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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01431976
First received: September 1, 2011
Last updated: August 14, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention Phase
Epilepsy
Drug: Lamictal
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-center, Uncontrolled, Open-label, Evaluation of Lamotrigine Monotherapy on Newly Diagnosed Typical Absence Seizures in Children and Adolescents

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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 Days With Seizure Episodes Per Week in the Main Study (Fixed Escalation Phase [FEP], Escalation Phase [EP], and Maintenance Phase [MP]) [ Time Frame: Up to Study Week 50 ] [ Designated as safety issue: No ]
    Participants were asked to record the seizure codes, seizure duration, and their physical condition in a diary provided.


Enrollment: 20
Study Start Date: September 2011
Estimated Study Completion Date: September 2015
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lamotrigine
No comparison
Drug: Lamictal
No comparison

  Eligibility

Ages Eligible for Study:   2 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Target disease: Subjects with newly diagnosed and untreated typical absence seizure which is classifiable by the International Classification of Seizures.
  2. Diagnosis of typical absence seizures is established by at least one of two 4-minute hyperventilation tests as supported by clinical signs and EEG findings.

    The following criteria will be used to define a typical absence seizure on the EEG: a discharge of generalized spike-and-wave or multiple spike-and-wave activity lasting ≥3 seconds during the awake state. The frequency of the spike-and-wave should be between 2.5-4.5 Hz.

  3. Age (at the time of obtaining consent):

    • 2 to 15 years of age in Japan
    • 2 to 12 years of age in South Korea
  4. Subjects must weigh at least 7 kg
  5. Outpatients
  6. Parent/guardian must have given written informed consent. Subjects who are intellectually able to understand the concepts and procedures of the protocol must give assent by also signing the consent.
  7. Gender: Male or female
  8. QTc<450 millisecond (msec) or <480msec for subjects with Bundle Branch Block - values based on either single ECG values or triplicate ECG averaged QTc values obtained over a brief recording period.

Exclusion Criteria:

  1. Subjects with partial seizure or generalized seizures other than typical absence.
  2. Subjects with a history of rash associated with other treatment.
  3. Subjects with any clinically significant chronic cardiac, renal, or hepatic medical condition. Any patient with these conditions will be excluded from the study even if these conditions are being controlled with chronic therapy.
  4. Subjects with an acute or chronic illness likely to impair drug absorption, distribution, metabolism or excretion or with any unstable physical symptoms likely to require hospitalization during participation in the study.
  5. Subjects with a psychiatric disorder requiring medication, or who had psychiatric conditions in the past that was both judged to be severe and required hospitalization.
  6. Subjects with an acute or progressive neurological disorder or an organic disease.
  7. Subjects with currently taking any psychoactive drugs to treat hyperactivity disorder or attention deficit disorder.
  8. Subjects with an unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  9. Female subjects who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study.
  10. Children in foster care: A child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. This can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or who has an appointed legal guardian.
  11. Subjects taking inducers of lamotrigine glucuronidation (i.e., rifampicin, lopinavir/ritonavir), atazanavir/ritonavir, risperidone, oral contraceptives or hormone drug which includes estrogen.
  12. Subjects having participated in other clinical study in the past 3 months before the start of investigational product.
  13. Subjects who have active suicidal plan/intent or have had active suicidal thoughts in the past 3 months before the start of investigational product or who have history of suicide attempt in the last 1 year before the start of investigational product or more than 1 lifetime suicide attempt.
  14. Subjects whom the investigator (or subinvestigator) considers ineligible for the study.
  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: NCT01431976

Locations
Japan
GSK Investigational Site
Aichi, Japan, 453-8511
GSK Investigational Site
Ehime, Japan, 791-0295
GSK Investigational Site
Ehime, Japan, 790-8524
GSK Investigational Site
Fukuoka, Japan, 807-8555
GSK Investigational Site
Fukuoka, Japan, 814-0180
GSK Investigational Site
Hiroshima, Japan, 730-8518
GSK Investigational Site
Hokkaido, Japan, 006-0041
GSK Investigational Site
Hokkaido, Japan, 060-8648
GSK Investigational Site
Kanagawa, Japan, 232-8555
GSK Investigational Site
Niigata, Japan, 950-2085
GSK Investigational Site
Okayama, Japan, 700-8558
GSK Investigational Site
Shizuoka, Japan, 430-8558
GSK Investigational Site
Tokyo, Japan, 113-8603
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 120-752
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01431976     History of Changes
Other Study ID Numbers: 115377
Study First Received: September 1, 2011
Results First Received: August 14, 2014
Last Updated: August 14, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Epilepsy, Absence
Epilepsy, Generalized
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Lamotrigine
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers

ClinicalTrials.gov processed this record on September 22, 2014