Clinical Trial Results:
A multi-center, uncontrolled, open-label, evaluation of Lamotrigine monotherapy on newly diagnosed typical absence seizures in children and adolescents
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Summary
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EudraCT number |
2017-001514-29 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
20 Nov 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Oct 2017
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First version publication date |
20 Oct 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
115377
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Mar 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 Nov 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy and safety of lamotrigine monotherapy orally administered once daily in children and adolescent patients with newly diagnosed typical absence seizures in Japan and South Korea.
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
29 Sep 2011
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Japan: 16
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Country: Number of subjects enrolled |
Korea, Republic of: 4
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Worldwide total number of subjects |
20
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
19
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Adolescents (12-17 years) |
1
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Participants with newly diagnosed and untreated typical absence seizure; aged 2-15 years in Japan, 2-12 years in South Korea at the time of obtaining consent; weighing at least 7 kilograms (kg); without partial seizure or generalized seizures other than typical absence; and without a history of rash associated with other treatment were enrolled. | ||||||||||||||||||
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Pre-assignment
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Screening details |
The study consisted of an Escalation Phase (EP), a 12-week (W) Maintenance Phase (MP), a >=2-week Taper Phase, and post-study examination within 1-4 weeks after the last dose of lamotrigine. Participants could have entered the Extension Phase (ExP) until approval for this indication or until 24 months after the Last Subject Last Visit in the MP. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Lamotrigine | ||||||||||||||||||
Arm description |
In the EP, lamotrigine 0.3 milligrams per kilogram per day (mg/kg/day) was administered orally once daily from Week W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, whichever was less (WWL), until a seizure-free (SF) status was confirmed by hyperventilation (HV)-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at >=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose <1.2 mg/kg/day or >10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Lamotrigine 2 mg tablet
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
White chewable dispersible tablet containing Lamotrigine 2 mg was administered once daily in the evening.
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Investigational medicinal product name |
Lamotrigine 5 mg tablet
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
White chewable dispersible tablet containing Lamotrigine 5 mg was administered once daily in the evening.
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Investigational medicinal product name |
Lamotrigine 25 mg tablet
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
White chewable dispersible tablet containing Lamotrigine 25 mg was administered once daily in the evening.
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Investigational medicinal product name |
Lamotrigine 100 mg tablet
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
White chewable dispersible tablet containing Lamotrigine 100 mg was administered once daily in the evening.
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Baseline characteristics reporting groups
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Reporting group title |
Lamotrigine
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Reporting group description |
In the EP, lamotrigine 0.3 milligrams per kilogram per day (mg/kg/day) was administered orally once daily from Week W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, whichever was less (WWL), until a seizure-free (SF) status was confirmed by hyperventilation (HV)-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at >=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose <1.2 mg/kg/day or >10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Lamotrigine
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Reporting group description |
In the EP, lamotrigine 0.3 milligrams per kilogram per day (mg/kg/day) was administered orally once daily from Week W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, whichever was less (WWL), until a seizure-free (SF) status was confirmed by hyperventilation (HV)-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at >=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose <1.2 mg/kg/day or >10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study. | ||
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End point title |
Number of participants who were seizure free as confirmed by hyperventilation (HV)-electroencephalography (EEG) at the end of the Maintenance Phase (MP) [1] | ||||||
End point description |
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. The estimated value reflects the percentage of participants who were seizure free.
Full Analysis Set (FAS): all participants who took at least one dose of investigational product and contributed data to at
least one efficacy measure after the first dosing of investigational product
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End point type |
Primary
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End point timeframe |
Week 12 of the Maintenance Phase (up to Study Week 50)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical Analyses for one arm studies can not be entered into the system. |
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| Notes [2] - FAS |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of participants who were seizure free as confirmed by HV-EEG at two consecutive visits in the Escalation Phase (EP) | ||||||
End point description |
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.
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End point type |
Secondary
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End point timeframe |
Up to Study Week 49
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| Notes [3] - FAS |
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| No statistical analyses for this end point | |||||||
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End point title |
Number of participants who were seizure free as confirmed by HV-clinical signs at each dose during the Escalation Phase | ||||||||||||||||||||||||||||||||||||||
End point description |
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).
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End point type |
Secondary
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End point timeframe |
Up to Study Week 49
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| Notes [4] - FAS. Only those participants given the indicated dose of investigational product were analyzed. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
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End point title |
Number of participants who were seizure free as confirmed by HV-clinical signs during Week 4 and Week 8 of the Maintenance Phase | ||||||||||
End point description |
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).
FAS. Only those participants who were dosed with investigational product at the indicated time points were analyzed.
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End point type |
Secondary
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End point timeframe |
Week 4 and Week 8 of the Maintenance Phase (up to Study Weeks 42 and 46, respectively)
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| Notes [5] - FAS |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of participants who were seizure free as confirmed by HV-EEG at each assessment point in the Extension Phase (ExP) | ||||||||||||||||||||
End point description |
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).
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End point type |
Secondary
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End point timeframe |
Extension Week 12 (Extension Visit 1 [Ext-V1]), every 24 weeks after Ext-V1 and until withdrawal
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| Notes [6] - FAS. Only those participants given the indicated dose of investigational product were analyzed. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number of participants who were seizure free as confirmed by HV-clinical signs at each assessment point in the Extension Phase (ExP) | ||||||||||||||||||||
End point description |
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).
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End point type |
Secondary
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End point timeframe |
Extension Week 24 (Extension Visit 2 [Ext-V2], every 24 weeks after the Ext-V2 and until withdrawal
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| Notes [7] - FAS. Only those participants given the indicated dose of investigational product were analyzed. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point 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) | ||||||||||||||||
End point description |
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)
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End point type |
Secondary
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End point timeframe |
Up to Study Week 50
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| Notes [8] - FAS |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Number of days with seizure episodes per week in the Extension Phase (ExP) Overall | ||||||||
End point description |
Participants were asked to record the seizure codes, seizure duration, and their physical condition in a diary provided.
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End point type |
Secondary
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End point timeframe |
Extension Week 12 (Extension Visit 1 [Ext-V1], every 12 week after Ext-V1 and until withdrawal
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| Notes [9] - FAS. Only those participants given the indicated dose of investigational product were analyzed. |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Study Week 50) (EP, MP, and ExP).
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Adverse event reporting additional description |
SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who had taken at least one dose of investigational product.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
Lamotrigine
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Reporting group description |
In the EP, lamotrigine 0.3 mg/kg/day was administered orally once daily from W1 to W2, and 0.6 mg/kg/day from W3 to W4. From W5, the dose was escalated by 0.6 mg/kg/day once every 1 or 2 weeks, up to a maximum of 10.2 mg/kg/day or 400 mg/day, WWL, until a SF status was confirmed by HV-clinical signs. After a SF confirmation, the dose was increased by one level and HV-electroencephalography was assessed twice at the same dose level to confirm the SF status. In the MP, the same dose was continued for 12 weeks. An increase/decrease in dose (0.6 mg/kg/day at >=1-week intervals) was allowed within the range of 1.2 to 10.2 mg/kg/day or 400 mg/day, WWL. In the ExP, doses of 1.2 to 10.2 mg/kg/day or 400 mg/day (WWL) were administered based on seizure status/safety. If a dose <1.2 mg/kg/day or >10.2 mg/kg/day or 400 mg/day (WWL) was necessary, the participant was withdrawn from the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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01 Nov 2011 |
To change Sponsor’s representative; To change PGx contact information; To correct typos and error |
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09 Apr 2012 |
To change Study Director; To change the corporate name and the responsible person of emergency contact information (Japan only); To change the necessity of Hyperventilation electroencephalography (HV-EEG) test on withdrawal visit during the escalation Phase. |
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18 Feb 2013 |
To change Study Director; By reorganization of sponsor; By modification to sponsor information (Japan only); To correct typos and errors (Japan) |
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03 Jul 2014 |
To change Study Administrative Structure (Japan only) |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
