A Study to Assess the Safety and Efficacy of Lacosamide Versus Placebo (a Pill Without Active Medication) in Patients With Idiopathic Generalised Epilepsy Who Are Already Taking Anti-epileptic Medications

Epilepsy Clinical Trial

— VALOR  

Official title:

A Double-blind, Randomized, Placebo-controlled, Parallel-Group, Multicenter Study to Evaluate the Efficacy and Safety of Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02408523
• Other study ID #: SP0982
• Secondary ID: 2011-003100-21
• Status: Completed
• Phase: Phase 3
• Start date: April 2015
• Est. completion date: June 2019

Study information

• Verified date: November 2020
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluating efficacy & safety of lacosamide versus Placebo in a blinded fashion as add-on Therapy for Primary Generalized Tonic-clonic (PGTC) seizures in subject 4 years of age or greater with idiopathic generalized epilepsy currently taking 1 to 3 antiepileptic drugs. Maximum duration of study drug administration is 28 weeks. Eligible subjects may choose to enter the open-label extension study after completion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 242
• Est. completion date: June 2019
• Est. primary completion date: April 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

Inclusion Criteria:

• Subject with a confirmed diagnosis at least 24 weeks prior to Visit 1 and a disease onset prior to 30 years of age, consistent with idiopathic generalized epilepsy (IGE) experiencing primary generalized tonic-clonic (PGTC) seizures (Type IIE) that are classifiable according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures (ILAE, 1981)

• Subject has >=3 PGTC seizures during the 16-week Combined Baseline (12-week Historical Baseline plus 4-week Prospective Baseline)

• If a brain magnetic resonance imaging (MRI)/computed tomography (CT) scan has been performed, there must be no evidence of any progressive abnormality or any lesion likely to be associated with partial-onset seizures

• Subject has been maintained on a stable dose regimen of 1 to 2 non-benzodiazepine marketed antiepileptic drugs (AEDs) with no benzodiazepine AEDs OR 1 benzodiazepine marketed AED with 1 to 2 non benzodiazepine marketed AEDs for at least 28 days prior to Visit 1 with or without additional concurrent stable vagus nerve stimulation (VNS)

• Subjects are required to have had an electroencephalogram (EEG) report consistent with idiopathic generalized epilepsy (eg, generalized 3Hz epileptiform discharges and a normal EEG background) confirmed by a Central Reviewer

Exclusion Criteria:

• Subject is receiving any investigational drugs or using any experimental devices in addition to Lacosamide (LCM)

• Subject meets the withdrawal criteria for SP0982 or is experiencing an ongoing serious adverse event (SAE)

• Subject has an active suicidal ideation as indicated by a positive response ('Yes') to either Question 4 or Question 5 of the 'Since Last Visit' version of the Columbia-Suicide Severity Rating Scale (C-SSRS)

• Subject has >=2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (>=1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin <35%)

For randomized subjects with a Baseline result >ULN for ALT, AST, ALP, or total bilirubin, a Baseline diagnosis and/or the cause of any clinically meaningful elevation must be understood and recorded in the electronic case report form (eCRF).

If subject has >ULN ALT, AST, or ALP that does not meet the exclusion limit at screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing clinically relevant increase. In case of a clinically relevant increase, inclusion of the subject must be discussed with the Medical Monitor.

Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated once for confirmation. This includes re-screening.

Related Conditions & MeSH terms

• Epilepsy
• Seizures

Intervention

Drug:
• Lacosamide Tablet
Active Substance: Lacosamide Pharmaceutical Form: Film-coated Tablet Concentration: 50 mg Route of Administration: Oral use
• Lasosamide Oral Solution
Active Substance: Lacosamide Pharmaceutical Form: Oral Solution Concentration: 10 mg/ml Route of Administration: Oral use

Other:
• Placebo Tablet
Active Substance: Placebo Pharmaceutical Form: Film-coated Tablet Concentration: 50 mg Route of Administration: Oral use
• Placebo Oral Solution
Active Substance: Placebo Pharmaceutical Form: Oral Solution Concentration: 10 mg/ml Route of Administration: Oral use

Locations

Country	Name	City	State
Australia	Sp0982 980	Chatswood
Australia	Sp0982 985	Heidelberg
Australia	Sp0982 981	Parkville	Victoria
Australia	Sp0982 986	Parkville
Belgium	Sp0982 201	Brussels
Belgium	Sp0982 202	Gent
Belgium	Sp0982 200	Leuven
Brazil	Sp0982 181	Curitiba
Brazil	Sp0982 180	Florianópolis
Brazil	Sp0982 186	Passo Fundo
Brazil	Sp0982 185	Porto Alegre
Brazil	Sp0982 188	Rio De Janeiro
Brazil	Sp0982 183	São Paulo
Brazil	Sp0982 184	São Paulo
Bulgaria	Sp0982 500	Blagoevgrad
Bulgaria	Sp0982 501	Sofia
China	Sp0982 971	Beijing
China	Sp0982 976	Changchun
China	Sp0982 975	Chongqing
China	Sp0982 097	Fuzhou
China	Sp0982 973	Hangzhou
China	Sp0982 972	Shanghai
Czechia	Sp0982 550	Ostrava poruba
Czechia	Sp0982 553	Praha
Czechia	Sp0982 556	Praha
Czechia	Sp0982 552	Zlín
France	Sp0982 255	Bron
France	Sp0982 252	Lille Cedex
France	Sp0982 251	Nancy
France	Sp0982 250	Rennes Cedex 9
Germany	Sp0982 305	Berlin
Germany	Sp0982 303	Erlangen
Germany	Sp0982 314	Freiburg
Germany	Sp0982 311	Marburg
Germany	Sp0982 302	Muenchen
Hungary	Sp0982 600	Budapest
Hungary	Sp0982 603	Szeged
Israel	Sp0982 850	Re?ovot
Israel	Sp0982 851	Tel HaShomer
Italy	Sp0982 351	Torino
Japan	Sp0982 907	Asaka
Japan	Sp0982 906	Fukuoka-shi
Japan	Sp0982 910	Gifu
Japan	Sp0982 903	Hamamatsu
Japan	Sp0982 902	Hiroshima
Japan	Sp0982 913	Itami
Japan	Sp0982 912	Kagoshima
Japan	Sp0982 914	Kodaira
Japan	Sp0982 909	Kokubunji
Japan	Sp0982 901	Niigata
Japan	Sp0982 911	Omura
Japan	Sp0982 900	Sapporo
Japan	Sp0982 908	Shinjuku-Ku
Japan	Sp0982 904	Shizuoka
Korea, Republic of	Sp0982 940	Daegu
Korea, Republic of	Sp0982 941	Seoul
Korea, Republic of	Sp0982 944	Seoul
Mexico	Sp0982 161	Guadalajara
Poland	Sp0982 657	Czestochowa
Poland	Sp0982 655	Gdansk
Poland	Sp0982 658	Gdynia
Poland	Sp0982 652	Gliwice
Poland	Sp0982 651	Katowice
Poland	Sp0982 653	Katowice
Poland	Sp0982 654	Katowice
Poland	Sp0982 656	Tyniec Maly
Poland	Sp0982 650	Warszawa
Poland	Sp0982 659	Warszawa
Portugal	Sp0982 451	Lisboa
Romania	Sp0982 704	Iasi
Romania	Sp0982 707	Iasi
Romania	Sp0982 700	Timisoara
Russian Federation	Sp0982 757	Ekaterinburg
Russian Federation	Sp0982 750	Kazan
Russian Federation	Sp0982 758	Pyatigorsk
Russian Federation	Sp0982 755	Saint Petersburg
Russian Federation	Sp0982 756	Saint Petersburg
Russian Federation	Sp0982 752	Samara
Russian Federation	Sp0982 753	Smolensk
Slovakia	Sp0982 821	Bardejov
Slovakia	Sp0982 823	Hlohovec
Spain	Sp0982 402	Barcelona
Spain	Sp0982 406	Córdoba
Spain	Sp0982 407	Madrid
Spain	Sp0982 404	Málaga
Spain	Sp0982 403	Sevilla
Taiwan	Sp0982 961	Taichung
Taiwan	Sp0982 960	Taipei
United States	Sp0982 028	Alabaster	Alabama
United States	Sp0982 053	Austin	Texas
United States	Sp0982 007	Bethesda	Maryland
United States	Sp0982 015	Boise	Idaho
United States	Sp0982 031	Colorado Springs	Colorado
United States	Sp0982 036	Danbury	Connecticut
United States	Sp0982 035	Denver	Colorado
United States	Sp0982 025	Golden Valley	Minnesota
United States	Sp0982 050	Greenville	Texas
United States	Sp0982 034	Houston	Texas
United States	Sp0982 018	Irvine	California
United States	Sp0982 011	Jacksonville	Florida
United States	Sp0982 005	Little Rock	Arkansas
United States	Sp0982 023	Madison	Wisconsin
United States	Sp0982 009	New Orleans	Louisiana
United States	Sp0982 043	New York	New York
United States	Sp0982 013	Panama City	Florida
United States	Sp0982 021	Peoria	Illinois
United States	Sp0982 002	Port Charlotte	Florida
United States	Sp0982 027	Renton	Washington
United States	Sp0982 029	Saint Louis	Missouri
United States	Sp0982 038	San Antonio	Texas
United States	Sp0982 047	San Antonio	Texas
United States	Sp0982 008	Santa Monica	California
United States	Sp0982 045	Springfield	Illinois
United States	Sp0982 010	Waldorf	Maryland
United States	Sp0982 042	Wellington	Florida

Sponsors (2)

Lead Sponsor	Collaborator
UCB BIOSCIENCES, Inc.	Pharmaceutical Research Associates

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Bulgaria,  China,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to the Second Primary Generalized Tonic Clonic (PGTC) Seizure During the 24-week Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)	The primary efficacy variable was the time to the second primary generalized tonic clonic seizure (PGTCS) during the 24-week Treatment Period. Relative difference between groups (Lacosamide vs Placebo) was expressed as Hazard Ratio.; The indicated measured values are the observed number of events of second PGTCS in the treatment period which form the basis of the statistical analysis of the time to event analysis.; The hazard ratio compares 2 treatment groups for the times to a specified number of events (125) for the combined treatment groups, and so both the number of events and the times until those events pertain to the computation of the hazard ratio.; A Hazard Ratio below 1 indicates time to second PGTCS was improved for LCM compared to Placebo.	During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Secondary	Percentage of Participants With Seizure Freedom for Primary Generalized Tonic Clonic (PGTC) Seizures During the 24-week Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)	A seizure-free day from primary generalized tonic clonic seizures (PGTCS) was defined as a day where no PGTCS were reported in the seizure diary and PGTCS were assessed, which was estimated using Kaplan-Meier (KM) methods.	During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Secondary	Time to the First Primary Generalized Tonic Clonic (PGTC) Seizure During the Treatment Period From Visit 2 (Week 0) to Visit 10 (Week 24)	The secondary efficacy variable was the time to the first primary generalized tonic clonic seizure (PGTCS) during the 24-week Treatment Period. Relative difference between groups (Lacosamide vs Placebo) was expressed as Hazard Ratio.; The indicated measured values are the observed number of events of first PGTCS in the treatment period which form the basis of the statistical analysis of the time to event analysis.; The hazard ratio compares 2 treatment groups for the times to the number of events for the combined treatment groups, and so both the number of events and the times until those events pertain to the computation of the hazard ratio.; A Hazard Ratio below 1 indicates time to second PGTCS was improved for LCM compared to Placebo.	During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)
Secondary	Percentage of Participants With at Least One Adverse Event (AE) as Reported Spontaneously by the Subject and/or Caregiver or Observed by the Investigator	An AE was any untoward medical occurrence in a patient or clinical investigation study participant administered a pharmaceutical product that did not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational medicinal product (IMP), whether or not related to the IMP.	From Visit 1 (Week -4) to End of Study Period (up to Week 36)
Secondary	Plasma Concentrations of Lacosamide	Lacosamide plasma concentration was expressed in micrograms per milliliter (µg/mL).; Means and standard deviation (SD) were only calculated if at least 2/3 of the concentrations were quantified at the respective timepoint. Values Below Limit of Quantification (BLQ) were replaced by value of 0 in calculations of means and SDs.	During the Treatment Period from Visit 2 (Week 0) to Visit 10 (Week 24)

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