Trial Outcomes & Findings for Clinical Evaluation of BW430C in Epilepsy (NCT NCT00395694)
NCT ID: NCT00395694
Last Updated: 2018-09-26
Results Overview
Any rash event (including SJS or any other serious drug eruption) includes: all event terms containing "rash"; drug eruption; SJS; toxic epidermal necrolysis; rash generalized; and events grouped into the "Skin and Subcutaneous Tissue Disorders" system organ class per the Medical Dictionary for Regulatory Activities (MedDRA), including the above-mentioned events that the GSK medical advisors judged to be included as any rash event. SJS, also called as erythema multiforme, is a skin disorder resulting from an allergic reaction or infection.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
102 participants
Primary outcome timeframe
8 weeks
Results posted on
2018-09-26
Participant Flow
Participant milestones
| Measure |
Adults: LTG
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|
|
Escalation Phase + Maintenance Phase
STARTED
|
51
|
51
|
|
Escalation Phase + Maintenance Phase
COMPLETED
|
50
|
49
|
|
Escalation Phase + Maintenance Phase
NOT COMPLETED
|
1
|
2
|
|
Continuation Phase
STARTED
|
49
|
48
|
|
Continuation Phase
COMPLETED
|
34
|
35
|
|
Continuation Phase
NOT COMPLETED
|
15
|
13
|
Reasons for withdrawal
| Measure |
Adults: LTG
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|
|
Escalation Phase + Maintenance Phase
Adverse Event
|
1
|
2
|
|
Continuation Phase
Adverse Event
|
1
|
0
|
|
Continuation Phase
Lack of Efficacy
|
12
|
11
|
|
Continuation Phase
Withdrawal Due to Wishes of Family
|
1
|
0
|
|
Continuation Phase
Poor Compliance
|
1
|
0
|
|
Continuation Phase
Withdrawal by Subject
|
0
|
2
|
Baseline Characteristics
Clinical Evaluation of BW430C in Epilepsy
Baseline characteristics by cohort
| Measure |
Adults: LTG
n=51 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=51 Participants
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total
n=102 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
29.0 Years
STANDARD_DEVIATION 9.9 • n=5 Participants
|
8.2 Years
STANDARD_DEVIATION 4.1 • n=7 Participants
|
18.6 Years
STANDARD_DEVIATION 12.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
48 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian-Japanese
|
51 participants
n=5 Participants
|
51 participants
n=7 Participants
|
102 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Safety Population: all participants enrolled in the study who received at least one dose of study medication
Any rash event (including SJS or any other serious drug eruption) includes: all event terms containing "rash"; drug eruption; SJS; toxic epidermal necrolysis; rash generalized; and events grouped into the "Skin and Subcutaneous Tissue Disorders" system organ class per the Medical Dictionary for Regulatory Activities (MedDRA), including the above-mentioned events that the GSK medical advisors judged to be included as any rash event. SJS, also called as erythema multiforme, is a skin disorder resulting from an allergic reaction or infection.
Outcome measures
| Measure |
Adults: LTG
n=51 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=51 Participants
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=102 Participants
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Participants With Any Rash Event (Including Stevens-Johnson Syndrome [SJS] and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment
|
2 participants
|
3 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Safety Population. Only those participants who had experienced any rash event were evaluated.
Any rash event (including SJS or any other serious drug eruption) includes: all event terms containing "rash"; drug eruption; SJS; toxic epidermal necrolysis; rash generalized; and events grouped into the "Skin and Subcutaneous Tissue Disorders" system organ class per the Medical Dictionary for Regulatory Activities (MedDRA), including the above-mentioned events that the GSK medical advisors judged to be included as any rash event. SJS, also called as erythema multiforme, is a skin disorder resulting from an allergic reaction or infection.
Outcome measures
| Measure |
Adults: LTG
n=2 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=3 Participants
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=5 Participants
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Rash Events Experienced (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment
|
3 rash events
|
4 rash events
|
7 rash events
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Safety Population. Only those participants who had experienced any rash event were evaluated.
The rash events (including SJS and any other serious drug eruption) were classified into severe (rash prevents participant from leading a normal life), moderate (participant's discomfort due to rash interferes with daily life), and mild (no interference with participant's daily life due to rash), based on the intesity of the event.
Outcome measures
| Measure |
Adults: LTG
n=5 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Participants With the Indicated Intensity of Rash (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment
Severe
|
0 participants
|
—
|
—
|
|
Number of Participants With the Indicated Intensity of Rash (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment
Moderate
|
2 participants
|
—
|
—
|
|
Number of Participants With the Indicated Intensity of Rash (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment
Mild
|
3 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Safety Population. Only those participants who had experienced any rash event were evaluated.
The adverse event of rash was considered to be drug-related when the Investigator answered "Yes" to the following question: "Is there a reasonable possibility that the adverse event may have been caused by the investigational product?".
Outcome measures
| Measure |
Adults: LTG
n=5 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Drug-related and Not Related Rash Events (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment
Drug related
|
3 rash events
|
—
|
—
|
|
Number of Drug-related and Not Related Rash Events (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment
Not related to drug
|
4 rash events
|
—
|
—
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Full Analysis Set (FAS) Population: all enrolled participants except those who had no assessments of the main efficacy variable (percent reduction in seizure frequency).
Partial seizures are seizures that affect only a part of the brain at onset. Tonic-clonic seizures (grand mal seizures) affect the entire brain and are characterized by a generalized involuntary muscular contraction and cessation of respiration followed by tonic and clonic spasms of the muscles. Lennox-Gastaut syndrome (LGS) is a pediatric epilepsy syndrome characterized by multiple seizure types; mental retardation or regression; and abnormal findings on an electroencephalogram (EEG), with paroxysms of fast activity and generalized slow spike-and-wave discharges.
Outcome measures
| Measure |
Adults: LTG
n=28 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=25 Participants
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=53 Participants
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Percentage of Participants With at Least a 50 Percent Reduction in Seizure Frequency for the Indicated Types of Seizures
All Partial Seizures, n=28, 25, 53
|
17.9 percentage of participants
|
20.0 percentage of participants
|
18.9 percentage of participants
|
|
Percentage of Participants With at Least a 50 Percent Reduction in Seizure Frequency for the Indicated Types of Seizures
Tonic-clonic Seizures, n=5, 4, 9
|
60.0 percentage of participants
|
0 percentage of participants
|
33.3 percentage of participants
|
|
Percentage of Participants With at Least a 50 Percent Reduction in Seizure Frequency for the Indicated Types of Seizures
Generalized Seizures with LGS, n=25, 25, 50
|
16.0 percentage of participants
|
20.0 percentage of participants
|
18.0 percentage of participants
|
SECONDARY outcome
Timeframe: Pre-treatment (Day 0) and Week 8 of the Maintenance Phase (Study Week 14)Population: FAS Population
Percent change in seizure frequency was calculated as 100 \* (pre-treatment seizures minus MP seizures)/pre-treatment seizures. Partial seizures are seizures that affect only a part of the brain at onset. Tonic-clonic seizures (grand mal seizures) affect the entire brain and are characterized by a generalized involuntary muscular contraction and cessation of respiration followed by tonic and clonic spasms of the muscles. Lennox-Gastaut syndrome (LGS) is a pediatric epilepsy syndrome characterized by multiple seizure types, mental retardation or regression, and abnormal findings on an ECG.
Outcome measures
| Measure |
Adults: LTG
n=28 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=25 Participants
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=53 Participants
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Percent Change in Seizure Frequency of the Indicated Types of Seizures
All Partial Seizures, n=28, 25, 53
|
6.3 percent change
Interval -44.8 to 28.7
|
-11.1 percent change
Interval -46.6 to 34.6
|
-9.8 percent change
Interval -42.3 to 28.6
|
|
Percent Change in Seizure Frequency of the Indicated Types of Seizures
Tonic-clonic Seizures, n=5, 4, 9
|
83.3 percent change
The 95% confidence interval cannot be calculated because fewer than 10 events occurred.
|
27.4 percent change
The 95% confidence interval cannot be calculated because fewer than 10 events occurred.
|
36.5 percent change
Interval -47.9 to 100.0
|
|
Percent Change in Seizure Frequency of the Indicated Types of Seizures
Generalized Seizures with LGS, n=25, 25, 50
|
18.6 percent change
Interval -16.2 to 32.2
|
10.1 percent change
Interval -24.9 to 28.8
|
12.4 percent change
Interval 5.8 to 27.6
|
SECONDARY outcome
Timeframe: Up to Week 8 of the Maintenance Phase (Study Week 14)Population: Safety Population
Any rash event (including SJS or any other serious drug eruption) includes: all event terms containing "rash"; drug eruption; SJS; toxic epidermal necrolysis; rash generalized; and events grouped into the "Skin and Subcutaneous Tissue Disorders" system organ class per the Medical Dictionary for Regulatory Activities (MedDRA), including the above-mentioned events that the GSK medical advisors judged to be included as any rash event. SJS, also called as erythema multiforme, is a skin disorder resulting from an allergic reaction or infection.
Outcome measures
| Measure |
Adults: LTG
n=51 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=51 Participants
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=102 Participants
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Participants With Any Rash Event (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
|
2 participants
|
3 participants
|
5 participants
|
SECONDARY outcome
Timeframe: Up to Week 8 of the Maintenance Phase (Study Week 14)Population: Safety Population. Only those participants who had experienced any rash event were evaluated.
Any rash event (including SJS or any other serious drug eruption) includes: all event terms containing "rash"; drug eruption; SJS; toxic epidermal necrolysis; rash generalized; and events grouped into the "Skin and Subcutaneous Tissue Disorders" system organ class per the Medical Dictionary for Regulatory Activities (MedDRA), including the above-mentioned events that the GSK medical advisors judged to be included as any rash event. SJS, also called as erythema multiforme, is a skin disorder resulting from an allergic reaction or infection.
Outcome measures
| Measure |
Adults: LTG
n=2 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=3 Participants
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=5 Participants
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Rash Events Experienced (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
|
3 rash events
|
4 rash events
|
7 rash events
|
SECONDARY outcome
Timeframe: Up to Week 8 of the Maintenance Phase (Study Week 14)Population: Safety Population. Only those participants who had experienced any rash event were evaluated.
The rash events (including SJS and any other serious drug eruption) were classified into severe (rash prevents participant from leading a normal life), moderate (participant's discomfort due to rash interferes with daily life), and mild (no interference with participant's daily life due to rash), based on the intesity of the event.
Outcome measures
| Measure |
Adults: LTG
n=5 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Participants With the Indicated Intensity of Rash (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
Severe
|
0 participants
|
—
|
—
|
|
Number of Participants With the Indicated Intensity of Rash (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
Moderate
|
2 participants
|
—
|
—
|
|
Number of Participants With the Indicated Intensity of Rash (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
Mild
|
3 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to Week 8 of the Maintenance Phase (Study Week 14)Population: Safety Population. Only those participants who had experienced any rash event were evaluated.
The adverse event of rash was considered to be drug-related when the Investigator answered "Yes" to the following question: "Is there a reasonable possibility that the adverse event may have been caused by the investigational product?".
Outcome measures
| Measure |
Adults: LTG
n=5 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Drug-related and Not Related Rash Events (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
Drug related
|
3 rash events
|
—
|
—
|
|
Number of Drug-related and Not Related Rash Events (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
Not related to drug
|
4 rash events
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to Week 8 of the Maintenance Phase (Study Week 14)Population: Safety Population. Only those participants who had experienced any rash event were evaluated.
The rash adjudication committee reviewed all rash events from a dermatologic standpoint based on the nature, onset site, affected area, time to onset, outcome, and the investigator's comments to adjudicate whether or not the reported event was a drug eruption. A drug eruption is an eruption or a solitary lesion caused by a drug taken internally, often a result of allergic sensitization.
Outcome measures
| Measure |
Adults: LTG
n=3 total rash events
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=4 total rash events
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=7 total rash events
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Number of Rash Events (Including SJS and Any Other Serious Drug Eruption) Adjudicated by the Rash Adjudication Committee in Participants Taking VPA
|
1 adjudicated rash events
|
2 adjudicated rash events
|
3 adjudicated rash events
|
SECONDARY outcome
Timeframe: Week 4 and Week 8Population: Safety Population
Monocytes are a type of white blood cell (WBC; typically comprising 2%-8% of total WBCs) and are a part of the immune system. The normal range for adults is 0.2 to 0.95 \* 10\^3 cells per microliter (µL); the normal range for adolescents is 0 to 0.8 \* 10\^3 cells per µL. The monocyte count may increase during chronic inflammation, stress response, immune-mediated disease, viral fever, etc. The percentage of participants (par.) with monocyte values outside the normal range was calculated as 100 \* (number of par. with monocyte values outside the normal range) divided by the total number of par.
Outcome measures
| Measure |
Adults: LTG
n=102 Participants
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Percentage of Participants With Monocyte Values Outside the Normal Range (Shifted High) at Weeks 4 and 8
Week 4
|
15.2 percentage of participants
|
—
|
—
|
|
Percentage of Participants With Monocyte Values Outside the Normal Range (Shifted High) at Weeks 4 and 8
Week 8
|
16.2 percentage of participants
|
—
|
—
|
Adverse Events
Adults: LTG
Serious events: 5 serious events
Other events: 48 other events
Deaths: 0 deaths
Adolescents: LTG
Serious events: 2 serious events
Other events: 50 other events
Deaths: 0 deaths
Total: LTG
Serious events: 7 serious events
Other events: 98 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Adults: LTG
n=51 participants at risk
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=51 participants at risk
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=102 participants at risk
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Nervous system disorders
Sleepiness
|
2.0%
1/51
|
0.00%
0/51
|
0.98%
1/102
|
|
General disorders
Pyrexia
|
0.00%
0/51
|
2.0%
1/51
|
0.98%
1/102
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
0.00%
0/51
|
2.0%
1/51
|
0.98%
1/102
|
|
Nervous system disorders
Status epilepticus
|
2.0%
1/51
|
0.00%
0/51
|
0.98%
1/102
|
|
Infections and infestations
Pneumonia
|
2.0%
1/51
|
0.00%
0/51
|
0.98%
1/102
|
|
Gastrointestinal disorders
Vomiting
|
2.0%
1/51
|
0.00%
0/51
|
0.98%
1/102
|
|
Injury, poisoning and procedural complications
Aleviatin (phenytoin) poisoning
|
2.0%
1/51
|
0.00%
0/51
|
0.98%
1/102
|
|
Nervous system disorders
Frequent convulsions
|
0.00%
0/51
|
2.0%
1/51
|
0.98%
1/102
|
Other adverse events
| Measure |
Adults: LTG
n=51 participants at risk
Adult participants were initiated on 12.5 milligrams per day (mg/day) of BW430C (lamotrigine \[LTG\]) (as a tablet taken orally) once daily. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (maintenance phase \[MP\]). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking valproeic acid (VPA) or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative antiepileptic drugs (AEDs) were available were allowed to continue treatment with LTG until the drug is marketed (continuation phase).
|
Adolescents: LTG
n=51 participants at risk
Adolescent participants were initiated on 0.15 mg/kilogram (kg)/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
Total: LTG
n=102 participants at risk
Adult participants were initiated on 12.5 mg/day, and adolescents were initiated on 0.15 mg/kg/day. Participants had their dose increased to an optimal maintenance dose (escalation phase) and then were maintained at that dose for 8 weeks (MP). During the 8-week MP, participants received up to a maximum of 200 mg/day for adults taking VPA or up to a maximum of 400 mg/day for adults not taking VPA plus an inducer of LTG glucuronidation. During the MP, adolescents taking VPA alone received up to a maximum of 3 mg/kg/day, adolescents taking VPA with an inducer of LTG glucuronidation received up to a maximum of 5 mg/kg/day, and adolescents not taking VPA with an inducer of LTG glucuronidation received up to a maximum of 15 mg/kg/day. Participants who achieved adequate seizure control at the end of the MP and for whom no alternative AEDs were available were allowed to continue treatment with BW430C until the drug is marketed (continuation phase).
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
19.6%
10/51
|
27.5%
14/51
|
23.5%
24/102
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
9.8%
5/51
|
29.4%
15/51
|
19.6%
20/102
|
|
Nervous system disorders
Somnolence
|
13.7%
7/51
|
21.6%
11/51
|
17.6%
18/102
|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
3/51
|
21.6%
11/51
|
13.7%
14/102
|
|
General disorders
Pyrexia
|
13.7%
7/51
|
11.8%
6/51
|
12.7%
13/102
|
|
Injury, poisoning and procedural complications
Contusion
|
15.7%
8/51
|
7.8%
4/51
|
11.8%
12/102
|
|
Nervous system disorders
Dizziness
|
19.6%
10/51
|
3.9%
2/51
|
11.8%
12/102
|
|
Gastrointestinal disorders
Vomiting
|
7.8%
4/51
|
13.7%
7/51
|
10.8%
11/102
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
2.0%
1/51
|
17.6%
9/51
|
9.8%
10/102
|
|
Injury, poisoning and procedural complications
Excoriation
|
11.8%
6/51
|
3.9%
2/51
|
7.8%
8/102
|
|
Skin and subcutaneous tissue disorders
Erythema
|
2.0%
1/51
|
11.8%
6/51
|
6.9%
7/102
|
|
Gastrointestinal disorders
Constipation
|
5.9%
3/51
|
7.8%
4/51
|
6.9%
7/102
|
|
Infections and infestations
Pharyngitis
|
5.9%
3/51
|
3.9%
2/51
|
4.9%
5/102
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
3.9%
2/51
|
5.9%
3/51
|
4.9%
5/102
|
|
Psychiatric disorders
Affect lability
|
2.0%
1/51
|
7.8%
4/51
|
4.9%
5/102
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
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