Clinical Trial: Clinical Study of Lamotrigine to Treat Newly Diagnosed Typical Absence Seizure in Children and Adolescents

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-center, Uncontrolled, Open-label, Evaluation of Lamotrigine Monotherapy on Newly Diagnosed Typical Absence Seizures in Children and Adolescents

Brief Summary:

This is a multi-center, uncontrolled, open-label study to evaluate the efficacy and safety of lamotrigine monotherapy on newly diagnosed typical absence seizure in children and adolescents in Japan and South Korea.

The study period is composed the baseline, fixed escalation phase, escalation phase, maintenance phase, taper phase, and post study examination. During the fixed escalation phase, the investigational product is administered at 0.3 mg/kg/day for 2 weeks (Week 1 to 2), followed by 0.6 mg/kg/day for 2 weeks (Week 3 to 4). Subjects thereafter visit the clinic once every 1 to 2 weeks during the escalation phase to increase the dose by 0.6 mg/kg/day up to a maximum of 10.2 mg/kg/day or 400 mg/day (whichever was less) until patients are confirmed to be seizure-free by HV tests for clinical signs. After seizure free is confirmed by HV-clinical signs, the dose is increased by one level and HV-EEG (electroencephalography) test (first test) is assessed at the next visit. If seizure free is observed by HV-EEG, the same dose is administered. Thereafter, HV-EEG (second test) is assessed at the next visit and if seizure free is confirmed again, the subjects enter the 12-week maintenance phase. During the maintenance phase, patients visit the clinic once every 4 weeks. The dose can be adjusted as necessary within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day (whichever was less) taking into account the status of seizures and the safety. The investigational product is administered once daily (in the evening). However, if the number of tablets is large, twice-daily administration (in the morning and evening) is also allowed. After the completion of maintenance phase, subjects who have responded to lamotrigine without tolerability issues are eligible to enter the extension phase of the study if clinically indicated.

Detailed Summary:
Sponsor: GlaxoSmithKline

Current Primary Outcome: Number of Participants Who Were Seizure Free as Confirmed by Hyperventilation (HV)-Electroencephalography (EEG) at the End of the Maintenance Phase (MP) [ Time Frame: Week 12 of the Maintenance Phase (up to Study Week 50) ]

Original Primary Outcome: • Proportion of subjects seizure-free confirmed by HV-EEG at the end of the maintenance phase [ Time Frame: This outcome is measured at the end of the maintenance phase (at the average of Week 32). ]

Current Secondary Outcome:

• Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Two Consecutive Visits in the Escalation Phase (EP) [ Time Frame: Up to Study Week 49 ]
  EEG is a diagnostic test for epilepsy. The EEG machine records the brain's electrical activity as a series of waveforms. HV is an activation technique used to provoke seizures during an EEG recording. An approximately 30-minute EEG with HV was performed on participants in a supine position. In the HV test, participants breathed through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute ) for 4 continuous minutes using a pin-wheel provided to them.
• Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase [ Time Frame: Up to Study Week 49 ]
  HV is an activation technique used to provoke seizures. Participants were instructed to breathe through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute) for 4 continuous minutes while sitting using a pin-wheel and were observed for clinical signs of seizures like impairment of consciousness; staring; eye enrollment; eye blinking; chewing movements; hand movement; other automatisms; atonic, tonic, clonic components; autonomic components; or any other signs. During the Escalation Phase, HV-clinical signs were assessed to confirm a status of seizure free. Only participants data available at the analysis time point were analyzed (represented as n=X, X, X in category title).
• Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs During Week 4 and Week 8 of the Maintenance Phase [ Time Frame: Week 4 and Week 8 of the Maintenance Phase (up to Study Weeks 42 and 46, respectively) ]
  HV is an activation technique used to provoke seizures. Participants were instructed to breathe through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute) for 4 continuous minutes while sitting using a pin-wheel and were observed for clinical signs of seizures like impairment of consciousness; staring; eye enrollment; eye blinking; chewing movements; hand movement; other automatisms; atonic, tonic, clonic components; autonomic components; or any other signs. During the Maintenace Phase, HV-clinical signs were assessed at Visit 1 (Week 4) and Visit 2 (Week 4).
• Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Each Assessment Point in the Extension Phase (ExP) [ Time Frame: Extension Week 12 (Extension Visit 1 [Ext-V1]), every 24 weeks after Ext-V1 and until withdrawal ]
  EEG is a diagnostic test for epilepsy. The EEG machine records the brain's electrical activity as a series of waveforms. HV is an activation technique used to provoke seizures during an EEG recording. An approximately 30-minute EEG with HV was performed on participants in a supine position. In the HV test, participants breathed through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute ) for 4 continuous minutes using a pin-wheel provided to them. Only participants data available at the analysis time point were analyzed (represented as n=X, X, X in category title).
• Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Assessment Point in the Extension Phase (ExP) [ Time Frame: Extension Week 24 (Extension Visit 2 [Ext-V2], every 24 weeks after the Ext-V2 and until withdrawal ]
  HV is an activation technique used to provoke seizures. Participants were instructed to breathe through their mouths deeply and rapidly (at a rate of approximately 20-25 breaths/minute) for 4 continuous minutes while sitting using a pin-wheel and were observed for clinical signs of seizures like impairment of consciousness; staring; eye enrollment; eye blinking; chewing movements; hand movement; other automatisms; atonic, tonic, clonic components; autonomic components; or any other signs. During the ExP, HV-clinical signs were assessed to confirm a status of seizure free. Only participants data available at the analysis time point were analyzed (represented as n=X, X, X in category title).
• Number of Days With Seizure Episodes Per Week in the Main Study Phase (Fixed Escalation Phase [FEP], Escalation Phase [EP], Maintenance Phase [MP]), and FEP+EP+MP) [ Time Frame: Up to Study Week 50 ]
  Participants were asked to record the seizure codes, seizure duration, and their physical condition in a diary provided. Only participants data available at the analysis time point were analyzed (represented as n=X, X, X in category title)
• Number of Days With Seizure Episodes Per Week in the Extension Phase (ExP) Overall [ Time Frame: Extension Week 12 (Extension Visit 1 [Ext-V1], every 12 week after Ext-V1 and until withdrawal ]
  Participants were asked to record the seizure codes, seizure duration, and their physical condition in a diary provided.

Original Secondary Outcome:

• • Proportion of subjects seizure-free confirmed by HV-EEG at the two consecutive visits in the escalation phase [ Time Frame: This outcome is measured in the escalation phase (from Week 5 up to approximately Week 38). ]
• • Proportion of subjects seizure-free confirmed by HV-clinical signs at each visit during the escalation phase [ Time Frame: This outcome is measured in the escalation phase (from Week 5 up to approximately Week 38). ]
• • Proportion of subjects seizure-free confirmed by HV-clinical signs during the maintenance phase [ Time Frame: This outcome is measured in the maintenance phase (approximately from Week 38 to Week 50). ]
• • Number of days with seizure episodes on seizure diary per week [ Time Frame: This outcome is measured in the escalation and the maintenance phase after start dosing up to approximately Week 50. ]

Dates:
Date Received: September 1, 2011
Date Started: September 2011
Date Completion:
Last Updated: January 25, 2017
Last Verified: January 2017