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

• ClinicalTrials.gov Identifier: NCT01118949
• Recruitment Status: Completed
• First Posted: May 7, 2010
• Results First Posted: September 7, 2012
• Last Update Posted: July 17, 2018
• Sponsor: UCB BIOSCIENCES, Inc.
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES, Inc. )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsy
• Intervention: Drug: Lacosamide
• Enrollment: 49

Participant Flow

Recruitment Details	Safety Set (SS) includes all enrolled subjects who took at least 1 dose of Lacosamide (LCM).
Pre-assignment Details	Participant Flow and Baseline Characteristics refer to the Safety Set (SS).

Arm/Group Title	Lacosamide
Arm/Group Description	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.
Period Title: Overall Study
Started	49
Completed	40
Not Completed	9
Reason Not Completed
Adverse Event	5
Withdrawal by Subject	4

Baseline Characteristics

Arm/Group Title		Lacosamide
Arm/Group Description		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 Number of Baseline Participants		49
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	49 participants
	<=18 years	3 6.1%
	Between 18 and 65 years	46 93.9%
	>=65 years	0 0.0%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	49 participants
		29.7 (10.1)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	49 participants
	Female	36 73.5%
	Male	13 26.5%
Height; Mean (Standard Deviation); Unit of measure: Centimeter (cm)
	Number Analyzed	49 participants
		168.08 (9.32)
Weight; Mean (Standard Deviation); Unit of measure: Kilogram (kg)
	Number Analyzed	49 participants
		77.90 (19.80)

Outcome Measures

1. Primary Outcome

Title	Change in the Number of Seizure Days With Absence Seizures From the Baseline Phase to the Maintenance Phase
Description	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.
Time Frame	From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lacosamide
Arm/Group Description:	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 Number of Participants Analyzed	44
Mean (Standard Deviation); Unit of Measure: number of seizure days
	-0.37 (4.8)

2. Primary Outcome

Title	Change in the Number of Seizure Days With Myoclonic Seizures From the Baseline Phase to the Maintenance Phase
Description	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.
Time Frame	From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lacosamide
Arm/Group Description:	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 Number of Participants Analyzed	44
Mean (Standard Deviation); Unit of Measure: number of seizure days
	-2.19 (5.80)

3. Secondary Outcome

Title	Changes in Count of Generalized Spike-wave Discharges on 24-hour Ambulatory Electroencephalogram (EEG) From Visit 2 (Baseline Phase) to Visit 6 (Maintenance Phase)
Description	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.
Time Frame	From Visit 2 (Week 4) to Visit 6 (Week 8)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lacosamide
Arm/Group Description:	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 Number of Participants Analyzed	40
Mean (Standard Deviation); Unit of Measure: 1/hour
	-3.47 (55.85)

4. Secondary Outcome

Title	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)
Description	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.
Time Frame	From Visit 2 (Week 4) to Visit 6 (Week 8)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lacosamide
Arm/Group Description:	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 Number of Participants Analyzed	40
Mean (Standard Deviation); Unit of Measure: 1/hour
	0.13 (2.17)

5. Secondary Outcome

Title	Number of Subjects With Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period
Description	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.
Time Frame	From Visit 2 (Week 4) to Visit 7 (Week 13)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lacosamide
Arm/Group Description:	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 Number of Participants Analyzed	49
Measure Type: Number; Unit of Measure: participants
	43

6. Secondary Outcome

Title	Number of Subjects Withdrawn From the Study Due to Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period
Description	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.
Time Frame	From Visit 2 (Week 4) to Visit 7 (Week 13)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Lacosamide
Arm/Group Description:	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 Number of Participants Analyzed	49
Measure Type: Number; Unit of Measure: participants
	5

Adverse Events

Time Frame	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 Event Reporting Description	Adverse Events refer to the Safety Set (SS). SS includes all enrolled subjects who received at least one dose of trial medication.
Arm/Group Title	Lacosamide
Arm/Group Description	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.
All-Cause Mortality
	Lacosamide
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Lacosamide
	Affected / at Risk (%)	# Events
Total	1/49 (2.04%)
Nervous system disorders
Petit mal epilepsy * 1	1/49 (2.04%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (9.1)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Lacosamide
	Affected / at Risk (%)	# Events
Total	39/49 (79.59%)
Eye disorders
Diplopia * 1	4/49 (8.16%)	4
Gastrointestinal disorders
Nausea * 1	13/49 (26.53%)	15
Vomiting * 1	7/49 (14.29%)	9
General disorders
Fatigue * 1	6/49 (12.24%)	6
Gait Disturbance * 1	5/49 (10.20%)	5
Chills * 1	4/49 (8.16%)	5
Injury, poisoning and procedural complications
Contusion * 1	3/49 (6.12%)	4
Nervous system disorders
Dizziness * 1	19/49 (38.78%)	27
Headache * 1	8/49 (16.33%)	8
Somnolence * 1	8/49 (16.33%)	8
Tremor * 1	6/49 (12.24%)	8
Migraine * 1	4/49 (8.16%)	4
Petit mal epilepsy * 1	4/49 (8.16%)	4
Psychiatric disorders
Insomnia * 1	6/49 (12.24%)	6
Respiratory, thoracic and mediastinal disorders
Dyspnea * 1	4/49 (8.16%)	4
Skin and subcutaneous tissue disorders
Pruritus * 1	3/49 (6.12%)	3
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA (9.1)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: UCB Clinical Trial Call Center
• Organization: UCB
• Phone: +1 877 822 9493

Publications of Results:

Wechsler RT, Yates SL, Messenheimer J, Leroy R, Beller C, Doty P. Lacosamide for uncontrolled primary generalized tonic-clonic seizures: An open-label pilot study with 59-week extension. Epilepsy Res. 2017 Feb;130:13-20. doi: 10.1016/j.eplepsyres.2016.12.015. Epub 2016 Dec 29.

• Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
• ClinicalTrials.gov Identifier: NCT01118949
• Other Study ID Numbers: SP0961; 2014-004379-22 ( EudraCT Number )
• First Submitted: May 5, 2010
• First Posted: May 7, 2010
• Results First Submitted: August 8, 2012
• Results First Posted: September 7, 2012
• Last Update Posted: July 17, 2018