of ≥3 is required to meet this exit criterion

    3. Occurrence of a single generalized tonic-clonic seizure if none had occurred in the 6 months prior to randomization
    4. A prolongation or worsening of overall seizure duration, frequency, type or pattern considered by the investigator as serious enough to warrant trial discontinuation
    5. Status epilepticus, or new onset of serial/cluster seizures


Secondary Outcome Measures:
  • Time to First Occurrence of Any Exit Event During The Maintenance Period [ Time Frame: 16 Weeks Maintenance Period (approximately 112 days) ] [ Designated as safety issue: No ]
    The time to first occurrence (days) of any exit event was estimated using Kaplan-Meier methods and was based on the time from the start of the Maintenance Phase to the earliest date a subject met an exit criterion. Subjects who discontinued during the Maintenance Phase due to non-exit criteria reasons or who completed the Maintenance Phase before 112 days and did not meet an exit criterion were censored as of the last Maintenance Phase dose date. Subjects completing 112 days in the Maintenance Phase were censored as of Day 112.

  • Percentage of Subjects (Using Kaplan-Meier) Who Are Identified as Meeting at Least 1 Pre-defined Exit Criteria by Day 112, Withdrew Due to Adverse Event (AE) or Withdrew Due to Lack of Efficacy During The Maintenance Period [ Time Frame: 16 Weeks Maintenance Period (approximately 112 days) ] [ Designated as safety issue: No ]

    Subjects were classified as having an exit event if they experienced at least 1 of the following events during the Maintenance Phase as of Day 112:

    1. Met at least 1 exit criterion based on the calculations applied for the Primary Efficacy Analysis
    2. Withdrawal due to AE with onset during the Maintenance Phase
    3. Withdrew prematurely due to lack of efficacy during the Maintenance Phase

    The date the subject experienced the event was set to the earliest date the subject met an exit criterion or the date of the last Maintenance Phase dose for subjects not meeting an exit criterion but withdrawing due to an AE or lack of efficacy.

    The secondary analysis is only conducted on the Lacosamide 400 mg/day group.


  • Duration of Monotherapy Treatment During the Monotherapy Phase of The Maintenance Period (Visit 9 - Visit 12) [ Time Frame: Visit 9 - Visit 12 (approximately 10 weeks) ] [ Designated as safety issue: No ]
    Days on Monotherapy Treatment were defined as the number of days during the Monotherapy Phase when the subject took Lacosamide (LCM) only (ie, the total number of days exposed to LCM during the Monotherapy Phase minus any days where a concomitant or rescue Anti-epileptic Drug (AED) was taken by the subject). The days on Monotherapy Treatment did not need to be consecutive.

  • Clinical Global Impression of Change (CGIC) From Baseline To Last Visit [ Time Frame: Baseline; Last Visit (approximately 27 weeks) ] [ Designated as safety issue: No ]

    For the assessment of the Clinical Global Impression of Change (CGIC), the investigator should provide his/her assessment of the subject's clinical status, compared to Baseline, including an evaluation of seizure frequency and intensity, the occurrence of AEs, and subject's functional status. He was asked the following:Please check the number that best describes the subject's condition over the past 4 weeks compared to Baseline:

    1. Very much improved
    2. Much improved
    3. Minimally improved
    4. No change
    5. Minimally worse
    6. Much worse
    7. Very much worse

  • Patient's Global Impression of Change (PGIC) From Baseline To Last Visit [ Time Frame: Baseline; Last Visit (approximately 27 weeks) ] [ Designated as safety issue: No ]

    For the assessment of the Patient's Global Impression of Change, the subject should provide his/her assessment of his/her own clinical status, compared to Baseline, including an evaluation of seizure frequency and intensity, the occurrence of AEs, and subject's functional status.The subject was asked to answer the following:

    Over the past 4 weeks, how have you felt compared to before you entered this clinical trial? (Please check the number that best describes your condition.)

    1. Very much improved
    2. Much improved
    3. Minimally improved
    4. No change
    5. Minimally worse
    6. Much worse
    7. Very much worse


Enrollment: 426
Study Start Date: August 2007
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lacosamide 400 mg/day
Lacosamide 400 mg/day
Drug: Lacosamide
50 mg and 100 mg tablets provided for 200 mg twice daily dosing for up to 20 weeks.
Other Name: Vimpat
Active Comparator: Lacosamide 300 mg/day
Lacosamide 300 mg/day
Drug: Lacosamide
50 mg and 100 mg tablets provided for 150 mg twice daily dosing for up to 20 weeks.
Other Name: Vimpat

Detailed Description:

Sudden unexplained death in epilepsy have been reported in epilepsy patients. A causal relationship with the administration of antiepileptic drugs has not been established. The most important known risk factor for sudden unexplained death in epilepsy (SUDEP) is the occurrence and frequency of generalized tonic-clonic seizures (GTCS). Twenty-seven patients with only GTCS were enrolled in the conversion to monotherapy study. In this study, two patients with only GTCS had SUDEP. Due to the potential increased risk of SUDEP in patients with only GTCS in a trial setting, the 1 remaining patient with only GTCS was withdrawn from this study.

  Eligibility

Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject has a diagnosis of Epilepsy with Simple Partial Seizures (motor component) and or Complex Partial Seizures (with or without secondary generalization)
  • Must be experiencing 2 to 40 seizures per 28-day period
  • Stable dose of 1 or 2 marketed antiepileptic drugs
  • Second Antiepileptic Drug (AED) must be less than or equal to 50 % of the minimum recommended maintenance dose per USA product label at screening

Exclusion Criteria:

  • Subject has a history of primary generalized or unclassified seizures
  • Seizure disorder primarily characterized by isolated auras
  • History of status epilepticus
  • Seizures that are uncountable due to clustering
  • Has greater than 5 seizures/day
  • Subjects taking Benzodiazepines, Phenobarbital or Primidone
  • Subject has Vagus Nerve Stimulation (VNS)
  • Significant medical or psychiatric condition
  • History of alcohol or drug abuse
  • History of Ethosuximide use, Felbamate use after 1994 or Vigabatrin use after 1997
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00520741

  Show 158 Study Locations
Sponsors and Collaborators
UCB Pharma
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Additional Information:
No publications provided by UCB Pharma

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: UCB Pharma
ClinicalTrials.gov Identifier: NCT00520741     History of Changes
Obsolete Identifiers: NCT01058954
Other Study ID Numbers: SP902, 2007-005439-27
Study First Received: August 24, 2007
Results First Received: November 26, 2013
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Spain: Spanish Agency of Medicines
Denmark: Danish Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Canada: Health Canada
Australia: Department of Health and Ageing Therapeutic Goods Administration
Italy: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by UCB Pharma:
Epilepsy
Partial Onset Seizures
Lacosamide
Monotherapy
Vimpat

Additional relevant MeSH terms:
Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Lacosamide
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014