Trial Outcomes & Findings for Clinical Study of Lamotrigine to Treat Newly Diagnosed Epilepsy (NCT NCT01431963)
NCT ID: NCT01431963
Last Updated: 2016-10-20
Results Overview
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.
COMPLETED
PHASE3
70 participants
Weeks 7 to 30
2016-10-20
Participant Flow
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.
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.
Participant milestones
| Measure |
Lamotrigine
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.
|
|---|---|
|
Overall Study
STARTED
|
67
|
|
Overall Study
Begin Escalation Phase (EP; 6 Weeks)
|
67
|
|
Overall Study
Received Treatment
|
65
|
|
Overall Study
Complete EP (6 Weeks)
|
52
|
|
Overall Study
Begin Maintenance Phase (MP; 24 Weeks)
|
52
|
|
Overall Study
Complete MP (24 Weeks)
|
42
|
|
Overall Study
Begin Extension Phase (ExP; gt= 24weeks)
|
19
|
|
Overall Study
Complete ExP (gt= 24 Weeks)
|
19
|
|
Overall Study
COMPLETED
|
32
|
|
Overall Study
NOT COMPLETED
|
35
|
Reasons for withdrawal
| Measure |
Lamotrigine
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.
|
|---|---|
|
Overall Study
Adverse Event
|
18
|
|
Overall Study
Lack of Efficacy
|
7
|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Protocol-defined Stopping Criteria
|
2
|
|
Overall Study
Physician Decision
|
4
|
|
Overall Study
Withdrawal by Subject
|
3
|
Baseline Characteristics
Clinical Study of Lamotrigine to Treat Newly Diagnosed Epilepsy
Baseline characteristics by cohort
| Measure |
Lamotrigine
n=65 Participants
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.
|
|---|---|
|
Age, Continuous
|
37.3 Years
STANDARD_DEVIATION 20.20 • n=5 Participants
|
|
Sex: Female, Male
Female
|
26 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
39 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian Heritage
|
26 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - Japanese Heritage
|
39 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Weeks 7 to 30Population: Full Analysis Set (FAS): all participants in the Safety Population (SP) who provided at least one set of efficacy data after the first dosing of investigational product. The SP is comprised of all participants who had taken at least one dose of investigational product. Only those participants available at the specified time point were analyzed.
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.
Outcome measures
| Measure |
Lamotrigine
n=65 Participants
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.
|
|---|---|
|
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)
All, n=65
|
28 participants
|
|
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)
A+B+C, n=55
|
22 participants
|
|
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)
A+B, n=42
|
17 participants
|
|
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)
C, n=33
|
23 participants
|
|
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)
D5, n=10
|
8 participants
|
SECONDARY outcome
Timeframe: up to Week 30Population: FAS. Only those participants available at the specified time point were analyzed.
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.
Outcome measures
| Measure |
Lamotrigine
n=65 Participants
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.
|
|---|---|
|
Time to Withdrawal/Dropout From the Study (Across Seizure Types and by Seizure Type in Past 6 Months in the Escalation and Maintenance Phases)
All, n=65
|
150.0 Days
Standard Error 8.99
|
|
Time to Withdrawal/Dropout From the Study (Across Seizure Types and by Seizure Type in Past 6 Months in the Escalation and Maintenance Phases)
A+B+C, n=55
|
148.4 Days
Standard Error 9.72
|
|
Time to Withdrawal/Dropout From the Study (Across Seizure Types and by Seizure Type in Past 6 Months in the Escalation and Maintenance Phases)
A+B, n=42
|
147.9 Days
Standard Error 10.72
|
|
Time to Withdrawal/Dropout From the Study (Across Seizure Types and by Seizure Type in Past 6 Months in the Escalation and Maintenance Phases)
C, n=33
|
168.0 Days
Standard Error 10.91
|
|
Time to Withdrawal/Dropout From the Study (Across Seizure Types and by Seizure Type in Past 6 Months in the Escalation and Maintenance Phases)
D5, n=10
|
14.6 Days
Standard Error 0.54
|
SECONDARY outcome
Timeframe: Weeks 7 to 30Population: FAS. Only those participants available at the specified time point were analyzed.
The time to the first seizure in the Maintenance Phase is measured at the time the first seizure occurred in 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.
Outcome measures
| Measure |
Lamotrigine
n=52 Participants
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.
|
|---|---|
|
Time to the First Seizure in the Maintenance Phase (Across Seizure Types and by Seizure Type)
All, n=52
|
103.0 Days
Standard Error 9.43
|
|
Time to the First Seizure in the Maintenance Phase (Across Seizure Types and by Seizure Type)
A+B+C, n=44
|
100.4 Days
Standard Error 10.44
|
|
Time to the First Seizure in the Maintenance Phase (Across Seizure Types and by Seizure Type)
A+B, n=34
|
94.2 Days
Standard Error 12.22
|
|
Time to the First Seizure in the Maintenance Phase (Across Seizure Types and by Seizure Type)
C, n=29
|
113.3 Days
Standard Error 12.06
|
|
Time to the First Seizure in the Maintenance Phase (Across Seizure Types and by Seizure Type)
D5, n=8
|
NA Days
Standard Error NA
No participants had D5 seizures in the Maintenance Phase (MP); thus, mean time to the first D5 seizure in the MP could not be calculated.
|
Adverse Events
Lamotrigine
Serious adverse events
| Measure |
Lamotrigine
n=65 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Haemorrhoids
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Cardiac disorders
Sick sinus syndrome
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Investigations
Electrocardiogram QT prolonged
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Nervous system disorders
Epilepsy
|
3.1%
2/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Injury, poisoning and procedural complications
Pulmonary contusion
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
1.5%
1/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
Other adverse events
| Measure |
Lamotrigine
n=65 participants at risk
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.
|
|---|---|
|
Nervous system disorders
Headache
|
21.5%
14/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Nervous system disorders
Dizziness
|
6.2%
4/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Infections and infestations
Nasopharyngitis
|
23.1%
15/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Skin and subcutaneous tissue disorders
Rash
|
12.3%
8/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Gastrointestinal disorders
Nausea
|
9.2%
6/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
6.2%
4/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.2%
4/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
|
Psychiatric disorders
Insomnia
|
6.2%
4/65 • Serious adverse events (SAEs) and non-serious AEs were collected from study medication start until the end of treatment (up to Week 54).
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.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER