Clinical Study of Lamotrigine to Treat Newly Diagnosed Typical Absence Seizure in Children and Adolescents
Information source: GlaxoSmithKline
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Epilepsy
Intervention: Lamictal (Drug)
Phase: Phase 3
Status: Active, not recruiting
Sponsored by: GlaxoSmithKline Official(s) and/or principal investigator(s): GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline
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.
Clinical Details
Official title: A Multi-center, Uncontrolled, Open-label, Evaluation of Lamotrigine Monotherapy on Newly Diagnosed Typical Absence Seizures in Children and Adolescents
Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Number of Participants Who Were Seizure Free as Confirmed by Hyperventilation (HV)-Electroencephalography (EEG) at the End of the Maintenance Phase (MP)
Secondary outcome: Number of Participants Who Were Seizure Free as Confirmed by HV-EEG at Two Consecutive Visits in the Escalation Phase (EP)Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs at Each Dose During the Escalation Phase Number of Participants Who Were Seizure Free as Confirmed by HV-clinical Signs During Week 4 and Week 8 of the Maintenance Phase Number of Days With Seizure Episodes Per Week in the Main Study (Fixed Escalation Phase [FEP], Escalation Phase [EP], and Maintenance Phase [MP])
Eligibility
Minimum age: 2 Years.
Maximum age: 15 Years.
Gender(s): Both.
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.
Locations and Contacts
GSK Investigational Site, Aichi 453-8511, Japan
GSK Investigational Site, Ehime 790-8524, Japan
GSK Investigational Site, Ehime 791-0295, Japan
GSK Investigational Site, Fukuoka 807-8555, Japan
GSK Investigational Site, Fukuoka 814-0180, Japan
GSK Investigational Site, Hiroshima 730-8518, Japan
GSK Investigational Site, Hokkaido 006-0041, Japan
GSK Investigational Site, Hokkaido 060-8648, Japan
GSK Investigational Site, Kanagawa 232-8555, Japan
GSK Investigational Site, Niigata 950-2085, Japan
GSK Investigational Site, Okayama 700-8558, Japan
GSK Investigational Site, Shizuoka 430-8558, Japan
GSK Investigational Site, Tokyo 113-8603, Japan
GSK Investigational Site, Seoul 120-752, Korea, Republic of
Additional Information
Starting date: September 2011
Last updated: September 25, 2014
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