Clinical Evaluation of BW430C in Epilepsy

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00395694
• Collaborator: (none)
• Enrollment: 102
• Locations: 2
• Arm: 1
• Duration (Months): 31.6
• Patients Per Site: 51
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

To evaluate safety information of BW430C when administered using the lower starting doses and slower dose escalations as recommended Global Data Sheet

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: lamictal	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Evaluation of BW430C in Epilepsy<Phase III Study>
• Study Start Date: Aug 7, 2006
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 26, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: lamictal	Drug: lamictal; anti-epileptic drug

Outcome Measures

Primary Outcome Measures

1. 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 [8 weeks]

   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.

Secondary Outcome Measures

1. Number of Rash Events Experienced (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment [8 weeks]

   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.

2. 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 [8 weeks]

   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.

3. 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 [8 weeks]

   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?".

4. Percentage of Participants With at Least a 50 Percent Reduction in Seizure Frequency for the Indicated Types of Seizures [8 weeks]

   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.

5. Percent Change in Seizure Frequency of the Indicated Types of Seizures [Pre-treatment (Day 0) and Week 8 of the Maintenance Phase (Study Week 14)]

   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.

6. Number of Participants With Any Rash Event (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase [Up to Week 8 of the Maintenance Phase (Study Week 14)]

   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.

7. Number of Rash Events Experienced (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase [Up to Week 8 of the Maintenance Phase (Study Week 14)]

   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.

8. 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 [Up to Week 8 of the Maintenance Phase (Study Week 14)]

   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.

9. 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 [Up to Week 8 of the Maintenance Phase (Study Week 14)]

   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?".

10. Number of Rash Events (Including SJS and Any Other Serious Drug Eruption) Adjudicated by the Rash Adjudication Committee in Participants Taking VPA [Up to Week 8 of the Maintenance Phase (Study Week 14)]

    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.

11. Percentage of Participants With Monocyte Values Outside the Normal Range (Shifted High) at Weeks 4 and 8 [Week 4 and Week 8]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Epilepsy with partial seizures

• Tonic clonic seizures

• Generalized seizures of Lennox-Gastaut

• Subjects whose seizures are easily recognizable at least one seizure per month and counts for 8 consecutive weeks prior to the start of the study drug.

• Concurrent AEDs: Subjects taking concurrent VPA.

Exclusion criteria:

• Previous participation in a study of Lamictal

• Known hypersensitivity to any drugs

• Pregnant women

• nursing mothers

• women who may be pregnant

• women contemplating pregnancy during the study period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Kumamoto		Japan	860-8556
2	GSK Investigational Site

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

• Shunsuke Ohtahara, Tateki Fujiwara, Sunao Kaneko, Masafumi Iijima. Clinical Evaluation of Lamotrigine with the Current Recommended Dose in Overseas - Phase III study of lamotrigine in patients with epilepsy treated with valproate - . [J.New Rem. & Clin. Vol.57 No.9 2008]. 2008;57(J.New Rem. & Clin):1442-1453.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00395694
• Other Study ID Numbers: LAM107844
• First Posted: Nov 3, 2006
• Last Update Posted: Sep 26, 2018
• Last Verified: Aug 1, 2018

• Keywords provided by GlaxoSmithKline: epilepsy; Incidence of rash; safety evaluation for initial dose; patients with Valproic acid
• Additional relevant MeSH terms: Epilepsy; Lamotrigine

Study Results

Participant Flow

Arm/Group Title	Adults: LTG	Adolescents: LTG
Arm/Group Description	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).	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).
Period Title: Escalation Phase + Maintenance Phase
STARTED	51	51
COMPLETED	50	49
NOT COMPLETED	1	2
Period Title: Escalation Phase + Maintenance Phase
STARTED	49	48
COMPLETED	34	35
NOT COMPLETED	15	13

Baseline Characteristics

Arm/Group Title	Adults: LTG	Adolescents: LTG	Total
Arm/Group Description	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).	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 of all reporting groups
Overall Participants	51	51	102
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	29.0 (9.9)	8.2 (4.1)	18.6 (12.9)
Sex: Female, Male (Count of Participants)
Female	23 45.1%	25 49%	48 47.1%
Male	28 54.9%	26 51%	54 52.9%
Race/Ethnicity, Customized (participants) [Number]
Asian-Japanese	51 100%	51 100%	102 100%

Outcome Measures

1. Primary Outcome

Title	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
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety Population: all participants enrolled in the study who received at least one dose of study medication

Arm/Group Title	Adults: LTG	Adolescents: LTG	Total: LTG
Arm/Group Description	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).	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).	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).
Measure Participants	51	51	102
Number [participants]	2 3.9%	3 5.9%	5 4.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Total: LTG
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage of participants
	Estimated Value	4.9
	Confidence Interval	(2-Sided) 95%; 1.6 to 11.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	The estimated value represents the percentage of participants with rash events.

2. Secondary Outcome

Title	Number of Rash Events Experienced (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had experienced any rash event were evaluated.

Arm/Group Title	Adults: LTG	Adolescents: LTG	Total: LTG
Arm/Group Description	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).	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).	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).
Measure Participants	2	3	5
Number [rash events]	3	4	7

3. Secondary Outcome

Title	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
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had experienced any rash event were evaluated.

Arm/Group Title	Total: LTG
Arm/Group Description	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).
Measure Participants	5
Severe	0 0%
Moderate	2 3.9%
Mild	3 5.9%

4. Secondary Outcome

Title	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
Description	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?".
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had experienced any rash event were evaluated.

Arm/Group Title	Total: LTG
Arm/Group Description	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).
Measure Participants	5
Drug related	3
Not related to drug	4

5. Secondary Outcome

Title	Percentage of Participants With at Least a 50 Percent Reduction in Seizure Frequency for the Indicated Types of Seizures
Description	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.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Population: all enrolled participants except those who had no assessments of the main efficacy variable (percent reduction in seizure frequency).

Arm/Group Title	Adults: LTG	Adolescents: LTG	Total: LTG
Arm/Group Description	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).	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).	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).
Measure Participants	28	25	53
All Partial Seizures, n=28, 25, 53	17.9 35.1%	20.0 39.2%	18.9 18.5%
Tonic-clonic Seizures, n=5, 4, 9	60.0 117.6%	0 0%	33.3 32.6%
Generalized Seizures with LGS, n=25, 25, 50	16.0 31.4%	20.0 39.2%	18.0 17.6%

6. Secondary Outcome

Title	Percent Change in Seizure Frequency of the Indicated Types of Seizures
Description	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.
Time Frame	Pre-treatment (Day 0) and Week 8 of the Maintenance Phase (Study Week 14)

Outcome Measure Data

Analysis Population Description

FAS Population

Arm/Group Title	Adults: LTG	Adolescents: LTG	Total: LTG
Arm/Group Description	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).	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).	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).
Measure Participants	28	25	53
All Partial Seizures, n=28, 25, 53	6.3	-11.1	-9.8
Tonic-clonic Seizures, n=5, 4, 9	83.3	27.4	36.5
Generalized Seizures with LGS, n=25, 25, 50	18.6	10.1	12.4

7. Secondary Outcome

Title	Number of Participants With Any Rash Event (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
Description	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.
Time Frame	Up to Week 8 of the Maintenance Phase (Study Week 14)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Adults: LTG	Adolescents: LTG	Total: LTG
Arm/Group Description	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).	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).	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).
Measure Participants	51	51	102
Number [participants]	2 3.9%	3 5.9%	5 4.9%

8. Secondary Outcome

Title	Number of Rash Events Experienced (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase
Description	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.
Time Frame	Up to Week 8 of the Maintenance Phase (Study Week 14)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had experienced any rash event were evaluated.

Arm/Group Title	Adults: LTG	Adolescents: LTG	Total: LTG
Arm/Group Description	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).	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).	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).
Measure Participants	2	3	5
Number [rash events]	3	4	7

9. Secondary Outcome

Title	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
Description	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.
Time Frame	Up to Week 8 of the Maintenance Phase (Study Week 14)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had experienced any rash event were evaluated.

Arm/Group Title	Total: LTG
Arm/Group Description	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).
Measure Participants	5
Severe	0 0%
Moderate	2 3.9%
Mild	3 5.9%

10. Secondary Outcome

Title	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
Description	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?".
Time Frame	Up to Week 8 of the Maintenance Phase (Study Week 14)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had experienced any rash event were evaluated.

Arm/Group Title	Total: LTG
Arm/Group Description	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).
Measure Participants	5
Drug related	3
Not related to drug	4

11. Secondary Outcome

Title	Number of Rash Events (Including SJS and Any Other Serious Drug Eruption) Adjudicated by the Rash Adjudication Committee in Participants Taking VPA
Description	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.
Time Frame	Up to Week 8 of the Maintenance Phase (Study Week 14)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants who had experienced any rash event were evaluated.

Arm/Group Title	Adults: LTG	Adolescents: LTG	Total: LTG
Arm/Group Description	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).	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).	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).
Measure Participants	2	3	5
Measure total rash events	3	4	7
Number [adjudicated rash events]	1	2	3

12. Secondary Outcome

Title	Percentage of Participants With Monocyte Values Outside the Normal Range (Shifted High) at Weeks 4 and 8
Description	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.
Time Frame	Week 4 and Week 8

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Total: LTG
Arm/Group Description	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).
Measure Participants	102
Week 4	15.2 29.8%
Week 8	16.2 31.8%

Adverse Events

Arm/Group Title	Adults: LTG		Adolescents: LTG		Total: LTG
Arm/Group Description	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).		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).		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).
All Cause Mortality
	Adults: LTG		Adolescents: LTG		Total: LTG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Adults: LTG		Adolescents: LTG		Total: LTG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/51 (9.8%)		2/51 (3.9%)		7/102 (6.9%)
Gastrointestinal disorders
Vomiting	1/51 (2%)		0/51 (0%)		1/102 (1%)
General disorders
Pyrexia	0/51 (0%)		1/51 (2%)		1/102 (1%)
Infections and infestations
Pneumonia	1/51 (2%)		0/51 (0%)		1/102 (1%)
Injury, poisoning and procedural complications
Aleviatin (phenytoin) poisoning	1/51 (2%)		0/51 (0%)		1/102 (1%)
Nervous system disorders
Sleepiness	1/51 (2%)		0/51 (0%)		1/102 (1%)
Status epilepticus	1/51 (2%)		0/51 (0%)		1/102 (1%)
Frequent convulsions	0/51 (0%)		1/51 (2%)		1/102 (1%)
Skin and subcutaneous tissue disorders
Drug eruption	0/51 (0%)		1/51 (2%)		1/102 (1%)
Other (Not Including Serious) Adverse Events
	Adults: LTG		Adolescents: LTG		Total: LTG
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	48/51 (94.1%)		50/51 (98%)		98/102 (96.1%)
Gastrointestinal disorders
Diarrhoea	3/51 (5.9%)		11/51 (21.6%)		14/102 (13.7%)
Vomiting	4/51 (7.8%)		7/51 (13.7%)		11/102 (10.8%)
Constipation	3/51 (5.9%)		4/51 (7.8%)		7/102 (6.9%)
General disorders
Pyrexia	7/51 (13.7%)		6/51 (11.8%)		13/102 (12.7%)
Infections and infestations
Nasopharyngitis	10/51 (19.6%)		14/51 (27.5%)		24/102 (23.5%)
Pharyngitis	3/51 (5.9%)		2/51 (3.9%)		5/102 (4.9%)
Injury, poisoning and procedural complications
Contusion	8/51 (15.7%)		4/51 (7.8%)		12/102 (11.8%)
Arthropod sting	1/51 (2%)		9/51 (17.6%)		10/102 (9.8%)
Excoriation	6/51 (11.8%)		2/51 (3.9%)		8/102 (7.8%)
Nervous system disorders
Somnolence	7/51 (13.7%)		11/51 (21.6%)		18/102 (17.6%)
Dizziness	10/51 (19.6%)		2/51 (3.9%)		12/102 (11.8%)
Psychiatric disorders
Affect lability	1/51 (2%)		4/51 (7.8%)		5/102 (4.9%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation	5/51 (9.8%)		15/51 (29.4%)		20/102 (19.6%)
Rhinorrhoea	2/51 (3.9%)		3/51 (5.9%)		5/102 (4.9%)
Skin and subcutaneous tissue disorders
Erythema	1/51 (2%)		6/51 (11.8%)		7/102 (6.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.