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

Epilepsy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01921205
• Other study ID #: SP0969
• Secondary ID: 2012-004996-38
• Status: Completed
• Phase: Phase 3
• Start date: August 29, 2013
• Est. completion date: January 24, 2017

Study information

• Verified date: March 2018
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 404
• Est. completion date: January 24, 2017
• Est. primary completion date: January 24, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years to 16 Years

Eligibility

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)

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

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:
• 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)

Locations

Country	Name	City	State
Argentina	143	Buenos Aires
Argentina	142	Cordoba
Australia	200	Heidelberg West
Australia	203	Herston
Australia	205	South Brisbane
Belgium	304	Brussels
Bulgaria	310	Sofia
Bulgaria	312	Sofia
Colombia	172	Floridablanca
Colombia	171	Medellin
Croatia	613	Osijek
Croatia	610	Rijeka
Croatia	612	Zagreb
Czechia	321	Hradec Kralove
Czechia	320	Ostrava-Poruba
Czechia	322	Praha 4
Czechia	323	Praha 5
Estonia	331	Tallinn
Estonia	330	Tartu
Georgia	620	Tbilisi
Georgia	621	Tbilisi
Georgia	622	Tbilisi
Georgia	623	Tbilisi
Hungary	361	Budapest
Hungary	362	Budapest
Hungary	363	Budapest
Hungary	364	Budapest
Hungary	360	Debrecen
Hungary	367	Miskolc
Hungary	366	Pecs
Israel	370	Holon
Israel	371	Kfar Saba
Israel	374	Petach Tikva
Israel	372	Tel Aviv
Italy	384	Bologna
Italy	388	Florence
Italy	387	Genova
Italy	380	Mantova
Italy	381	Milano
Italy	393	Padova
Italy	383	Roma
Italy	392	Roma
Italy	386	Verona
Korea, Republic of	211	Daegu
Korea, Republic of	210	Seoul
Korea, Republic of	212	Seoul
Korea, Republic of	213	Seoul
Korea, Republic of	215	Seoul
Latvia	400	Riga
Latvia	402	Valmiera
Lithuania	411	Kaunas
Mexico	569	Culiacan
Mexico	563	Guadalajara
Mexico	568	Monterrey
Montenegro	660	Podgorica
Poland	433	Gdansk
Poland	432	Katowice
Poland	420	Kielce
Poland	422	Krakow
Poland	431	Krakow
Poland	423	Poznan
Poland	425	Poznan
Poland	421	Szczecin
Poland	429	Tyniec Maly
Poland	430	Warszawa
Poland	428	Wroclaw
Romania	574	Bucuresti
Romania	572	Cluj-Napoca
Romania	576	Sibiu
Romania	580	Suceava
Romania	570	Timisoara
Romania	577	Timisoara
Russian Federation	443	Kazan
Russian Federation	444	Kazan
Russian Federation	442	Moscow
Russian Federation	449	Moscow
Russian Federation	440	Smolensk
Russian Federation	441	St. Petersburg
Russian Federation	446	St. Petersburg
Russian Federation	447	Voronezh
Serbia	464	Belgrade
Serbia	460	Kragujevac
Serbia	461	Novi Beograd
Serbia	462	Novi Sad
Serbia	463	Novi Sad
Slovakia	470	Bardejov
Slovakia	473	Nitra
Slovakia	472	Nove Zamky
Slovenia	670	Ljubljana
Taiwan	220	Changhua
Taiwan	222	Taichung
Taiwan	224	Taipei
Thailand	232	Bangkok
Thailand	236	Bangkoknoi
Thailand	231	Muang
Thailand	233	Muang
Thailand	235	Pathumwan
Thailand	230	Ratchathewi
Ukraine	602	Dnipropetrovsk
Ukraine	606	Kiev
Ukraine	682	Uzhgorod
Ukraine	603	Vinnitsa
United Kingdom	514	Birmingham
United Kingdom	515	Birmingham
United Kingdom	511	Leeds
United States	103	Atlanta	Georgia
United States	127	Boulder	Colorado
United States	102	Charlotte	North Carolina
United States	122	Dallas	Texas
United States	640	Eugene	Oregon
United States	115	Las Vegas	Nevada
United States	124	Lexington	Kentucky
United States	112	Louisville	Kentucky
United States	105	Orlando	Florida
United States	114	Seattle	Washington
United States	121	Shreveport	Louisiana
United States	117	Tampa	Florida
United States	101	Tomball	Texas

Sponsors (1)

Lead Sponsor	Collaborator
UCB Pharma

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  Colombia,  Croatia,  Czechia,  Estonia,  Georgia,  Hungary,  Israel,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Montenegro,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  Slovenia,  Taiwan,  Thailand,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Partial Onset Seizure (POS) Frequency Per 28 Days From Baseline to the Maintenance Period	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.	Baseline to Week 16 (or last value on treatment)
Secondary	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	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.	Baseline to Week 16 (or last value on treatment)
Secondary	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	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.	Baseline to Week 16 (or last value on treatment)
Secondary	Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods)	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.	Baseline to Week 16 (or last value on treatment)
Secondary	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)	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.	Baseline to Week 16 (or last value on treatment)
Secondary	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)	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.	Baseline to Week 16 (or last value on treatment)
Secondary	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)	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.	Baseline to Week 16 (or last value on treatment)
Secondary	Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Simple Partial Seizures	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.	Baseline to Week 16 (or last value on treatment)
Secondary	Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Complex Partial Seizures	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.	Baseline to Week 16 (or last value on treatment)
Secondary	Change in Partial Onset Seizure Frequency Per 28 Days From Baseline to the Entire Treatment (ie, Titration+Maintenance Periods) for Secondary Generalized Seizures	The POS frequency is standardized to a 28-day duration. Negative values indicate improvement from Baseline.	Baseline to Week 16 (or last value on treatment)
Secondary	Proportion of Seizure Free Days During the Maintenance Period for Subjects Who Completed the Maintenance Period	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.	Week 7 to Week 16
Secondary	Proportion of Subjects Who Achieved "Seizure Free" Status (Yes/no) for Subjects Who Completed the Maintenance Period	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.	Week 7 to Week 16

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