A Clinical Study to Investigate the Efficacy and Safety of Lacosamide as an Add on Therapy in Children With Epilepsy With Partial-onset Seizures

• ClinicalTrials.gov Identifier: NCT01964560
• Recruitment Status: Completed
• First Posted: October 17, 2013
• Results First Posted: October 25, 2022
• Last Update Posted: October 25, 2022
• Sponsor: UCB BIOSCIENCES, Inc.
• Collaborator: UCB Biopharma SRL
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES, Inc. )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Epilepsy
• Intervention: Drug: Lacosamide
• Enrollment: 540

Participant Flow

Recruitment Details	The study started to enroll participants in August 2014 and concluded in April 2022.
Pre-assignment Details	The Participant Flow refers to the Safety Set (SS). The SS included all enrolled study participants who took at least 1 dose of lacosamide (LCM) in this long-term extension study.

Arm/Group Title	Lacosamide (All Subjects)
Arm/Group Description	Participants who participated in primary study [SP0967 (NCT02477839) or SP0969 (NCT01921205)] consented and met requirements to participate in current study received LCM 10 milligram/kilogram/day (mg/kg/day) as an oral solution for study participants weighing <30 kg, LCM 6 mg/kg/day as an oral solution for study participants weighing >=30 kg to <50 kg, and LCM 300 mg/day as tablets for study participants weighing >=50 kg. LCM was administered twice daily (bid) up to Week 96. After 1 week the investigator might adjust the LCM dose during the Treatment based on clinical judgment within a range of 2 mg/kg/day to 12 mg/kg/day for the oral solution and 100 mg/day to 600 mg/day for the tablets.
Period Title: Overall Study
Started	540
Completed	395
Not Completed	145
Reason Not Completed
Adverse Event	23
Lack of Efficacy	46
Protocol deviation	2
Lost to Follow-up	4
Withdrawal by Subject	64
Surgery-hemispherotomy	1
Surgery	1
Seizures appeared resolved with epilepsy surgery	1
Patient and Investigator choice	1
Patient was prescribed CBD	1
Participant moved to another country	1

Baseline Characteristics

Arm/Group Title		Lacosamide (All Subjects)
Arm/Group Description		Participants who participated in primary study [SP0967 (NCT02477839) or SP0969 (NCT01921205)] consented and met requirements to participate in current study received LCM 10 milligram/kilogram/day (mg/kg/day) as an oral solution for study participants weighing <30 kg, LCM 6 mg/kg/day as an oral solution for study participants weighing >=30 kg to <50 kg, and LCM 300 mg/day as tablets for study participants weighing >=50 kg. LCM was administered twice daily (bid) up to Week 96. After 1 week the investigator might adjust the LCM dose during the Treatment based on clinical judgment within a range of 2 mg/kg/day to 12 mg/kg/day for the oral solution and 100 mg/day to 600 mg/day for the tablets.
Overall Number of Baseline Participants		540
Baseline Analysis Population Description		Baseline Characteristics refer to the Safety Set which consisted of all enrolled study participants who took at least 1 dose of LCM in this long-term extension study.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	540 participants
		7.486 (5.415)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	540 participants
	>=28 days - <24 months	103 19.1%
	>=24 months - <12 years	287 53.1%
	>=12 - <18 years	150 27.8%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	540 participants
	Female	236 43.7%
	Male	304 56.3%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	540 participants
American Indian/Alaskan native		18 3.3%
Asian		83 15.4%
Black		4 0.7%
White		414 76.7%
Other/mixed		21 3.9%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	540 participants
Hispanic or Latino		68 12.6%
Not Hispanic or Latino		472 87.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Description	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Treatment-emergent is defined as starting on or after the date of first dose of LCM in EP0034, and within 30 days of last dose.
Time Frame	From Week 0 to the End of Safety Follow-Up (up to Week 104)

Outcome Measure Data

Analysis Population Description

The Safety Set (SS) included all enrolled study participants who took at least 1 dose of LCM in this long-term extension study.

Arm/Group Title	Lacosamide (All Subjects)
Arm/Group Description:	Participants who participated in primary study [SP0967 (NCT02477839) or SP0969 (NCT01921205)] consented and met requirements to participate in current study received LCM 10 milligram/kilogram/day (mg/kg/day) as an oral solution for study participants weighing <30 kg, LCM 6 mg/kg/day as an oral solution for study participants weighing >=30 kg to <50 kg, and LCM 300 mg/day as tablets for study participants weighing >=50 kg. LCM was administered twice daily (bid) up to Week 96. After 1 week the investigator might adjust the LCM dose during the Treatment based on clinical judgment within a range of 2 mg/kg/day to 12 mg/kg/day for the oral solution and 100 mg/day to 600 mg/day for the tablets.
Overall Number of Participants Analyzed	540
Measure Type: Number; Unit of Measure: percentage of participants
	77.2

2. Primary Outcome

Title	Percentage of Participants With Serious TEAEs
Description	A serious adverse event (SAE) must meet 1 or more of the following criteria: • Death, • Life-threatening (Life-threatening does not include a reaction that might have caused death had it occurred in a more severe form.), • Significant or persistent disability/incapacity, • Congenital anomaly/birth defect (including that occurring in a fetus), • Important medical event that, based upon appropriate medical judgment, may jeopardize the patient or participant and may require medical or surgical intervention to prevent 1 of the other outcomes listed in the definition of serious., • Initial inpatient hospitalization or prolongation of hospitalization. Treatment-emergent is defined as starting on or after the date of first dose of LCM in EP0034, and within 30 days of last dose.
Time Frame	From Week 0 to the End of Safety Follow-Up (up to Week 104)

Outcome Measure Data

Analysis Population Description

The SS included all enrolled study participants who took at least 1 dose of LCM in this long-term extension study.

Arm/Group Title	Lacosamide (All Subjects)
Arm/Group Description:	Participants who participated in primary study [SP0967 (NCT02477839) or SP0969 (NCT01921205)] consented and met requirements to participate in current study received LCM 10 milligram/kilogram/day (mg/kg/day) as an oral solution for study participants weighing <30 kg, LCM 6 mg/kg/day as an oral solution for study participants weighing >=30 kg to <50 kg, and LCM 300 mg/day as tablets for study participants weighing >=50 kg. LCM was administered twice daily (bid) up to Week 96. After 1 week the investigator might adjust the LCM dose during the Treatment based on clinical judgment within a range of 2 mg/kg/day to 12 mg/kg/day for the oral solution and 100 mg/day to 600 mg/day for the tablets.
Overall Number of Participants Analyzed	540
Measure Type: Number; Unit of Measure: percentage of participants
	20.6

3. Primary Outcome

Title	Percentage of Participants With TEAEs Leading to Study Discontinuation
Description	An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs leading to study discontinuation. Treatment-emergent is defined as starting on or after the date of first dose of LCM in EP0034, and within 30 days of last dose.
Time Frame	From Week 0 to the End of Safety Follow-Up (up to Week 104)

Outcome Measure Data

Analysis Population Description

The SS included all enrolled study participants who took at least 1 dose of LCM in this long-term extension study. Here, only those participants who discontinued the study due to TEAEs starting on or after the date of first dose of LCM in EP0034, and within 30 days of last dose of LCM are reported.

Arm/Group Title	Lacosamide (All Subjects)
Arm/Group Description:	Participants who participated in primary study [SP0967 (NCT02477839) or SP0969 (NCT01921205)] consented and met requirements to participate in current study received LCM 10 milligram/kilogram/day (mg/kg/day) as an oral solution for study participants weighing <30 kg, LCM 6 mg/kg/day as an oral solution for study participants weighing >=30 kg to <50 kg, and LCM 300 mg/day as tablets for study participants weighing >=50 kg. LCM was administered twice daily (bid) up to Week 96. After 1 week the investigator might adjust the LCM dose during the Treatment based on clinical judgment within a range of 2 mg/kg/day to 12 mg/kg/day for the oral solution and 100 mg/day to 600 mg/day for the tablets.
Overall Number of Participants Analyzed	540
Measure Type: Number; Unit of Measure: percentage of participants
	4.1

4. Secondary Outcome

Title	Percentage of Seizure-free Days During the Study
Description	The number of seizure-free days was the total number of days within an interval for which daily diary data were available and no seizures were reported. The percentage of seizure-free days was computed as 100 times the number of seizure-free days in the interval divided by the number of days in the interval for which daily diary data were available. Percentage of seizure-free days was measured using data obtained from participant diaries from EP0034 and is presented for the overall Treatment only.
Time Frame	From Week 0 to End of Treatment (up to Week 96)

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) was used for the analysis of seizure data and included all study participants in the SS who had at least 1 completed post-Baseline seizure diary. Study participants whose efficacy data could not be source verified were excluded from the FAS. Here, Number of participants analyzed included those participants who were evaluable for the assessment.

Arm/Group Title	Lacosamide (All Subjects)
Arm/Group Description:	Participants who participated in primary study [SP0967 (NCT02477839) or SP0969 (NCT01921205)] consented and met requirements to participate in current study received LCM 10 milligram/kilogram/day (mg/kg/day) as an oral solution for study participants weighing <30 kg, LCM 6 mg/kg/day as an oral solution for study participants weighing >=30 kg to <50 kg, and LCM 300 mg/day as tablets for study participants weighing >=50 kg. LCM was administered twice daily (bid) up to Week 96. After 1 week the investigator might adjust the LCM dose during the Treatment based on clinical judgment within a range of 2 mg/kg/day to 12 mg/kg/day for the oral solution and 100 mg/day to 600 mg/day for the tablets.
Overall Number of Participants Analyzed	537
Mean (Standard Deviation); Unit of Measure: percentage of seizure free days
	66.96 (36.18)

Adverse Events

Time Frame	From Week 0 to the End of Safety Follow-Up (up to Week 104)
Adverse Event Reporting Description	TEAEs were events which started on or after date of first EP0034 dose of LCM, or whose intensity worsened on or after date of first EP0034 dose of LCM. AEs occurring within 30 days after last dose of LCM were considered treatment-emergent. SS included all enrolled study participants who took at least 1 dose of LCM in the long-term extension study.
Arm/Group Title	Lacosamide (All Subjects)
Arm/Group Description	Participants who participated in primary study [SP0967 (NCT02477839) or SP0969 (NCT01921205)] consented and met requirements to participate in current study received LCM 10 milligram/kilogram/day (mg/kg/day) as an oral solution for study participants weighing <30 kg, LCM 6 mg/kg/day as an oral solution for study participants weighing >=30 kg to <50 kg, and LCM 300 mg/day as tablets for study participants weighing >=50 kg. LCM was administered twice daily (bid) up to Week 96. After 1 week the investigator might adjust the LCM dose during the Treatment based on clinical judgment within a range of 2 mg/kg/day to 12 mg/kg/day for the oral solution and 100 mg/day to 600 mg/day for the tablets.
All-Cause Mortality
	Lacosamide (All Subjects)
	Affected / at Risk (%)
Total	7/540 (1.30%)
Serious Adverse Events
	Lacosamide (All Subjects)
	Affected / at Risk (%)	# Events
Total	111/540 (20.56%)
Blood and lymphatic system disorders
Idiopathic thrombocytopenic purpura * 1	1/540 (0.19%)	1
Lymphadenopathy * 1	1/540 (0.19%)	1
Cardiac disorders
Cardiac arrest * 1	1/540 (0.19%)	1
Congenital, familial and genetic disorders
Cerebral palsy * 1	1/540 (0.19%)	1
Talipes * 1	1/540 (0.19%)	2
Eye disorders
Blepharitis * 1	1/540 (0.19%)	1
Diplopia * 1	1/540 (0.19%)	1
Parophthalmia * 1	1/540 (0.19%)	1
Gastrointestinal disorders
Vomiting * 1	10/540 (1.85%)	12
Nausea * 1	4/540 (0.74%)	4
Abdominal pain * 1	2/540 (0.37%)	2
Constipation * 1	2/540 (0.37%)	2
Diarrhoea * 1	2/540 (0.37%)	2
Dyspepsia * 1	1/540 (0.19%)	1
Dysphagia * 1	1/540 (0.19%)	1
Enterocolitis * 1	1/540 (0.19%)	1
Gastrointestinal motility disorder * 1	1/540 (0.19%)	1
Gingival bleeding * 1	1/540 (0.19%)	1
Intestinal obstruction * 1	1/540 (0.19%)	1
Stomatitis * 1	1/540 (0.19%)	1
Upper gastrointestinal haemorrhage * 1	1/540 (0.19%)	1
General disorders
Pyrexia * 1	4/540 (0.74%)	4
Device malfunction * 1	2/540 (0.37%)	3
Cyst * 1	1/540 (0.19%)	1
Death * 1	1/540 (0.19%)	1
Device breakage * 1	1/540 (0.19%)	1
Device occlusion * 1	1/540 (0.19%)	1
Infections and infestations
Pneumonia * 1	11/540 (2.04%)	14
Bronchitis * 1	5/540 (0.93%)	5
Upper respiratory tract infection * 1	4/540 (0.74%)	5
Bronchopneumonia * 1	3/540 (0.56%)	4
Dengue fever * 1	2/540 (0.37%)	2
Gastroenteritis * 1	2/540 (0.37%)	3
Gastroenteritis viral * 1	2/540 (0.37%)	2
Influenza * 1	2/540 (0.37%)	2
Rhinovirus infection * 1	2/540 (0.37%)	2
Abscess neck * 1	1/540 (0.19%)	1
Acute tonsillitis * 1	1/540 (0.19%)	1
Adenovirus infection * 1	1/540 (0.19%)	1
Amoebic dysentery * 1	1/540 (0.19%)	1
Bronchiolitis * 1	1/540 (0.19%)	1
Corona virus infection * 1	1/540 (0.19%)	1
Device related sepsis * 1	1/540 (0.19%)	1
Diarrhoea infectious * 1	1/540 (0.19%)	1
Ear infection * 1	1/540 (0.19%)	1
Enterovirus infection * 1	1/540 (0.19%)	1
Gastroenteritis rotavirus * 1	1/540 (0.19%)	1
Gastrointestinal infection * 1	1/540 (0.19%)	1
Helicobacter infection * 1	1/540 (0.19%)	1
Nasopharyngitis * 1	1/540 (0.19%)	1
Oral herpes * 1	1/540 (0.19%)	1
Otitis media * 1	1/540 (0.19%)	1
Otitis media acute * 1	1/540 (0.19%)	1
Periorbital cellulitis * 1	1/540 (0.19%)	1
Pharyngotonsillitis * 1	1/540 (0.19%)	1
Pneumonia influenzal * 1	1/540 (0.19%)	1
Pneumonia pneumococcal * 1	1/540 (0.19%)	1
Pneumonia respiratory syncytial viral * 1	1/540 (0.19%)	1
Pneumonia viral * 1	1/540 (0.19%)	1
Pyelonephritis acute * 1	1/540 (0.19%)	1
Respiratory syncytial virus infection * 1	1/540 (0.19%)	1
Sepsis * 1	1/540 (0.19%)	1
Urinary tract infection * 1	1/540 (0.19%)	2
Viral infection * 1	1/540 (0.19%)	1
Injury, poisoning and procedural complications
Contusion * 1	2/540 (0.37%)	2
Clavicle fracture * 1	1/540 (0.19%)	1
Head injury * 1	1/540 (0.19%)	1
Joint dislocation * 1	1/540 (0.19%)	1
Lip injury * 1	1/540 (0.19%)	1
Post procedural fistula * 1	1/540 (0.19%)	1
Tooth fracture * 1	1/540 (0.19%)	1
Toxicity to various agents * 1	1/540 (0.19%)	1
Upper limb fracture * 1	1/540 (0.19%)	1
Investigations
Blood bicarbonate decreased * 1	1/540 (0.19%)	1
Liver function test abnormal * 1	1/540 (0.19%)	1
Urine output decreased * 1	1/540 (0.19%)	1
Metabolism and nutrition disorders
Dehydration * 1	2/540 (0.37%)	2
Acetonaemia * 1	1/540 (0.19%)	1
Decreased appetite * 1	1/540 (0.19%)	1
Enteral feeding intolerance * 1	1/540 (0.19%)	1
Hypoglycaemia * 1	1/540 (0.19%)	1
Hypophagia * 1	1/540 (0.19%)	2
Metabolic acidosis * 1	1/540 (0.19%)	1
Musculoskeletal and connective tissue disorders
Muscle haemorrhage * 1	1/540 (0.19%)	1
Nervous system disorders
Convulsion * 1	24/540 (4.44%)	30
Status epilepticus * 1	9/540 (1.67%)	11
Epilepsy * 1	7/540 (1.30%)	10
Partial seizures * 1	4/540 (0.74%)	4
Dizziness * 1	3/540 (0.56%)	3
Partial seizures with secondary generalisation * 1	3/540 (0.56%)	5
Febrile convulsion * 1	2/540 (0.37%)	2
Hemiparesis * 1	2/540 (0.37%)	2
Somnolence * 1	2/540 (0.37%)	3
Altered state of consciousness * 1	1/540 (0.19%)	2
Cognitive disorder * 1	1/540 (0.19%)	1
Grand mal convulsion * 1	1/540 (0.19%)	1
Headache * 1	1/540 (0.19%)	1
Hypotonia * 1	1/540 (0.19%)	1
Intracranial haematoma * 1	1/540 (0.19%)	1
Motor dysfunction * 1	1/540 (0.19%)	1
Myoclonic epilepsy * 1	1/540 (0.19%)	1
Subdural hygroma * 1	1/540 (0.19%)	1
Tonic convulsion * 1	1/540 (0.19%)	1
Psychiatric disorders
Disorientation * 1	1/540 (0.19%)	1
Emotional disorder of childhood * 1	1/540 (0.19%)	1
Suicide attempt * 1	1/540 (0.19%)	2
Renal and urinary disorders
Pyuria * 1	1/540 (0.19%)	1
Renal failure acute * 1	1/540 (0.19%)	1
Vesicoureteric reflux * 1	1/540 (0.19%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory distress * 1	3/540 (0.56%)	3
Respiratory failure * 1	3/540 (0.56%)	3
Pneumonia aspiration * 1	2/540 (0.37%)	2
Apnoea * 1	1/540 (0.19%)	1
Bronchospasm * 1	1/540 (0.19%)	1
Chylothorax * 1	1/540 (0.19%)	1
Dyspnoea * 1	1/540 (0.19%)	3
Epistaxis * 1	1/540 (0.19%)	1
Hypoventilation * 1	1/540 (0.19%)	1
Hypoxia * 1	1/540 (0.19%)	1
Interstitial lung disease * 1	1/540 (0.19%)	1
Tonsillar hypertrophy * 1	1/540 (0.19%)	1
Skin and subcutaneous tissue disorders
Dermatitis * 1	1/540 (0.19%)	1
Drug reaction with eosinophilia and systemic symptoms * 1	1/540 (0.19%)	1
Surgical and medical procedures
Brain operation * 1	1/540 (0.19%)	1
Vascular disorders
Deep vein thrombosis * 1	1/540 (0.19%)	1
Hypotension * 1	1/540 (0.19%)	1
1 Term from vocabulary, MedDRA v16.1; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Lacosamide (All Subjects)
	Affected / at Risk (%)	# Events
Total	289/540 (53.52%)
Gastrointestinal disorders
Vomiting * 1	56/540 (10.37%)	113
Diarrhoea * 1	42/540 (7.78%)	54
General disorders
Pyrexia * 1	86/540 (15.93%)	149
Infections and infestations
Upper respiratory tract infection * 1	83/540 (15.37%)	167
Nasopharyngitis * 1	57/540 (10.56%)	92
Pharyngitis * 1	39/540 (7.22%)	68
Bronchitis * 1	33/540 (6.11%)	46
Influenza * 1	28/540 (5.19%)	35
Nervous system disorders
Somnolence * 1	30/540 (5.56%)	42
Headache * 1	29/540 (5.37%)	89
Convulsion * 1	27/540 (5.00%)	33
Respiratory, thoracic and mediastinal disorders
Cough * 1	38/540 (7.04%)	49
1 Term from vocabulary, MedDRA v16.1; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Results Point of Contact

• Name/Title: UCB
• Organization: Cares
• Phone: 001 844 599 2273
• EMail: UCBCares@ucb.com

• Responsible Party: UCB Pharma ( UCB BIOSCIENCES, Inc. )
• ClinicalTrials.gov Identifier: NCT01964560
• Other Study ID Numbers: EP0034; 2012-005012-26 ( EudraCT Number )
• First Submitted: October 14, 2013
• First Posted: October 17, 2013
• Results First Submitted: September 30, 2022
• Results First Posted: October 25, 2022
• Last Update Posted: October 25, 2022