Trial Outcomes & Findings for Open-Label Study to Assess Lacosamide Safety as Add-on Therapy for Primary Generalized Tonic-Clonic Seizures in Subjects With Epilepsy (NCT NCT01118949)

Last Updated: 2018-07-17

Results Overview

During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded: * Seizure type * Seizure frequency A negative value in change of seizure days with absence seizures shows a decrease in seizure days with absence seizures.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)

Results posted on

2018-07-17

Participant Flow

Safety Set (SS) includes all enrolled subjects who took at least 1 dose of Lacosamide (LCM).

Participant Flow and Baseline Characteristics refer to the Safety Set (SS).

Participant milestones

Participant milestones
Measure	Lacosamide Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Overall Study STARTED	49
Overall Study COMPLETED	40
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Lacosamide Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Overall Study Adverse Event	5
Overall Study Withdrawal by Subject	4

Baseline Characteristics

Open-Label Study to Assess Lacosamide Safety as Add-on Therapy for Primary Generalized Tonic-Clonic Seizures in Subjects With Epilepsy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lacosamide n=49 Participants Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Age, Categorical <=18 years	3 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	46 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	29.7 years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants
Sex: Female, Male Male	13 Participants n=5 Participants
Height	168.08 centimeter (cm) STANDARD_DEVIATION 9.32 • n=5 Participants
Weight	77.90 kilogram (kg) STANDARD_DEVIATION 19.80 • n=5 Participants

PRIMARY outcome

Timeframe: From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)

Population: Of the 49 subjects in the Safety Set (SS), 44 are included in this analysis. Data not available for 5 subjects.

Outcome measures

Outcome measures
Measure	Lacosamide n=44 Participants Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Change in the Number of Seizure Days With Absence Seizures From the Baseline Phase to the Maintenance Phase	-0.37 number of seizure days Standard Deviation 4.8

PRIMARY outcome

Timeframe: From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)

Population: Of the 49 subjects in the Safety Set (SS), 44 are included in this analysis. Data not available for 5 subjects.

During the study subjects kept a diary to record daily seizure activity from Visit 1 until the end of study participation. The following information has been recorded: * Seizure type * Seizure frequency A negative value in change of seizure days with myoclonic seizures shows a decrease in seizure days with myoclonic seizures.

Outcome measures

Outcome measures
Measure	Lacosamide n=44 Participants Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Change in the Number of Seizure Days With Myoclonic Seizures From the Baseline Phase to the Maintenance Phase	-2.19 number of seizure days Standard Deviation 5.80

SECONDARY outcome

Timeframe: From Visit 2 (Week 4) to Visit 6 (Week 8)

Population: Of the 49 subjects in the Safety Set (SS), 40 subjects are included in this analysis. Data not available for 9 subjects.

Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with \> 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The general spike-wave discharges are calculated per interpretable hours.

Outcome measures

Outcome measures
Measure	Lacosamide n=40 Participants Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase)	-3.47 1/hour Standard Deviation 55.85

SECONDARY outcome

Timeframe: From Visit 2 (Week 4) to Visit 6 (Week 8)

Population: Of the 49 subjects in the Safety Set (SS), 40 subjects are included in this analysis. Data not available for 9 subjects.

Subjects were asked to return to the clinic on the morning of the day prior to Visit 2 and Visit 6 to begin 24-hour ambulatory EEG recordings for evaluation of spike-wave discharges. Only subjects with an evaluable EEG measurement with \> 19 interpretable hours at Visit 2 and Visit 6 are included in this analysis. The 3 Hertz (Hz) spike-wave discharges are calculated per awake hours.

Outcome measures

Outcome measures
Measure	Lacosamide n=40 Participants Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Changes in Count of 3 Hertz (Hz) Spike-wave Discharges (During Waking Hours) on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase)	0.13 1/hour Standard Deviation 2.17

SECONDARY outcome

Timeframe: From Visit 2 (Week 4) to Visit 7 (Week 13)

Population: All 49 subjects in the Safety Set (SS) are included in this analysis.

An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment.

Outcome measures

Outcome measures
Measure	Lacosamide n=49 Participants Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period	43 participants

SECONDARY outcome

Timeframe: From Visit 2 (Week 4) to Visit 7 (Week 13)

Population: All 49 subjects in the Safety Set (SS) are included in this analysis.

Outcome measures

Outcome measures
Measure	Lacosamide n=49 Participants Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Number of Subjects Withdrawn From the Study Due to Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period	5 participants

Adverse Events

Lacosamide

Serious events: 1 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lacosamide n=49 participants at risk Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Nervous system disorders Petit mal epilepsy	2.0% 1/49 • Number of events 1 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.

Other adverse events

Other adverse events
Measure	Lacosamide n=49 participants at risk Lacosamide is supplied as 50 mg, 100 mg, 150 mg, and 200 mg tablets. Subjects will begin a Dose-Titration Phase of Lacosamide at 100 mg/day (50 mg bid, approx. 12 hours apart, once in the morning and once in the evening) for 1 week. Three (3) weekly increases will follow until the subject reaches a dosage of 200 mg/day, 300 mg/day, or 400 mg/day, as deemed clinically appropriate. The final titration will be followed by a 6-week Maintenance Phase. Subjects who complete the Maintenance Phase have the opportunity to enroll in an open-label extension study; those who do not enroll will begin a 3-week End-of-Study Phase when Lacosamide will be tapered off gradually at a recommended rate of 200 mg/day/week.
Eye disorders Diplopia	8.2% 4/49 • Number of events 4 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Gastrointestinal disorders Nausea	26.5% 13/49 • Number of events 15 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Gastrointestinal disorders Vomiting	14.3% 7/49 • Number of events 9 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
General disorders Fatigue	12.2% 6/49 • Number of events 6 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
General disorders Gait Disturbance	10.2% 5/49 • Number of events 5 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
General disorders Chills	8.2% 4/49 • Number of events 5 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Injury, poisoning and procedural complications Contusion	6.1% 3/49 • Number of events 4 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Nervous system disorders Dizziness	38.8% 19/49 • Number of events 27 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Nervous system disorders Headache	16.3% 8/49 • Number of events 8 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Nervous system disorders Somnolence	16.3% 8/49 • Number of events 8 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Nervous system disorders Tremor	12.2% 6/49 • Number of events 8 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Nervous system disorders Migraine	8.2% 4/49 • Number of events 4 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Nervous system disorders Petit mal epilepsy	8.2% 4/49 • Number of events 4 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Psychiatric disorders Insomnia	12.2% 6/49 • Number of events 6 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Respiratory, thoracic and mediastinal disorders Dyspnea	8.2% 4/49 • Number of events 4 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Skin and subcutaneous tissue disorders Pruritus	6.1% 3/49 • Number of events 3 • Adverse Events were collected up to 16 weeks from Baseline (Week 0 - Week 4) over the 3-weeks Titration Period (Week 4 - Week 7) and the 6-weeks Maintenance Period (Week 7 - Week 13) to the Final Clinic Visit at the end of Week 16. Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.

Additional Information

UCB Clinical Trial Call Center

UCB

Phone: +1 877 822 9493

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60