NCT00395694

Clinical Evaluation of BW430C in Epilepsy

Completed Phase 3 Results posted Last updated 26 September 2018

What this trial tests

Phase 3 trial testing lamictal in Epilepsy in 102 participants. Completed in 26 March 2009.

Timeline

7 August 2006

Primary endpoint
1 March 2009

26 March 2009

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	102
Start date	7 August 2006
Primary completion	1 March 2009
Estimated completion	26 March 2009
Sites	2 locations across Japan

Drugs / interventions tested

• lamictal (lamotrigine) — full drug profile →

Conditions studied

• Epilepsy — all drugs for Epilepsy →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

Adults 2 to 65, any sex, with Epilepsy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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.

Group	Value	95% CI
Adults: LTG	2
Adolescents: LTG	3
Total: LTG	5

Number of Rash Events Experienced (Including SJS and Any Other Serious Drug Eruption) During the Initial 8 Weeks of Study Treatment Secondary · 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.

Group	Value	95% CI
Adults: LTG	3
Adolescents: LTG	4
Total: LTG	7

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 Secondary · 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.

Severe

Group	Value	95% CI
Total: LTG	0

Moderate

Group	Value	95% CI
Total: LTG	2

Mild

Group	Value	95% CI
Total: LTG	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 Secondary · 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?".

Drug related

Group	Value	95% CI
Total: LTG	3

Not related to drug

Group	Value	95% CI
Total: LTG	4

Percentage of Participants With at Least a 50 Percent Reduction in Seizure Frequency for the Indicated Types of Seizures Secondary · 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.

All Partial Seizures, n=28, 25, 53

Group	Value	95% CI
Adults: LTG	17.9
Adolescents: LTG	20.0
Total: LTG	18.9

Tonic-clonic Seizures, n=5, 4, 9

Group	Value	95% CI
Adults: LTG	60.0
Adolescents: LTG	0
Total: LTG	33.3

Generalized Seizures with LGS, n=25, 25, 50

Group	Value	95% CI
Adults: LTG	16.0
Adolescents: LTG	20.0
Total: LTG	18.0

Percent Change in Seizure Frequency of the Indicated Types of Seizures Secondary · 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.

All Partial Seizures, n=28, 25, 53

Group	Value	95% CI
Adults: LTG	6.3	-44.8 – 28.7
Adolescents: LTG	-11.1	-46.6 – 34.6
Total: LTG	-9.8	-42.3 – 28.6

Tonic-clonic Seizures, n=5, 4, 9

Group	Value	95% CI
Adults: LTG	83.3	NA – NA
Adolescents: LTG	27.4	NA – NA
Total: LTG	36.5	-47.9 – 100.0

Generalized Seizures with LGS, n=25, 25, 50

Group	Value	95% CI
Adults: LTG	18.6	-16.2 – 32.2
Adolescents: LTG	10.1	-24.9 – 28.8
Total: LTG	12.4	5.8 – 27.6

Number of Participants With Any Rash Event (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase Secondary · 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.

Group	Value	95% CI
Adults: LTG	2
Adolescents: LTG	3
Total: LTG	5

Number of Rash Events Experienced (Including SJS and Any Other Serious Drug Eruption) up to the End of the Maintenance Phase Secondary · 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.

Group	Value	95% CI
Adults: LTG	3
Adolescents: LTG	4
Total: LTG	7

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 Secondary · 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.

Severe

Group	Value	95% CI
Total: LTG	0

Moderate

Group	Value	95% CI
Total: LTG	2

Mild

Group	Value	95% CI
Total: LTG	3

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 Secondary · 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?".

Drug related

Group	Value	95% CI
Total: LTG	3

Not related to drug

Group	Value	95% CI
Total: LTG	4

Number of Rash Events (Including SJS and Any Other Serious Drug Eruption) Adjudicated by the Rash Adjudication Committee in Participants Taking VPA Secondary · 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.

Group	Value	95% CI
Adults: LTG	1
Adolescents: LTG	2
Total: LTG	3

Percentage of Participants With Monocyte Values Outside the Normal Range (Shifted High) at Weeks 4 and 8 Secondary · 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

Week 4

Group	Value	95% CI
Total: LTG	15.2

Week 8

Group	Value	95% CI
Total: LTG	16.2

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Adults: LTG

Serious: 5/51 (10%)

Deaths: —

Adolescents: LTG

Serious: 2/51 (4%)

Deaths: —

Total: LTG

Serious: 7/102 (7%)

Deaths: —

Serious adverse events (8 terms)

Reaction	System	Adults: LTG	Adolescents: LTG	Total: LTG
Sleepiness	Nervous system disorders	—	—	—
Pyrexia	General disorders	—	—	—
Drug eruption	Skin and subcutaneous tissue disorders	—	—	—
Status epilepticus	Nervous system disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Aleviatin (phenytoin) poisoning	Injury, poisoning and procedural complications	—	—	—
Frequent convulsions	Nervous system disorders	—	—	—

Other adverse events (15 terms — click to expand)

Reaction	System	Adults: LTG	Adolescents: LTG	Total: LTG
Nasopharyngitis	Infections and infestations	—	—	—
Upper respiratory tract inflammation	Respiratory, thoracic and mediastinal disorders	—	—	—
Somnolence	Nervous system disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Pyrexia	General disorders	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—
Dizziness	Nervous system disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Arthropod sting	Injury, poisoning and procedural complications	—	—	—
Excoriation	Injury, poisoning and procedural complications	—	—	—
Erythema	Skin and subcutaneous tissue disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Pharyngitis	Infections and infestations	—	—	—
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Affect lability	Psychiatric disorders	—	—	—

Most-reported serious reactions: Sleepiness, Pyrexia, Drug eruption, Status epilepticus, Pneumonia, Vomiting, Aleviatin (phenytoin) poisoning, Frequent convulsions.

Data from ClinicalTrials.gov NCT00395694 adverse events section.

Sponsor's own description

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

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Epilepsy Characteristics in Neurodevelopmental Disorders: Research from Patient Cohorts and Animal Models Focusing on Autism Spectrum Disorder.
   Chakraborty S, Parayil R, Mishra S, Nongthomba U, et al · · 2022 · cited 18× · PMID 36142719 · DOI 10.3390/ijms231810807