Efficacy and Safety of Lacosamide as Adjunctive Therapy in Subjects ≥1 Month to <4 Years With Partial-onset Seizures

• Sponsor: UCB BIOSCIENCES, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02477839
• Collaborator: (none)
• Enrollment: 255
• Locations: 88
• Arms: 2
• Actual Duration (Months): 59.8
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this trial is to assess the efficacy, safety and tolerability of lacosamide administered as add-on therapy with 1 to 3 anti-seizure medications. This trial is for children aged 1 month to less than 4 years with epilepsy who currently have uncontrolled partial-onset seizures.

Condition or Disease	Intervention/Treatment	Phase
Epilepsy With Partial-onset Seizures	Drug: Lacosamide; Other: Placebo	Phase 3

Detailed Description

The trial consists of a 7-day Baseline Period, a 20-day Titration Period, a 7-day Maintenance Period, and a 12-day Transition Period for subjects who complete the study and choose to enter the extension study. Subjects who will not enter the extension study will continue after the Maintenance Period with a 16-day Taper Period followed by a 30-day Safety Follow-Up Period. The Taper Period and Safety Follow-Up are also applicable for subjects not eligible for continuation and therefore ending the study earlier.

If subjects meet the eligibility criteria, they will be randomized to receive either lacosamide 8 mg/kg/day to 12 mg/kg/day, or placebo during the Maintenance Phase. The dose of lacosamide will be titrated from 4 mg/kg/day at study start to maximum of 12 mg/kg/day at 4-day intervals of 1-2 mg/kg/day.

All subjects who complete the 20-day Titration Period will enter the 7-day Maintenance Period. No dose adjustment is allowed during the Maintenance Phase. The Treatment Phase is defined as the combined Titration and Maintenance Phases.

Study Design

• Study Type: Interventional
• Actual Enrollment: 255 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 >=1 Month to <4 Years of Age With Partial-Onset Seizures
• Actual Study Start Date: Jun 5, 2015
• Actual Primary Completion Date: May 28, 2020
• Actual Study Completion Date: May 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Lacosamide Lacosamide syrup 8 mg/kg/day to 12 mg/kg/day	Drug: Lacosamide; Active Substance: Lacosamide Pharmaceutical Form: Syrup Concentration: 10 mg/mL Route of Administration: oral; Other Names: Vimpat UCB Code: SPM 927 Abbreviated name: LCM
Placebo Comparator: Placebo Matching placebo syrup	Other: Placebo; Active Substance: Placebo Pharmaceutical Form: Syrup Concentration: N/A Route of Administration: oral; Other Names: PBO

Outcome Measures

Primary Outcome Measures

1. Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG [End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)]

   The change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-electroencephalogram (EEG) compared to the End-of-Baseline Period video-EEG. Seizure frequency was analyzed using an analysis of covariance (ANCOVA) with terms for treatment, pooled randomized age stratum, pooled center, and Baseline seizure ADF. Seizure ADF was log transformed using the transformation of ln(X+1), where X is the seizure ADF. Baseline seizure ADF was log transformed. Least squares means were based on log-transformed data of the full ANCOVA model.

2. Participant Withdrawals Due to Adverse Events (AEs) During the Study [From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)]

   An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.

3. Percentage of Participants With Adverse Events Reported Spontaneously by the Participant's Parent(s) and/or Legal Representative(s)/Caregiver(s) (in Accordance With Local Regulation) or Observed by the Investigator [From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)]

   An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.

Secondary Outcome Measures

1. Absolute Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG [End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)]

   The absolute change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG.

2. Percent Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG [End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)]

   The percent change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG.

3. Percentage of Participants Who Achieved 'Seizure-free' Status From All Seizure Types During the End-of-Maintenance (EOM) Period Video-EEG [During the End-of-Maintenance Period (Day 24 to Day 27)]

   A study participant was considered seizure-free from all seizures if the End-of-Maintenance (EOM) Period video-EEG had zero seizures reported from all seizure types (not just partial-onset seizures (POS)).

4. Percentage of Participants Who Achieved 'Seizure-free' Status From Partial-onset Seizure Types Only During the End-of-Maintenance (EOM) Period Video-EEG [During the End-of-Maintenance Period (Day 24 to Day 27)]

   A study participant was considered seizure free from partial-onset seizures (POS) if the End-of-Maintenance (EOM) Period video-EEG had zero POS reported.

5. Percentage of Participants Experiencing a >=25% to <50% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG [End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)]

   A ≥25% to <50% response was defined as ≥25% to <50% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.

6. Percentage of Participants Experiencing a 50% to 75% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG [End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)]

   A ≥50% to ≤75% response was defined as ≥50% to ≤75% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.

7. Percentage of Participants Experiencing a >75% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG [End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)]

   A >75% response was defined as >75% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.

8. Percentage of Participants Experiencing no Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures (Between <25% Reduction and <25% Increase) From EOB Period Video-EEG to EOM Period Video-EEG [End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)]

   No change was defined as between <25% reduction and <25% increase in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.

9. Percentage of Participants Experiencing an Increase in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures of >=25% From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG [End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)]

   An increase was defined as ≥25% increase in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Month to 47 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is male or female from >=1 month (ie, 4 weeks after full term [37 weeks gestational age]) to <4 years of age

• Subject has a diagnosis of epilepsy with partial-onset seizures. The results of >=1 prior EEG and >=1 magnetic resonance imaging/computerized tomography scan should be consistent with this diagnosis

• Subject weighs >=4 kg to <30 kg at Visit 1

• Subject has experienced >=2 partial-onset seizures with or without secondary generalization during each consecutive 7-day period during the 2 weeks prior to Visit 1

• Subject has >=2 partial-onset seizures with or without secondary generalization during the End-of-Baseline video-EEG. Electrographic seizures are defined as recognizable ictal patterns on an EEG involving >=2 contiguous electrodes. The seizures are initiated as a unilateral or strongly asymmetric abnormal epileptiform discharge lasting a total of >10 seconds

• Subject is on a stable (concurrently or sequentially) dosage regimen of 1 to 3 AEDs. The dosage regimen of concomitant AED therapy must be kept constant for a period of

=2 weeks prior to Visit 1. A stable daily dosage regimen of a concomitant benzodiazepine (BZD) will be considered as a concomitant AED

• Vagus nerve stimulation (VNS) is allowed and will not be counted as a concomitant AED. The VNS device must have been implanted for >=6 months prior to Visit 1; device settings must be kept stable for >=2 weeks prior to Visit 1 and kept stable during the Baseline, Treatment, and Transition Periods. Use of the VNS device magnet is allowed

• Subject is an acceptable candidate for venipuncture

Exclusion Criteria:

• Subject has experienced febrile seizures exclusively. The occurrence of febrile seizures in addition to partial-onset seizures is not exclusionary

• Subject is on a ketogenic diet that has either changed within the 4 weeks prior to Visit 1 or is expected to change during the study

• Subject has creatinine clearance <30 mL/minute

• 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] >=450 ms)

• Subject has a hemodynamically significant congenital heart disease

• Subject has an arrhythmic heart condition requiring medical therapy

• Subject has a known history of severe anaphylactic reaction secondary to medication intake or serious blood dyscrasias

• Subject has nonepileptic events that could be confused with seizures. Subjects may be included if epileptic events can be clearly distinguished and the frequency meets the study inclusion criteria

• Subject has a current diagnosis of Lennox-Gastaut syndrome, epilepsia partialis continua, primary generalized epilepsy, Dravet Syndrome, or seizures that are not of partial-onset origin

• Subject has a history of generalized convulsive status epilepticus <=2 months prior to Screening (Visit 1)

• 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. Subjects treated with felbamate for >=12 months prior to Visit 1 and who have not experienced serious toxicity issues are eligible

• Subject has an acute or subacutely 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)

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sp0967 638	Birmingham	Alabama	United States	35233
2	Sp0967 117	Tampa	Florida	United States	33609
3	Sp0967 115	Henderson	Nevada	United States	89052
4	Sp0967 120	Lebanon	New Hampshire	United States	03756
5	Sp0967 129	Dallas	Texas	United States	75235
6	Sp0967 630	San Antonio	Texas	United States	78207
7	Sp0967 643	San Antonio	Texas	United States	78249
8	Sp0967 142	Córdoba		Argentina
9	Sp0967 158	Passo Fundo		Brazil
10	Sp0967 152	Porto Alegre		Brazil
11	Sp0967 150	São Paulo		Brazil
12	Sp0967 154	São Paulo		Brazil
13	Sp0967 310	Plovdiv		Bulgaria
14	Sp0967 530	Beijing		China
15	Sp0967 535	Changchun		China
16	Sp0967 532	Chongqing		China
17	Sp0967 536	Nanchang		China
18	Sp0967 531	Shanghai		China
19	Sp0967 537	Shenzhen		China
20	Sp0967 613	Osijek		Croatia
21	Sp0967 610	Rijeka		Croatia
22	Sp0967 612	Zagreb		Croatia
23	Sp0967 320	Ostrava-Poruba		Czechia
24	Sp0967 349	Marseille		France
25	Sp0967 346	Rennes		France
26	Sp0967 344	Strasbourg		France
27	Sp0967 620	Tbilisi		Georgia
28	Sp0967 621	Tbilisi		Georgia
29	Sp0967 622	Tbilisi		Georgia
30	Sp0967 623	Tbilisi		Georgia
31	Sp0967 542	Athens		Greece
32	Sp0967 361	Budapest		Hungary
33	Sp0967 362	Budapest		Hungary
34	Sp0967 363	Budapest		Hungary
35	Sp0967 364	Budapest		Hungary
36	Sp0967 368	Budapest		Hungary
37	Sp0967 374	Petah tikva		Israel
38	Sp0967 397	Genova		Italy
39	Sp0967 398	Messina		Italy
40	Sp0967 381	Milano		Italy
41	Sp0967 700	Napoli		Italy
42	Sp0967 383	Roma		Italy
43	Sp0967 395	Roma		Italy
44	Sp0967 212	Seoul		Korea, Republic of
45	Sp0967 215	Seoul		Korea, Republic of
46	Sp0967 694	Aguascalientes		Mexico
47	Sp0967 561	Chihuahua		Mexico
48	Sp0967 569	Culiacán		Mexico
49	Sp0967 693	Culiacán		Mexico
50	Sp0967 563	Guadalajara		Mexico
51	Sp0967 564	Mexico		Mexico
52	Sp0967 568	Monterrey		Mexico
53	Sp0967 692	Monterrey		Mexico
54	Sp0967 650	Chisinau		Moldova, Republic of
55	Sp0967 720	Cebu		Philippines
56	Sp0967 724	Cebu		Philippines
57	Sp0967 721	Manila		Philippines
58	Sp0967 723	Manila		Philippines
59	Sp0967 727	Quezon City		Philippines
60	Sp0967 422	Kraków		Poland
61	Sp0967 750	Lisbon		Portugal
62	Sp0967 581	Bucuresti		Romania
63	Sp0967 582	Iaşi		Romania
64	Sp0967 573	Sibiu		Romania
65	Sp0967 577	Timişoara		Romania
66	Sp0967 454	Kemerovo		Russian Federation
67	Sp0967 456	Nizhny Novgorod		Russian Federation
68	Sp0967 452	Novosibirsk		Russian Federation
69	Sp0967 453	Omsk		Russian Federation
70	Sp0967 455	Perm		Russian Federation
71	Sp0967 730	Smolensk		Russian Federation
72	Sp0967 458	Tomsk		Russian Federation
73	Sp0967 459	Ulyanovsk		Russian Federation
74	Sp0967 450	Yekaterinburg		Russian Federation
75	Sp0967 461	Belgrade		Serbia
76	Sp0967 464	Belgrade		Serbia
77	Sp0967 463	Novi Sad		Serbia
78	Sp0967 474	Bratislava		Slovakia
79	Sp0967 224	Taipei		Taiwan
80	Sp0967 237	Bangkok		Thailand
81	Sp0967 235	Pathum Wan		Thailand
82	Sp0967 602	Dnipropetrovs'k		Ukraine
83	Sp0967 609	Dnipro		Ukraine
84	Sp0967 681	Ivano-Frankivs'k		Ukraine
85	Sp0967 600	Kiev		Ukraine
86	Sp0967 606	Kiev		Ukraine
87	Sp0967 682	Uzhgorod		Ukraine
88	Sp0967 603	Vinnytsia		Ukraine

Sponsors and Collaborators

• UCB BIOSCIENCES, Inc.

Investigators

• Study Director: UCB Cares, [phone] (UCB)

Study Documents (Full-Text)

• Study Protocol - Apr 5, 2018
• Statistical Analysis Plan - May 7, 2020

More Information

Publications

None provided.

• Responsible Party: UCB BIOSCIENCES, Inc.
• ClinicalTrials.gov Identifier: NCT02477839
• Other Study ID Numbers: SP0967; 2013-000717-20
• First Posted: Jun 23, 2015
• Last Update Posted: Jul 1, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by UCB BIOSCIENCES, Inc.: Epilepsy; children; partial-onset seizures; lacosamide; LCM; pediatric
• Additional relevant MeSH terms: Epilepsy; Seizures; Lacosamide

Study Results

Participant Flow

Recruitment Details	The study started to enroll patients in June 2015 and concluded in May 2020.
Pre-assignment Detail	Completed study was defined as participants who had "Completed study participant" selected as status at termination. The total number of participants who completed the study comprises of those who completed the Transition Period and the ones that completed the Taper Period after completing the Maintenance Period. Participant Flow refers to the SS.

Arm/Group Title	Placebo	Lacosamide
Arm/Group Description	Participants received matching placebo syrup.	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day.
Period Title: Overall Study
STARTED	127	128
Completed Transition Period	124	117
Completed Taper After Maintenance	0	1
COMPLETED	124	118
NOT COMPLETED	3	10

Baseline Characteristics

Arm/Group Title	Placebo	Lacosamide	Total Title
Arm/Group Description	Participants received matching placebo syrup.	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day.
Overall Participants	127	128	255
Age (Count of Participants)
<=18 years	127 100%	128 100%	255 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	26.1 (13.4)	25.2 (13.6)	25.6 (13.5)
Sex: Female, Male (Count of Participants)
Female	52 40.9%	57 44.5%	109 42.7%
Male	75 59.1%	71 55.5%	146 57.3%
Race/Ethnicity, Customized (Count of Participants)
American Indian/Alaskan Native	5 3.9%	13 10.2%	18 7.1%
Asian	15 11.8%	14 10.9%	29 11.4%
Black	0 0%	2 1.6%	2 0.8%
White	101 79.5%	94 73.4%	195 76.5%
Other/Mixed	6 4.7%	5 3.9%	11 4.3%

Outcome Measures

1. Primary Outcome

Title	Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
Description	The change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-electroencephalogram (EEG) compared to the End-of-Baseline Period video-EEG. Seizure frequency was analyzed using an analysis of covariance (ANCOVA) with terms for treatment, pooled randomized age stratum, pooled center, and Baseline seizure ADF. Seizure ADF was log transformed using the transformation of ln(X+1), where X is the seizure ADF. Baseline seizure ADF was log transformed. Least squares means were based on log-transformed data of the full ANCOVA model.
Time Frame	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). The analysis consisted of all study participants in the FAS who had at least 48 hours of interpretable recordings during the EOB Period video-EEG and the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	120	116
Least Squares Mean (Standard Error) [percent change]	1.44 (0.06)	1.40 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Lacosamide (FAS)
	Comments	Difference ratio in LS Mean was calculated as the exp [LSMLCM-LSMplacebo].
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo (FAS), Lacosamide (FAS)
	Comments	Percent reduction over placebo was estimated as 100 x (1-exp [LSMLCM-LSMPBO]).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	=0.6895
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Percent reduction
	Estimated Value	3.19
	Confidence Interval	(2-Sided) 95%; -13.59 to 17.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Participant Withdrawals Due to Adverse Events (AEs) During the Study
Description	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.
Time Frame	From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)

Outcome Measure Data

Analysis Population Description

The Safety Set (SS) included all randomized study participants who took at least 1 dose of study medication.

Arm/Group Title	Placebo (SS)	Lacosamide (SS)
Arm/Group Description	Participants received matching placebo syrup, forming the Safety Set (SS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the SS.
Measure Participants	127	128
Number [percentage of participants]	0 0%	1.6 1.3%

3. Primary Outcome

Title	Percentage of Participants With Adverse Events Reported Spontaneously by the Participant's Parent(s) and/or Legal Representative(s)/Caregiver(s) (in Accordance With Local Regulation) or Observed by the Investigator
Description	An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. An AE could, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study medication.
Time Frame	From the Baseline Period (Day -7) to the End of Study Visit (up to 93 days)

Outcome Measure Data

Analysis Population Description

The Safety Set (SS) included all randomized study participants who took at least 1 dose of study medication.

Arm/Group Title	Placebo (SS)	Lacosamide (SS)
Arm/Group Description	Participants received matching placebo syrup, forming the Safety Set (SS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the SS.
Measure Participants	127	128
Number [percentage of participants]	59.1 46.5%	56.3 44%

4. Secondary Outcome

Title	Absolute Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
Description	The absolute change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG.
Time Frame	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). The analysis consisted of all study participants in the FAS who had at least 48 hours of interpretable recordings during the EOB Period video-EEG and the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	123	121
Mean (Standard Deviation) [seizures per day]	-4.7650 (18.0115)	-2.9427 (7.4938)

5. Secondary Outcome

Title	Percent Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
Description	The percent change in ADF of electrographic partial-onset seizures as measured on the End-of-Maintenance Period video-EEG compared to the End-of-Baseline Period video-EEG.
Time Frame	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). The analysis consisted of all study participants in the FAS who had at least 48 hours of interpretable recordings during the EOB Period video-EEG and the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	122	121
Mean (Standard Deviation) [percent change]	-26.7927 (58.5564)	-32.3564 (65.0255)

6. Secondary Outcome

Title	Percentage of Participants Who Achieved 'Seizure-free' Status From All Seizure Types During the End-of-Maintenance (EOM) Period Video-EEG
Description	A study participant was considered seizure-free from all seizures if the End-of-Maintenance (EOM) Period video-EEG had zero seizures reported from all seizure types (not just partial-onset seizures (POS)).
Time Frame	During the End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). Percentages were based on the number of study participants in the FAS who completed at least 48 hours of interpretable video-EEG recordings during the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	120	117
Number [percentage of participants]	15.8 12.4%	17.1 13.4%

7. Secondary Outcome

Title	Percentage of Participants Who Achieved 'Seizure-free' Status From Partial-onset Seizure Types Only During the End-of-Maintenance (EOM) Period Video-EEG
Description	A study participant was considered seizure free from partial-onset seizures (POS) if the End-of-Maintenance (EOM) Period video-EEG had zero POS reported.
Time Frame	During the End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). Percentages were based on the number of study participants in the FAS who completed at least 48 hours of interpretable video-EEG recordings during the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	120	117
Number [percentage of participants]	16.7 13.1%	18.8 14.7%

8. Secondary Outcome

Title	Percentage of Participants Experiencing a >=25% to <50% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
Description	A ≥25% to <50% response was defined as ≥25% to <50% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.
Time Frame	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). Percentages were based on the number of study participants in the FAS who had at least 48 hours of interpretable recordings during the EOB Period video-EEG and the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	120	116
Number [percentage of participants]	18.3 14.4%	18.1 14.1%

9. Secondary Outcome

Title	Percentage of Participants Experiencing a 50% to 75% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
Description	A ≥50% to ≤75% response was defined as ≥50% to ≤75% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.
Time Frame	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). Percentages were based on the number of study participants in the FAS who had at least 48 hours of interpretable recordings during the EOB Period video-EEG and the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	120	116
Number [percentage of participants]	17.5 13.8%	10.3 8%

10. Secondary Outcome

Title	Percentage of Participants Experiencing a >75% Reduction in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
Description	A >75% response was defined as >75% reduction in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.
Time Frame	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). Percentages were based on the number of study participants in the FAS who had at least 48 hours of interpretable recordings during the EOB Period video-EEG and the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	120	116
Number [percentage of participants]	20.0 15.7%	31.0 24.2%

11. Secondary Outcome

Title	Percentage of Participants Experiencing no Change in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures (Between <25% Reduction and <25% Increase) From EOB Period Video-EEG to EOM Period Video-EEG
Description	No change was defined as between <25% reduction and <25% increase in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.
Time Frame	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). Percentages were based on the number of study participants in the FAS who had at least 48 hours of interpretable recordings during the EOB Period video-EEG and the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	120	116
Number [percentage of participants]	28.3 22.3%	27.6 21.6%

12. Secondary Outcome

Title	Percentage of Participants Experiencing an Increase in Average Daily Frequency (ADF) of Electrographic Partial-onset Seizures of >=25% From End-of-Baseline (EOB) Period Video-EEG to End-of-Maintenance (EOM) Period Video-EEG
Description	An increase was defined as ≥25% increase in ADF of electrographic partial-onset seizures (POS) from the End-of-Baseline (EOB) video-EEG to the End-of-Maintenance (EOM) video-EEG.
Time Frame	End-of-Baseline Period (Day -3 to Day 1) to End-of-Maintenance Period (Day 24 to Day 27)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) included all study participants in the Safety Set (SS). Percentages were based on the number of study participants in the FAS who had at least 48 hours of interpretable recordings during the EOB Period video-EEG and the EOM Period video-EEG.

Arm/Group Title	Placebo (FAS)	Lacosamide (FAS)
Arm/Group Description	Participants received matching placebo syrup, forming the Full Analysis Set (FAS).	Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the FAS.
Measure Participants	120	116
Number [percentage of participants]	15.0 11.8%	12.9 10.1%

Adverse Events

Time Frame	Treatment-emergent adverse events were collected from the Titration Period (Day 1) to the End of Study Visit (up to 86 days)
Adverse Event Reporting Description	Treatment-emergent AEs (TEAEs) were defined as those events that start on or after the date of first study medication administration and within 30 days following the date of final study medication administration, or whose severity worsens within this time frame.
Arm/Group Title	Placebo (SS)		Lacosamide (SS)
Arm/Group Description	Participants received matching placebo syrup, forming the Safety Set (SS).		Participants received lacosamide (LCM) syrup 8 mg/kg/day to 12 mg/kg/day, forming the SS.
All Cause Mortality
	Placebo (SS)		Lacosamide (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/127 (0%)		0/128 (0%)
Serious Adverse Events
	Placebo (SS)		Lacosamide (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/127 (4.7%)		6/128 (4.7%)
Gastrointestinal disorders
Vomiting	0/127 (0%)	0	2/128 (1.6%)	2
General disorders
Pyrexia	1/127 (0.8%)	1	0/128 (0%)	0
Infections and infestations
Oral herpes	1/127 (0.8%)	1	0/128 (0%)	0
Pneumonia	0/127 (0%)	0	1/128 (0.8%)	1
Upper respiratory tract infection	1/127 (0.8%)	1	0/128 (0%)	0
Urinary tract infection	1/127 (0.8%)	1	0/128 (0%)	0
Viral infection	0/127 (0%)	0	1/128 (0.8%)	1
Injury, poisoning and procedural complications
Thermal burn	1/127 (0.8%)	1	0/128 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/127 (0.8%)	1	0/128 (0%)	0
Nervous system disorders
Convulsion	0/127 (0%)	0	2/128 (1.6%)	3
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration	1/127 (0.8%)	1	0/128 (0%)	0
Respiratory failure	1/127 (0.8%)	1	0/128 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo (SS)		Lacosamide (SS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/127 (23.6%)		31/128 (24.2%)
General disorders
Pyrexia	15/127 (11.8%)	20	7/128 (5.5%)	9
Irritability	6/127 (4.7%)	6	7/128 (5.5%)	7
Infections and infestations
Upper respiratory tract infection	13/127 (10.2%)	14	6/128 (4.7%)	6
Nervous system disorders
Somnolence	5/127 (3.9%)	6	18/128 (14.1%)	22

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.