Study to Investigate Lacosamide as Add-on Therapy in Subjects ≥4 Years to <17 Years of Age With Partial Onset Seizures

• Sponsor: UCB Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01921205
• Collaborator: (none)
• Enrollment: 404
• Locations: 118
• Arms: 2
• Duration (Months): 40.9
• Patients Per Site: 3.4
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Study to evaluate the efficacy of Lacosamide (LCM) administered in addition to 1 to ≤3 other Anti-Epileptic Drugs in subjects with epilepsy ≥4 years to <17 years of age who currently have uncontrolled partial onset seizures.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy	Drug: Lacosamide; Other: Placebo	Phase 3

Detailed Description

The primary objective of this study is to evaluate the efficacy of LCM administered concomitantly with 1 to ≤3 Anti-Epileptic Drugs (AEDs) in subjects with epilepsy ≥4 years to <17 years of age who currently have uncontrolled partial onset seizures.

The secondary objective is to evaluate the safety and tolerability of LCM in subjects ≥4 years to <17 years of age.

An additional objective is to evaluate the pharmacokinetics (PK) of LCM in subjects ≥4 years to <17 years of age.

Study Design

• Study Type: Interventional
• Actual Enrollment: 404 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double Blind, Randomized, Placebo Controlled, Parallel Group Study to Investigate the Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects With Epilepsy ≥4 Years to <17 Years of Age With Partial Onset Seizures
• Study Start Date: Aug 29, 2013
• Actual Primary Completion Date: Jan 24, 2017
• Actual Study Completion Date: Jan 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lacosamide	Drug: Lacosamide; Subjects <30 kg (LCM oral solution): 4 mg/kg - 6 mg/kg BID ( 8mg/kg/day - 12 mg/kg/day) Subjects ≥30 kg to <50 kg (LCM oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day) Subjects ≥50 kg (LCM tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day); Other Names: Vimpat(R)
Placebo Comparator: Placebo	Other: Placebo; Subjects <30 kg (placebo oral solution): 4 mg/kg - 6 mg/kg BID (8 mg/kg/day - 12 mg/kg/day) Subjects ≥30 kg to <50 kg (placebo oral solution): 3 mg/kg - 4 mg/kg BID (6 mg/kg/day - 8 mg/kg/day) Subjects ≥50 kg (placebo tablets): 150 mg - 200 mg BID (300 mg/day - 400 mg/day)

Outcome Measures

Primary Outcome Measures

1. Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period [Baseline to Week 16 (or last value on treatment)]

   The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

Secondary Outcome Measures

1. Proportion of Responders Where a Responder is Defined as a Participant With >= 50% Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period [Baseline to Week 16 (or last value on treatment)]

   Proportion of responders is presented as percentage of participants. A responder is a subject experiencing a 50 % or greater reduction in partial onset seizure frequency per 28 days from Baseline to the Maintenance Period.

2. Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period [Baseline to Week 16 (or last value on treatment)]

   Proportion of subjects is presented as percentage of participants. A >=25%-<50% response in the Maintenance Period is defined as >=25% to <50% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A >=50%-<=75% response in the Maintenance Period is defined as >=50% to <=75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A 75% response in the Maintenance Period is defined as >75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period.

3. Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) [Baseline to Week 16 (or last value on treatment)]

   The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

4. Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) [Baseline to Week 16 (or last value on treatment)]

   Proportion of subjects is presented as percentage of participants. A >=25%-<50% response in the Treatment Period is defined as >=25% to <50% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A >=50%-<=75% response in the Treatment Period is defined as >=50% to <=75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A 75% response in the Treatment Period is defined as >75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period.

5. Proportion of Subjects Experiencing no Change in Partial Onset Seizure Frequency (Between <25 % Reduction and <25 % Increase) Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) [Baseline to Week 16 (or last value on treatment)]

   Proportion of subjects is presented as percentage of participants. No change is defined as between <25% reduction and <25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise not between <25% reduction and <25% increase is defined as a change.

6. Proportion of Subjects Experiencing an Increase in Partial Onset Seizure Frequency Per 28 Days of >=25 % From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) [Baseline to Week 16 (or last value on treatment)]

   Proportion of subjects is presented as percentage of participants. An increase is defined as a >=25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise <25% increase is defined as no increase.

7. Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures [Baseline to Week 16 (or last value on treatment)]

   The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

8. Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures [Baseline to Week 16 (or last value on treatment)]

   The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

9. Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures [Baseline to Week 16 (or last value on treatment)]

   The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.

10. Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period [Week 7 to Week 16]

    The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded.

11. Proportion of Subjects Who Achieved "Seizure Free" Status (Yes/no) for Subjects Who Completed the Maintenance Period [Week 7 to Week 16]

    The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written Informed Consent form is signed and dated by the parent(s) or legal representative. The Informed Consent form or a specific Assent form, where required, will be signed and dated by minors

• Subject/legal representative is considered reliable and capable of adhering to the protocol (eg, able to understand and complete diaries), visit schedule, and medication intake according to the judgment of the investigator

• Subject is male or female from ≥4 years to <17 years of age

• Subject has a diagnosis of Epilepsy with partial-onset seizures. The results of ≥1 prior electroencephalogram (EEG) AND 1 prior magnetic resonance imaging/computerized tomography scan should be consistent with the above diagnosis

• Subject has been observed to have uncontrolled partial-onset seizures after an adequate course of treatment (in the opinion of the investigator) with ≥2 Anti-Epileptic Drugs (AEDs) (concurrently or sequentially)

• Subject must have been observed to have on average ≥2 partial onset seizures per 28 days with seizure free phase no longer than 21 days in the 8 week period prior to entry into the Baseline Period. During this study, subjects must have reported ≥2 partial onset seizures during the 8 week prospective Baseline Period to be eligible for randomization at Visit 2. (Note: In the case of simple partial onset seizures, only those seizures with motor signs will be counted towards meeting the inclusion criterion.)

• Subject is on a stable dosage regimen of 1 to ≤3 AEDs. The daily dosage regimen of concomitant AED therapy must be kept constant for a period of ≥4 weeks prior to the Baseline Period

• Vagal nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED. The VNS device must be implanted for ≥6 months before Visit 1, and the device settings must be stable for ≥4 weeks before Visit 1 and be kept stable during the Baseline Period. Use of the VNS device magnet is allowed

Exclusion Criteria:

• Subject has previously participated in this study or subject has been assigned to Lacosamide (LCM) in a previous LCM study

• Subject has participated in another study of an investigational medicinal product (IMP) or a medical device within ≤2 months of Visit 1 or is currently participating in another study of an IMP or a medical device

• Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study

• Subject ≥6 years of age has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia Suicide Severity Rating Scale (C SSRS) at Screening

• Subject has a known hypersensitivity to any component of the IMP or has ever received LCM

• Female subject who is pregnant or nursing, and/or a female subject of childbearing potential who is not surgically sterile or does not practice 1 highly effective method of contraception (according to International Conference on Harmonisation [ICH] guidance defined as those that result in a failure rate of less than 1% per year when used consistently and correctly), unless sexually abstinent, for the duration of the study. Female subject of childbearing potential taking enzyme inducing antiepileptic drugs (EI AEDs: carbamazepine, phenytoin, barbiturates, primidone, topiramate, oxcarbazepine) who is not surgically sterile or does not practice 1 highly effective method of contraception according to the WHO recommendation (ie, depot medroxyprogesterone acetate, norethisterone enantate, intrauterine devices, combined injectables, and progestogen implants) with administration of EI AEDs OR does not practice 2 combined methods of contraception (ie, combined hormonal contraception plus barrier method with spermicidal agent), unless sexually abstinent, for the duration of the study

• Subject has a medical condition that could be expected in the opinion of the investigator to interfere with drug absorption, distribution, metabolism, or excretion

• Subject has experienced febrile seizures exclusively. The occurrence of febrile seizures in addition to other unprovoked seizures is not exclusionary

• Subject is on a ketogenic or other specialized diet. If the subject was on a specialized diet in the past, they must be off the diet for ≥2 months prior to the Baseline Period

• Subject has an alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin level ≥2 times the upper limit of normal (ULN), or creatinine clearance less than 30 mL/min

• Subject has a clinically relevant ECG abnormality, in the opinion of the investigator (eg, second or third degree heart block at rest or a corrected QT interval [QTc] greater than 450 ms)

• Subject has hemodynamically significant congenital heart disease

• Subject has an arrhythmic heart condition requiring medical therapy

• Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias

• Subject has nonepileptic events that could be confused with seizures

• Subject has a current diagnosis of Lennox-Gastaut syndrome, primary generalized epilepsy, mixed seizure disorder (partial and primarily generalized seizures), or purely nocturnal seizures

• Subject has a history of convulsive status epilepticus ≤2 months prior to the Baseline Period

• Subject has been treated with vigabatrin and experienced any vision loss. Subjects who have received vigabatrin in the past must have documentation of an assessment for vision loss prior to study entry or documentation of why visual field testing cannot be performed

• Subject has been treated with felbamate and has experienced any serious toxicity issues (defined as liver failure, aplastic anemia) with this treatment. Subjects treated with felbamate for <12 months are excluded. Note: any subject who has been treated with felbamate for ≥12 months and has not experienced serious toxicity issues is eligible

• Subject has a medically documented history of alcohol or drug abuse

• Subject has a known cardiac sodium channelopathy, such as Brugada syndrome

• Subject has an acute or sub acutely progressive central nervous system disease. Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease (malignant brain tumor or Rasmussen Syndrome)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	127	Boulder	Colorado	United States
2	105	Orlando	Florida	United States
3	117	Tampa	Florida	United States
4	103	Atlanta	Georgia	United States
5	124	Lexington	Kentucky	United States
6	112	Louisville	Kentucky	United States
7	121	Shreveport	Louisiana	United States
8	115	Las Vegas	Nevada	United States
9	102	Charlotte	North Carolina	United States
10	640	Eugene	Oregon	United States
11	122	Dallas	Texas	United States
12	101	Tomball	Texas	United States
13	114	Seattle	Washington	United States
14	143	Buenos Aires		Argentina
15	142	Cordoba		Argentina
16	200	Heidelberg West		Australia
17	203	Herston		Australia
18	205	South Brisbane		Australia
19	304	Brussels		Belgium
20	310	Sofia		Bulgaria
21	312	Sofia		Bulgaria
22	172	Floridablanca		Colombia
23	171	Medellin		Colombia
24	613	Osijek		Croatia
25	610	Rijeka		Croatia
26	612	Zagreb		Croatia
27	321	Hradec Kralove		Czechia
28	320	Ostrava-Poruba		Czechia
29	322	Praha 4		Czechia
30	323	Praha 5		Czechia
31	331	Tallinn		Estonia
32	330	Tartu		Estonia
33	620	Tbilisi		Georgia
34	621	Tbilisi		Georgia
35	622	Tbilisi		Georgia
36	623	Tbilisi		Georgia
37	361	Budapest		Hungary
38	362	Budapest		Hungary
39	363	Budapest		Hungary
40	364	Budapest		Hungary
41	360	Debrecen		Hungary
42	367	Miskolc		Hungary
43	366	Pecs		Hungary
44	370	Holon		Israel
45	371	Kfar Saba		Israel
46	374	Petach Tikva		Israel
47	372	Tel Aviv		Israel
48	384	Bologna		Italy
49	388	Florence		Italy
50	387	Genova		Italy
51	380	Mantova		Italy
52	381	Milano		Italy
53	393	Padova		Italy
54	383	Roma		Italy
55	392	Roma		Italy
56	386	Verona		Italy
57	211	Daegu		Korea, Republic of
58	210	Seoul		Korea, Republic of
59	212	Seoul		Korea, Republic of
60	213	Seoul		Korea, Republic of
61	215	Seoul		Korea, Republic of
62	400	Riga		Latvia
63	402	Valmiera		Latvia
64	411	Kaunas		Lithuania
65	569	Culiacan		Mexico
66	563	Guadalajara		Mexico
67	568	Monterrey		Mexico
68	660	Podgorica		Montenegro
69	433	Gdansk		Poland
70	432	Katowice		Poland
71	420	Kielce		Poland
72	422	Krakow		Poland
73	431	Krakow		Poland
74	423	Poznan		Poland
75	425	Poznan		Poland
76	421	Szczecin		Poland
77	429	Tyniec Maly		Poland
78	430	Warszawa		Poland
79	428	Wroclaw		Poland
80	574	Bucuresti		Romania
81	572	Cluj-Napoca		Romania
82	576	Sibiu		Romania
83	580	Suceava		Romania
84	570	Timisoara		Romania
85	577	Timisoara		Romania
86	443	Kazan		Russian Federation
87	444	Kazan		Russian Federation
88	442	Moscow		Russian Federation
89	449	Moscow		Russian Federation
90	440	Smolensk		Russian Federation
91	441	St. Petersburg		Russian Federation
92	446	St. Petersburg		Russian Federation
93	447	Voronezh		Russian Federation
94	464	Belgrade		Serbia
95	460	Kragujevac		Serbia
96	461	Novi Beograd		Serbia
97	462	Novi Sad		Serbia
98	463	Novi Sad		Serbia
99	470	Bardejov		Slovakia
100	473	Nitra		Slovakia
101	472	Nove Zamky		Slovakia
102	670	Ljubljana		Slovenia
103	220	Changhua		Taiwan
104	222	Taichung		Taiwan
105	224	Taipei		Taiwan
106	236	Bangkoknoi		Thailand
107	232	Bangkok		Thailand
108	231	Muang		Thailand
109	233	Muang		Thailand
110	235	Pathumwan		Thailand
111	230	Ratchathewi		Thailand
112	602	Dnipropetrovsk		Ukraine
113	606	Kiev		Ukraine
114	682	Uzhgorod		Ukraine
115	603	Vinnitsa		Ukraine
116	514	Birmingham		United Kingdom
117	515	Birmingham		United Kingdom
118	511	Leeds		United Kingdom

Sponsors and Collaborators

• UCB Pharma

Investigators

• Study Director: UCB Cares, [phone]

Study Documents (Full-Text)

• Statistical Analysis Plan - Feb 9, 2017
• Study Protocol - Mar 5, 2015

More Information

Additional Information:

• Product Information
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: UCB Pharma
• ClinicalTrials.gov Identifier: NCT01921205
• Other Study ID Numbers: SP0969; 2012-004996-38
• First Posted: Aug 13, 2013
• Last Update Posted: Jul 18, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by UCB Pharma: Lacosamide; Vimpat; UCB; Epilepsy; Partial Onset Seizures; Pediatric
• Additional relevant MeSH terms: Epilepsy; Seizures; Lacosamide

Study Results

Participant Flow

Recruitment Details	The study started to enroll patients in August 2013 and concluded in January 2017.
Pre-assignment Detail	The Participant Flow refers to the Safety Set which included all randomized subjects who took at least 1 dose of study medication.

Arm/Group Title	Placebo	Lacosamide
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Period Title: Overall Study
STARTED	172	171
COMPLETED	151	151
NOT COMPLETED	21	20

Baseline Characteristics

Arm/Group Title	Placebo	Lacosamide	Total Title
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Overall Participants	172	171	343
Age (Count of Participants)
<=18 years	172 100%	171 100%	343 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.9 (3.5)	10.5 (3.6)	10.7 (3.5)
Sex: Female, Male (Count of Participants)
Female	73 42.4%	80 46.8%	153 44.6%
Male	99 57.6%	91 53.2%	190 55.4%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 0.6%	0 0%	1 0.3%
Asian	35 20.3%	25 14.6%	60 17.5%
Black or African American	1 0.6%	2 1.2%	3 0.9%
White	129 75%	138 80.7%	267 77.8%
Other/Mixed	6 3.5%	6 3.5%	12 3.5%

Outcome Measures

1. Primary Outcome

Title	Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period
Description	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with available data were included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	168	170
Median (Full Range) [Seizures per 28 days]	-1.55	-3.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Lacosamide (FAS)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	=0.0003
	Comments
	Method	ANCOVA
	Comments	Seizure frequency (log transformed) is analyzed using analysis of covariance with terms for treatment, pooled center and Baseline seizure frequency.
Method of Estimation	Estimation Parameter	Percent reduction over Placebo
	Estimated Value	31.72
	Confidence Interval	(2-Sided) 95%; 16.342 to 44.277
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percent reduction over placebo is estimated as 100 x (1-exp[LSMLacosamide-LSMPlacebo]). Where LSM is Least Square Mean.

2. Secondary Outcome

Title	Proportion of Responders Where a Responder is Defined as a Participant With >= 50% Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Maintenance Period
Description	Proportion of responders is presented as percentage of participants. A responder is a subject experiencing a 50 % or greater reduction in partial onset seizure frequency per 28 days from Baseline to the Maintenance Period.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with response data have been included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	168	170
Number [percentage of participants]	33.3 19.4%	52.9 30.9%

3. Secondary Outcome

Title	Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the End of Maintenance Period
Description	Proportion of subjects is presented as percentage of participants. A >=25%-<50% response in the Maintenance Period is defined as >=25% to <50% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A >=50%-<=75% response in the Maintenance Period is defined as >=50% to <=75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period. A 75% response in the Maintenance Period is defined as >75% reduction in POS frequency per 28 days from Baseline to end of Maintenance Period.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	170	170
>=25% - <50%	14.7 8.5%	11.8 6.9%
>=50% - <=75%	17.1 9.9%	21.8 12.7%
>75%	15.9 9.2%	31.2 18.2%

4. Secondary Outcome

Title	Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
Description	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with available data were included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	169	170
Median (Full Range) [Seizures per 28 days]	-1.22	-2.46

5. Secondary Outcome

Title	Proportion of Subjects Experiencing a >=25 % to <50 %, 50 % to 75 %, or >75 % Reduction in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
Description	Proportion of subjects is presented as percentage of participants. A >=25%-<50% response in the Treatment Period is defined as >=25% to <50% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A >=50%-<=75% response in the Treatment Period is defined as >=50% to <=75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period. A 75% response in the Treatment Period is defined as >75% reduction in POS frequency per 28 days from Baseline to end of Treatment Period.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	170	170
>=25% - <50%	15.3 8.9%	16.5 9.6%
>=50% - <=75%	20.6 12%	20.6 12%
>75%	8.8 5.1%	23.5 13.7%

6. Secondary Outcome

Title	Proportion of Subjects Experiencing no Change in Partial Onset Seizure Frequency (Between <25 % Reduction and <25 % Increase) Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
Description	Proportion of subjects is presented as percentage of participants. No change is defined as between <25% reduction and <25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise not between <25% reduction and <25% increase is defined as a change.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with response data have been included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	169	170
Number [percentage of participants]	32.0 18.6%	20.6 12%

7. Secondary Outcome

Title	Proportion of Subjects Experiencing an Increase in Partial Onset Seizure Frequency Per 28 Days of >=25 % From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)
Description	Proportion of subjects is presented as percentage of participants. An increase is defined as a >=25% increase in POS frequency per 28 days from Baseline to the entire Treatment Period, otherwise <25% increase is defined as no increase.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with response data have been included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	169	170
Number [percentage of participants]	23.1 13.4%	18.8 11%

8. Secondary Outcome

Title	Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures
Description	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with Simple Partial Seizures were included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	68	77
Median (Full Range) [Seizures per 28 days]	-1.14	-1.25

9. Secondary Outcome

Title	Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures
Description	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with Complex Partial Seizures were included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	99	109
Median (Full Range) [Seizures per 28 days]	-0.98	-2.06

10. Secondary Outcome

Title	Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures
Description	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.
Time Frame	Baseline to Week 16 (or last value on treatment)

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects with Secondary Generalized Seizures were included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	69	63
Median (Full Range) [Seizures per 28 days]	-1.0	-2.81

11. Secondary Outcome

Title	Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period
Description	The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded.
Time Frame	Week 7 to Week 16

Outcome Measure Data

Analysis Population Description

Percentages are based on the number of subjects in the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects who completed the Maintenance Period have been included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	154	152
Mean (Standard Deviation) [days]	0.65 (0.35)	0.71 (0.32)

12. Secondary Outcome

Title	Proportion of Subjects Who Achieved "Seizure Free" Status (Yes/no) for Subjects Who Completed the Maintenance Period
Description	The proportion of seizure free days is calculated as (days with number of seizures = 0) divided by (days with recorded data in the subject diary), where 'days with recorded data in the subject diary' excludes any days where 'Not Done' is recorded.
Time Frame	Week 7 to Week 16

Outcome Measure Data

Analysis Population Description

Percentages are based on the number of subjects in the Full Analysis Set (FAS), which included all subjects who were randomized, received at least 1 dose of study medication, and had a Baseline and at least 1 post-Baseline assessment of seizure frequency data. Only subjects who completed the Maintenance Period have been included in this analysis.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.	This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
Measure Participants	154	152
Number [percentage of participants]	9.7 5.6%	15.1 8.8%

Adverse Events

Time Frame	Adverse events were collected from Visit 1 until Safety Follow-Up Visit up to week 24.
Arm/Group Title	Placebo		Lacosamide
Arm/Group Description	This arm includes subjects with epilepsy, who received a flexible dose of Placebo oral solution or tablets, administered twice a day. Appearance of Placebo oral solution and tablets matched the Lacosamide oral solution and tablets.		This arm includes subjects with epilepsy, who received a flexible dose of Lacosamide (LCM) oral solution or tablets, administered twice a day. Subjects weighing <30kg received 8mg/kg/day to 12mg/kg/day Lacosamide (LCM) oral solution; subjects weighing >=30kg to <50kg received 6mg/kg/day to 8mg/kg/day LCM oral solution; and subjects weighing >=50kg received 300mg/day to 400mg/day LCM tablets, or if unable or unwilling to swallow tablets may have received LCM oral solution, however, they were not permitted to exceed the maximum dose of LCM 400mg/day. The subject's body weight at Baseline (Visit 2) was used to determine the dose throughout the study.
All Cause Mortality
	Placebo		Lacosamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/172 (0%)		0/171 (0%)
Serious Adverse Events
	Placebo		Lacosamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/172 (7.6%)		11/171 (6.4%)
Cardiac disorders
Bradycardia	0/172 (0%)	0	1/171 (0.6%)	1
Gastrointestinal disorders
Abdominal pain	2/172 (1.2%)	2	0/171 (0%)	0
Vomiting	1/172 (0.6%)	2	1/171 (0.6%)	1
Constipation	1/172 (0.6%)	1	0/171 (0%)	0
Gastrointestinal inflammation	0/172 (0%)	0	1/171 (0.6%)	1
Hepatobiliary disorders
Hepatitis	1/172 (0.6%)	1	0/171 (0%)	0
Infections and infestations
Pneumonia	2/172 (1.2%)	2	0/171 (0%)	0
Urinary tract infection	1/172 (0.6%)	1	1/171 (0.6%)	1
Bronchitis	0/172 (0%)	0	1/171 (0.6%)	1
Bronchopneumonia	0/172 (0%)	0	1/171 (0.6%)	1
Dengue fever	0/172 (0%)	0	1/171 (0.6%)	1
Gastroenteritis	1/172 (0.6%)	1	0/171 (0%)	0
Respiratory tract infection	1/172 (0.6%)	1	0/171 (0%)	0
Tonsillitis	1/172 (0.6%)	1	0/171 (0%)	0
Injury, poisoning and procedural complications
Postoperative respiratory distress	1/172 (0.6%)	1	0/171 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/172 (0.6%)	1	1/171 (0.6%)	2
Musculoskeletal and connective tissue disorders
Back pain	1/172 (0.6%)	1	0/171 (0%)	0
Nervous system disorders
Convulsion	4/172 (2.3%)	5	2/171 (1.2%)	2
Dystonia	1/172 (0.6%)	1	0/171 (0%)	0
Partial seizures	0/172 (0%)	0	1/171 (0.6%)	4
Syncope	0/172 (0%)	0	1/171 (0.6%)	2
Psychiatric disorders
Emotional disorder of childhood	1/172 (0.6%)	1	0/171 (0%)	0
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/172 (0.6%)	1	0/171 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Lacosamide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/172 (35.5%)		85/171 (49.7%)
Gastrointestinal disorders
Vomiting	11/172 (6.4%)	15	17/171 (9.9%)	22
Diarrhoea	9/172 (5.2%)	13	8/171 (4.7%)	15
General disorders
Pyrexia	10/172 (5.8%)	11	17/171 (9.9%)	21
Infections and infestations
Nasopharyngitis	10/172 (5.8%)	10	20/171 (11.7%)	29
Upper respiratory tract infection	10/172 (5.8%)	14	10/171 (5.8%)	13
Pharyngitis	5/172 (2.9%)	5	10/171 (5.8%)	13
Nervous system disorders
Somnolence	11/172 (6.4%)	14	28/171 (16.4%)	42
Dizziness	13/172 (7.6%)	14	18/171 (10.5%)	26
Headache	15/172 (8.7%)	25	14/171 (8.2%)	19

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.