Clinical Trial Results:
A multi-center, uncontrolled, open-label, evaluation of Lamotrigine monotherapy in newly diagnosed epilepsy or recurrent epilepsy (currently untreated)
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Summary
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EudraCT number |
2015-004878-15 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
24 Oct 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Jan 2017
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First version publication date |
22 Jan 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 |
115376
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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 |
19 Feb 2015
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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 |
24 Oct 2014
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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 |
TBD
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Protection of trial subjects |
Not Applicable
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
20 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: 40
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Country: Number of subjects enrolled |
Korea, Republic of: 27
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Worldwide total number of subjects |
67
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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) |
0
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Adolescents (12-17 years) |
7
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Adults (18-64 years) |
47
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From 65 to 84 years |
12
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85 years and over |
1
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Recruitment
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Recruitment details |
A total of 70 participants were enrolled; 3 participants were screened but withdrew from the study before prescription of the first investigational product (67), and only 65 of the participants received at least one dose of the investigational product which comprised the safety population. | ||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
The study consisted of a 6-week Escalation Phase, a 24-week Maintenance Phase (MP), a >=2-week Taper Phase, and a post-study examination conducted within 1-4 weeks after the last dose of lamotrigine. In Japan only, the Extension Phase was conducted until either approval for this indication or after 24 months after 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 25 milligrams per day (mg/day) was orally administered once daily (QD; in the evening [PM]) as the initial dose from Week (W) 1 to W2. As a fixed dose escalation, lamotrigine 50 mg/day was orally administered QD (in the PM) from W3 to W4; 100 mg/day was administered from W5 to W6. In the MP, lamotrigine 200 mg/day was orally administered QD (in the PM) from W7 to W30. The dose could have been decreased to 100 mg/day per safety concerns. Per investigator discretion, the investigational product was discontinued if safety concerns remained. If the 200 mg/day dose did not control seizures, the dose could have been increased up to 400 mg/day by 50-100 mg/day at >=1-week intervals. A dose >200 mg/day could have been administered in 2 divided doses (in the morning and PM). In the ExP, lamotrigine was administered at 100-400 mg/day based on seizure status/safety. If a dose <100 or >400 mg/day was judged to be necessary, the participant was withdrawn from the study. | ||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Lamotrigine 100 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Chewable/dispersible tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Lamotrigine tablets were administered once daily or twice daily.
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Investigational medicinal product name |
Lamotrigine 25 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Chewable/dispersible tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Lamotrigine tablets were administered once daily or twice daily.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: A total of 70 participants were enrolled; 3 participants were screened but withdrew from the study before prescription of the first investigational product (67), and only 65 of the participants received at least one dose of the investigational product which comprised the safety population. [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: In Japan only, the Extension Phase was conducted until either approval for this indication or after 24 months after Last Subject Last Visit in the MP. [3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: In Japan only, the Extension Phase was conducted until either approval for this indication or after 24 months after Last Subject Last Visit in the MP |
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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 25 milligrams per day (mg/day) was orally administered once daily (QD; in the evening [PM]) as the initial dose from Week (W) 1 to W2. As a fixed dose escalation, lamotrigine 50 mg/day was orally administered QD (in the PM) from W3 to W4; 100 mg/day was administered from W5 to W6. In the MP, lamotrigine 200 mg/day was orally administered QD (in the PM) from W7 to W30. The dose could have been decreased to 100 mg/day per safety concerns. Per investigator discretion, the investigational product was discontinued if safety concerns remained. If the 200 mg/day dose did not control seizures, the dose could have been increased up to 400 mg/day by 50-100 mg/day at >=1-week intervals. A dose >200 mg/day could have been administered in 2 divided doses (in the morning and PM). In the ExP, lamotrigine was administered at 100-400 mg/day based on seizure status/safety. If a dose <100 or >400 mg/day was judged to be 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 25 milligrams per day (mg/day) was orally administered once daily (QD; in the evening [PM]) as the initial dose from Week (W) 1 to W2. As a fixed dose escalation, lamotrigine 50 mg/day was orally administered QD (in the PM) from W3 to W4; 100 mg/day was administered from W5 to W6. In the MP, lamotrigine 200 mg/day was orally administered QD (in the PM) from W7 to W30. The dose could have been decreased to 100 mg/day per safety concerns. Per investigator discretion, the investigational product was discontinued if safety concerns remained. If the 200 mg/day dose did not control seizures, the dose could have been increased up to 400 mg/day by 50-100 mg/day at >=1-week intervals. A dose >200 mg/day could have been administered in 2 divided doses (in the morning and PM). In the ExP, lamotrigine was administered at 100-400 mg/day based on seizure status/safety. If a dose <100 or >400 mg/day was judged to be necessary, the participant was withdrawn from the study. | ||
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End point title |
Number of participants who were seizure free in the Maintenance Phase (across seizure types and by seizure type within 6 months prior to the start of the study) [1] | ||||||||||||||||
End point description |
Participants were considered to be seizure free if they did not report any seizures during the Maintenance Phase. Seizure types are defined as: ALL=any type of seizure; A: simple partial seizures, B: complex partial seizures; C: partial seizures evolving to secondary generation seizures; D5: tonic-clonic seizures. Simple partial seizures are seizures that affect only a small region of the brain, often the temporal lobes or hippocampi. Complex partial seizures are epileptic seizures that are associated with bilateral cerebral hemisphere involvement and cause impairment of awareness or responsiveness. Partial seizures evolving to secondary generation seizures are seizures that start as partial seizures, then spread to include the entire brain. Tonic–clonic seizures are a type of generalized seizure that affects the entire brain.
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End point type |
Primary
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End point timeframe |
Weeks 7 to 30
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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: There are no statistical data to report. |
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| Notes [2] - Full Analysis Set population |
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Time to withdrawal/dropout from the study (across seizure types and by seizure type in past 6 months in the Escalation and Maintenance Phases) | ||||||||||||||||||
End point description |
Time to withdrawal is defined as the time from the start of treatment until withdrawal from the study. Seizure types are defined as: ALL=any type of seizure; A: simple partial seizures, B: complex partial seizures; C: partial seizures evolving to secondary generation seizures; D5: tonic-clonic seizures. Simple partial seizures are seizures which affect only a small region of the brain, often the temporal lobes or hippocampi. Simple partial seizures are seizures that affect only a small region of the brain, often the temporal lobes or hippocampi. Complex partial seizures are epileptic seizures that are associated with bilateral cerebral hemisphere involvement and cause impairment of awareness or responsiveness. Partial seizures evolving to secondary generation seizures are seizures that start as partial seizures, then spread to include the entire brain. Tonic–clonic seizures are a type of generalized seizure that affects the entire brain.
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End point type |
Secondary
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End point timeframe |
up to Week 30
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| Notes [3] - Full Analysis Set population |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Time to the first seizure in the Maintenance Phase (MP) (across seizure types and by seizure type) | ||||||||||||||||||
End point description |
The time to the first seizure in the MP is measured at the time the first seizure occurred in the MP. Seizure types are defined as: ALL=any type of seizure; A: simple partial seizures, B: complex partial seizures; C: partial seizures evolving to secondary generation seizures; D5: tonic-clonic seizures. Simple partial seizures are seizures that affect only a small region of the brain, often the temporal lobes or hippocampi. Complex partial seizures are epileptic seizures that are associated with bilateral cerebral hemisphere involvement and cause impairment of awareness or responsiveness. Partial seizures evolving to secondary generation seizures are seizures that start as partial seizures, then spread to include the entire brain. Tonic–clonic seizures are a type of generalized seizure that affects the entire brain. 99999 indicates that data were not available; no participants had D5 seizures in the MP; thus, mean time to the first D5 seizure in MP could not be calculated
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End point type |
Secondary
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End point timeframe |
Weeks 7 to 30.
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| Notes [4] - Full Analysis Set population. |
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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 Week 54).
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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 |
17.1
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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 25 mg/day was orally administered QD; in the evening(PM) as the initial dose from W1 to W2. As a fixed dose escalation, lamotrigine 50 mg/day was orally administered QD(in the PM) from W3 to W4; 100 mg/day was administered from W5 to W6. In the MP, Lamotrigine 200 mg/day was orally administered QD(PM) from W7 to W30. The dose could have been decreased to 100 mg/day per safety concerns. Per investigator discretion, the investigational product was discontinued if safety concerns remained. If the 200 mg/day dose did not control seizures, the dose could have been increased up to 400 mg/day by 50-100 mg/day at greater than or equal to 1 week intervals. A dose greater than 200 mg/day could have been administered in 2 divided doses (in the morning and PM). In the ExP, lamotrigine was administered at 100-400 mg/day based on seizure status/safety. If a dose less than 100 or greater than 400 mg/day was judged to be 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? No | |||
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 | |||
