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

• Sponsor: UCB BIOSCIENCES, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01118949
• Collaborator: (none)
• Enrollment: 49
• Locations: 25
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose is to assess the safety of Lacosamide in subjects with uncontrolled Primary Generalized Tonic-Clonic (PGTC) seizures with Idiopathic Generalized Epilepsy.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Lacosamide	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Pilot Study to Assess the Safety of Oral Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Aug 1, 2011
• Actual Study Completion Date: Aug 1, 2011

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Lacosamide

Drug: 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.; Other Names: Vimpat®

Outcome Measures

Primary Outcome Measures

1. Change in the Number of Seizure Days With Absence Seizures From the Baseline Phase to the Maintenance Phase [From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)]

   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.

2. Change in the Number of Seizure Days With Myoclonic Seizures From the Baseline Phase to the Maintenance Phase [From Baseline Phase (Weeks 0 to 4) to Maintenance Phase (Weeks 8 to 13)]

   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.

Secondary Outcome Measures

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

   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.

2. 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) [From Visit 2 (Week 4) to Visit 6 (Week 8)]

   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.

3. Number of Subjects With Treatment Emergent Adverse Events (TEAEs) During the 10-week Treatment Period [From Visit 2 (Week 4) to Visit 7 (Week 13)]

   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.

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

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 16 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject has a diagnosis of uncontrolled epilepsy with primary generalized tonic-clonic (PGTC) seizures and idiopathic generalized epilepsy. Diagnosis should have been established by an electroencephalogram (EEG) with generalized spike-wave discharges within 5 years of the screening visit

• Subject has ≥1 PGTC seizure within the 12 weeks prior to the screening visit

• Subject has a stable dose regimen of 1 to 3 marketed antiepileptic drug(s) (AEDs) with or without additional concurrent stable Vagus Nerve Stimulation (VNS). The VNS must have been in place for at least 6 months prior to study entry with constant settings for at least 28 days prior to the screening visit and during the Baseline Phase. Benzodiazepines will be counted as an AED

Exclusion Criteria:

• Subject has a history of partial-onset seizures or EEG findings consistent with partial onset seizures

• Subject has a history of status epilepticus within the 5-year Period prior to Visit 1

• Subject has a current or previous diagnosis of pseudoseizures, conversion disorders, or other non-epileptic ictal events

• Subject has any medical or psychiatric condition

• Subject has any history of alcohol or drug abuse

• Subject is currently taking felbamate

• Subject has ever taken vigabatrin and has no visual fields examination report available or if results of the examination are abnormal

• Subject is on a ketogenic diet

• Subject has a known sodium channelopathy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Alabaster	Alabama	United States
2		Phoenix	Arizona	United States
3		Little Rock	Arkansas	United States
4		San Francisco	California	United States
5		Aurora	Colorado	United States
6		Atlanta	Georgia	United States
7		Rome	Georgia	United States
8		Boise	Idaho	United States
9		Fort Wayne	Indiana	United States
10		Lexington	Kentucky	United States
11		Louisville	Kentucky	United States
12		Scarborough	Maine	United States
13		Bethesda	Maryland	United States
14		Chesterfield	Missouri	United States
15		New York	New York	United States
16		Columbus	Ohio	United States
17		Hershey	Pennsylvania	United States
18		Charleston	South Carolina	United States
19		Nashville	Tennessee	United States
20		Dallas	Texas	United States
21		Houston	Texas	United States
22		Charlottesville	Virginia	United States
23		Norfolk	Virginia	United States
24		Renton	Washington	United States
25		Madison	Wisconsin	United States

Sponsors and Collaborators

• UCB BIOSCIENCES, Inc.

Investigators

• Study Director: UCB Clinical Trial Call Center, [phone] (UCB)

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB BIOSCIENCES, Inc.
• ClinicalTrials.gov Identifier: NCT01118949
• Other Study ID Numbers: SP0961; 2014-004379-22
• First Posted: May 7, 2010
• Last Update Posted: Jul 17, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by UCB BIOSCIENCES, Inc.: Primary Generalized Tonic-Clonic (PGTC) Seizures; Absence Seizures; Myoclonic Seizures; Idiopathic Generalized Epilepsy (IGE)
• Additional relevant MeSH terms: Epilepsy; Seizures; Lacosamide

Study Results

Participant Flow

Recruitment Details	Safety Set (SS) includes all enrolled subjects who took at least 1 dose of Lacosamide (LCM).
Pre-assignment Detail	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

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 Participants	49
Age (Count of Participants)
<=18 years	3 6.1%
Between 18 and 65 years	46 93.9%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.7 (10.1)
Sex: Female, Male (Count of Participants)
Female	36 73.5%
Male	13 26.5%
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	168.08 (9.32)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	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.
Measure Participants	44
Mean (Standard Deviation) [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.
Measure Participants	44
Mean (Standard Deviation) [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.
Measure Participants	40
Mean (Standard Deviation) [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.
Measure Participants	40
Mean (Standard Deviation) [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.
Measure Participants	49
Number [participants]	43 87.8%

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.
Measure Participants	49
Number [participants]	5 10.2%

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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Lacosamide
	Affected / at Risk (%)	# Events
Total	1/49 (2%)
Nervous system disorders
Petit mal epilepsy	1/49 (2%)	1
Other (Not Including Serious) Adverse Events
	Lacosamide
	Affected / at Risk (%)	# Events
Total	39/49 (79.6%)
Eye disorders
Diplopia	4/49 (8.2%)	4
Gastrointestinal disorders
Nausea	13/49 (26.5%)	15
Vomiting	7/49 (14.3%)	9
General disorders
Fatigue	6/49 (12.2%)	6
Gait Disturbance	5/49 (10.2%)	5
Chills	4/49 (8.2%)	5
Injury, poisoning and procedural complications
Contusion	3/49 (6.1%)	4
Nervous system disorders
Dizziness	19/49 (38.8%)	27
Headache	8/49 (16.3%)	8
Somnolence	8/49 (16.3%)	8
Tremor	6/49 (12.2%)	8
Migraine	4/49 (8.2%)	4
Petit mal epilepsy	4/49 (8.2%)	4
Psychiatric disorders
Insomnia	6/49 (12.2%)	6
Respiratory, thoracic and mediastinal disorders
Dyspnea	4/49 (8.2%)	4
Skin and subcutaneous tissue disorders
Pruritus	3/49 (6.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.