Trial to Assess Lacosamide as the First add-on Anti-epileptic Drug Treatment in Patients With Partial-onset Seizures

• ClinicalTrials.gov Identifier: NCT00955357
• Recruitment Status: Completed
• First Posted: August 10, 2009
• Results First Posted: May 1, 2014
• Last Update Posted: July 17, 2018
• Sponsor: UCB Pharma
• Information provided by (Responsible Party): UCB Pharma

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Partial Epilepsies
• Intervention: Drug: Lacosamide
• Enrollment: 461

Participant Flow

Recruitment Details	An estimated 656 subjects were to be enrolled in the study at approximately 130 sites in the US, Europe, and the rest of the world.
Pre-assignment Details	Overall 461 subjects were enrolled. The Participant Flow refers to the Safety Set (SS) which was defined as all enrolled subjects who took at least 1 dose of Lacosamide. Reasons for discontinuation were only calculated for the SS. 456 subjects were included in the Safety Set.

Arm/Group Title	First Add-on	Later Add-on
Arm/Group Description	Lacosamide added to first adequate monotherapy (no history of Anti-Epileptic Drug [AED] polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week	Lacosamide added to 1 to 3 Anti-Epileptic Drugs (AEDs) (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
Period Title: Titration Phase
Started	96	360
Completed	80	294
Not Completed	16	66
Reason Not Completed
Adverse Event	9	46
Lack of Efficacy	0	2
Protocol Violation	3	7
Lost to Follow-up	1	3
Withdrawal by Subject	3	5
Prohibited Antiepileptic Drug change	0	1
Study medication not tolerated	0	1
Non compliance to study procedures	0	1
Period Title: Maintenance Phase
Started	80	294
Completed	68	249
Not Completed	12	45
Reason Not Completed
Adverse Event	3	23
Lack of Efficacy	0	4
Protocol Violation	2	6
Lost to Follow-up	2	7
Withdrawal by Subject	4	4
Patient moving out of area	0	1
Non compliance to study procedures	1	0

Baseline Characteristics

Arm/Group Title		First Add-on	Later-Add-on	Total
Arm/Group Description		Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week	Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week	Total of all reporting groups
Overall Number of Baseline Participants		96	360	456
Baseline Analysis Population Description		The Baseline Analysis Population refers to the Safety Set (SS) which includes all enrolled subjects who took at least one dose of study medication. 5 subjects at one site were excluded from the Safety Set due to significant study conduct deficiencies.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	96 participants	360 participants	456 participants
		37.5; (18.0 to 82.0)	38.0; (16.0 to 74.0)	38.0; (16.0 to 82.0)
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	96 participants	360 participants	456 participants
	<=18 years	4 4.2%	7 1.9%	11 2.4%
	Between 18 and 65 years	82 85.4%	349 96.9%	431 94.5%
	>=65 years	10 10.4%	4 1.1%	14 3.1%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	96 participants	360 participants	456 participants
	Female	53 55.2%	180 50.0%	233 51.1%
	Male	43 44.8%	180 50.0%	223 48.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	96 participants	360 participants	456 participants
	American Indian or Alaska Native	11 11.5%	6 1.7%	17 3.7%
	Asian	0 0.0%	12 3.3%	12 2.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 1.0%	19 5.3%	20 4.4%
	White	79 82.3%	278 77.2%	357 78.3%
	More than one race	5 5.2%	45 12.5%	50 11.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	96 participants	360 participants	456 participants
	Hispanic or Latino	24 25.0%	99 27.5%	123 27.0%
	Not Hispanic or Latino	72 75.0%	261 72.5%	333 73.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Weight; Median (Full Range); Unit of measure: Kilogram
	Number Analyzed	96 participants	360 participants	456 participants
		71.8; (42.0 to 132.9)	73.0; (41.9 to 147.4)	73.0; (41.9 to 147.4)
Height; Median (Full Range); Unit of measure: Centimeter
	Number Analyzed	96 participants	360 participants	456 participants
		166.5; (149.0 to 186.0)	167.6; (140.0 to 197.0)	167.6; (140.0 to 197.0)
BMI; Median (Full Range); Unit of measure: Kilogram per m^2
	Number Analyzed	96 participants	360 participants	456 participants
		25.3; (14.5 to 42.5)	25.5; (17.3 to 53.9)	25.4; (14.5 to 53.9)

Outcome Measures

1. Primary Outcome

Title	The Proportion of Subjects Who Achieved "Seizure-free Status" During the First 12 Weeks of the Maintenance Phase
Description	A subject will be considered seizure-free if the subject completes the first 12 weeks of the Maintenance Phase, reports zero seizures, and has no seizure data missing for any day during the period of time. This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.
Time Frame	From Week 7 (end of Week 6) to end of Week 18

Outcome Measure Data

Analysis Population Description

The Analysis Population refers to the Completer Set (CS) which includes all subjects who were enrolled, received at least one dose of Lacosamide and completed the first 12 weeks of the Maintenance Phase.

Arm/Group Title	First Add-on	Later Add-on
Arm/Group Description:	Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week	Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
Overall Number of Participants Analyzed	72	261
Measure Type: Number; Unit of Measure: percentage of subjects
	37.5	14.9

Adverse Events

Time Frame	Treatment Emergent Adverse Events were collected from Screening (Week -1) until the end of the study ( up to Week 33).
Adverse Event Reporting Description	Treatment Emergent Adverse Events started on/after the date of first dose and within 30 days of the date of last dose.
Arm/Group Title	First Add-on		Later Add-on
Arm/Group Description	Lacosamide added to first adequate monotherapy (no history of AED polytherapy) and epilepsy diagnosis < or = 24 months at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week		Lacosamide added to 1 to 3 AEDs (with tentatives of at least 2 prior AED treatment regimens) and epilepsy diagnosis > or = 5 years at Screening. Lacosamide: oral tablet Subjects Titration Phase (6 Weeks): Week 1 - 50 mg tablet Twice daily (bid); Week 2 - 100 mg tablet bid; Week 3 - 150 mg tablet bid; Week 4 - 200 mg tablet bid; Week 5 - 200 mg tablet bid; Week 6 - 150 mg tablet bid OR Week 6 - 200 mg tablet bid Maintenance Phase (24 Weeks): 200 mg tablet bid OR 150 mg tablet bid Taper Phase (1 - 3 Weeks): 50 mg tablet bid for 1 week OR 100 mg tablet bid for 1 week OR 150 mg tablet bid for 1 week
All-Cause Mortality
	First Add-on		Later Add-on
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	First Add-on		Later Add-on
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/96 (8.33%)		19/360 (5.28%)
Blood and lymphatic system disorders
Agranulocytosis * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Cardiac disorders
Angina pectoris * 1	1/96 (1.04%)	1	0/360 (0.00%)	0
Eye disorders
Diplopia * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
General disorders
Pyrexia * 1	0/96 (0.00%)	0	2/360 (0.56%)	2
Chest discomfort * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Infections and infestations
Pneumonia * 1	1/96 (1.04%)	1	0/360 (0.00%)	0
Tooth abscess * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Urinary tract infection * 1	1/96 (1.04%)	1	0/360 (0.00%)	0
Injury, poisoning and procedural complications
Arthropod bite * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Femoral neck fracture * 1	1/96 (1.04%)	1	0/360 (0.00%)	0
Hip fracture * 1	1/96 (1.04%)	1	0/360 (0.00%)	0
Humerus fracture * 1	1/96 (1.04%)	1	0/360 (0.00%)	0
Joint dislocation * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Subdural haematoma * 1	1/96 (1.04%)	1	0/360 (0.00%)	0
Investigations
Electrocardiogram ST segment elevation * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Metabolism and nutrition disorders
Hypochloraemia * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Hyponatraemia * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Nervous system disorders
Convulsion * 1	2/96 (2.08%)	2	2/360 (0.56%)	2
Dizziness * 1	0/96 (0.00%)	0	2/360 (0.56%)	2
Complex partial seizures * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Coordination abnormal * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Dysarthria * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Dyskinesia * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Epilepsy * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Grand mal convulsion * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Headache * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Lacunar infarction * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Partial seizures with secondary generalisation * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Psychiatric disorders
Panic attack * 1	0/96 (0.00%)	0	1/360 (0.28%)	1
Suicide attempt * 1	1/96 (1.04%)	1	0/360 (0.00%)	0
Surgical and medical procedures
Abortion induced * 1	1/96 (1.04%)	1	1/360 (0.28%)	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%
	First Add-on		Later Add-on
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/96 (55.21%)		212/360 (58.89%)
Ear and labyrinth disorders
Vertigo * 1	9/96 (9.38%)	11	22/360 (6.11%)	22
Eye disorders
Vision blurred * 1	2/96 (2.08%)	3	24/360 (6.67%)	28
Diplopia * 1	7/96 (7.29%)	7	17/360 (4.72%)	17
Gastrointestinal disorders
Nausea * 1	8/96 (8.33%)	8	24/360 (6.67%)	27
Infections and infestations
Influenza * 1	5/96 (5.21%)	5	4/360 (1.11%)	4
Nervous system disorders
Dizziness * 1	30/96 (31.25%)	37	119/360 (33.06%)	159
Somnolence * 1	6/96 (6.25%)	8	54/360 (15.00%)	65
Headache * 1	13/96 (13.54%)	19	41/360 (11.39%)	57
Tremor * 1	3/96 (3.13%)	3	22/360 (6.11%)	23
Psychiatric disorders
Anxiety * 1	6/96 (6.25%)	6	4/360 (1.11%)	4
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 9.1

Limitations and Caveats

This study was intended to assess the efficacy outcomes in the First Add-On Group and the Later Add-On Group individually relative to historical data. Comparisons between the 2 groups should not be attempted and conclusions should not be drawn.

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

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT00955357
• Other Study ID Numbers: SP0954; 2009-011181-28 ( EudraCT Number )
• First Submitted: August 6, 2009
• First Posted: August 10, 2009
• Results First Submitted: March 28, 2014
• Results First Posted: May 1, 2014
• Last Update Posted: July 17, 2018