Safety and Efficacy of Lacosamide as Additional Therapy in Patients Suffering From Epileptic Tonic-Clonic Seizures (VALUE)

• ClinicalTrials.gov Identifier: NCT02408549
• Recruitment Status: Active, not recruiting
• First Posted: April 3, 2015
• Last Update Posted: May 20, 2022
• Sponsor: UCB BIOSCIENCES, Inc.
• Information provided by (Responsible Party): UCB Pharma ( UCB BIOSCIENCES, Inc. )

Study Description

Brief Summary:

Assessment of long-term safety and efficacy of oral lacosamide (LCM) as an adjunctive therapy for uncontrolled primary generalized tonic-clonic seizures (PGTCS) in subjects >= 4 years of age with idiopathic generalized epilepsy (IGE). This study will enroll subjects from the LCM SP0982 [NCT02408523] study.

Condition or disease	Intervention/treatment	Phase
Epilepsy	Drug: Lacosamide Tablet; Drug: Lacosamide Oral Solution	Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 239 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter Extension Study to Evaluate the Long-term Safety and Efficacy of Lacosamide as Adjunctive Therapy for Uncontrolled Primary Generalized Tonic-Clonic Seizures in Subjects With Idiopathic Generalized Epilepsy
• Actual Study Start Date: August 2015
• Estimated Primary Completion Date: October 2023
• Estimated Study Completion Date: October 2023

Arms and Interventions

Arm

Intervention/treatment

Experimental: Lacosamide; Start dose SP982 completers at V1: LCM 10 mg/kg/day for pediatric subjects weighing <30 kg; LCM 8 mg/kg/day for pediatric subjects weighing ≥ 30kg to <50 kg; LCM 400 mg/day (200 mg bid) for adult subjects (≥18 years of age) or pediatric subjects weighing ≥50 kg SP982 Baseline failures at V1: LCM 2 mg/kg/day for pediatric subjects weighing <50 kg; LCM 100 mg/day (50 mg bid) for adult subjects (≥18 years of age) or pediatric subjects weighing ≥50 kg Oral solution (pediatric subjects <50 kg): Minimum LCM dose: 4 mg/kg/day; Maximum LCM dose: 12 mg/kg/day Tablets (pediatric subjects ≥50kg): Minimum LCM dose: 200 mg/day; Minimum LCM dose: 600 mg/day Tablets (adult subjects): Minimum LCM dose: 200 mg/day; Maximum LCM dose: 800 mg/day

Drug: Lacosamide Tablet; Active substance: Lacosamide; Pharmaceutical form: Tablet; Concentration: 50 mg and 100 mg; Route of Administration: oral administration; Other Names: Vimpat; LCM; Drug: Lacosamide Oral Solution; Active substance: Lacosamide; Pharmaceutical form: Oral solution; Concentration: 10 mg/ml; Route of Administration: Oral administration; Other Names: Vimpat; LCM

Outcome Measures

Primary Outcome Measures :

1. Number of subjects with treatment-emergent adverse events (TEAEs) over the duration of the Treatment Period [ Time Frame: During the Treatment Period (up to 5 years) ]
   Adverse Events will be reported spontaneously by the subject and/or caregiver or observed by the investigator.
2. Number of subjects withdrawn due to TEAEs [ Time Frame: During the Treatment Period (up to 5 years) ]
   Adverse Events will be reported spontaneously by the subject and/or caregiver or observed by the investigator.
3. Number of subjects with new appearance of absence and/or myoclonic seizures during the Treatment Period [ Time Frame: During the Treatment Period (up to 5 years) ]
   Incidence of new seizure types in the EP0012 Treatment Period for all subjects who haven't had that seizure type in combined baseline or history before taking lacosamide (LCM).
4. Number of subjects with an increase of up to 25% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
5. Number of subjects with an increase of >25% to 50% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
6. Number of subjects with an increase of >50% to 75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
7. Number of subjects with an increase of >75% in days with absence seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
8. Number of subjects with an increase of up to 25% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
9. Number of subjects with an increase of >25% to 50% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
10. Number of subjects with an increase of >50% to 75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
11. Number of subjects with an increase of >75% in days with myoclonic seizures per 28 days during the Treatment Period as compared to the Prospective Baseline (of study SP0982) [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
12. Percentage of subjects with at least 50% worsening in days with absence seizures [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]
13. Percentage of subjects with at least 50% worsening in days with myoclonic seizures [ Time Frame: From Visit 1 to End of Treatment Period (up to 5 years) ]

Secondary Outcome Measures :

1. Percentage of treatment-emergent marked abnormalities in hematology parameters [ Time Frame: During the study (up to 5 years) ]
2. Percentage of treatment-emergent marked abnormalities in chemistry parameters [ Time Frame: During the study (up to 5 years) ]
3. Percentage of treatment-emergent marked abnormalities in 12-lead electrocardiogram (ECGs) [ Time Frame: During the study (up to 5 years) ]
4. Percentage of treatment-emergent marked abnormalities in vital sign measurements [ Time Frame: During the study (up to 5 years) ]
5. Percent change in Primary Generalized Tonic-clonic seizure (PGTCS) frequency per 28 days from Combined Baseline [ Time Frame: From Combined Baseline until Termination Visit (up to 5 years) ]
   Percent change in PGTCS frequency per 28 days from Combined Baseline, where Combined Baseline is defined as the combined 12-week Historical Baseline and 4-week Prospective Baseline periods immediately prior to randomization in the parent study (SP0982).

Eligibility Criteria

• Ages Eligible for Study: 4 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

-Subject must have completed or be an eligible Baseline failure from the parent study (SP0982 [NCT02408523]). Note: Other subjects screened for SP0982 may be considered for roll-over to EP0012 if the investigator considers that the subject could benefit from treatment with open-label lacosamide (LCM) and based on prior discussion with and approval from the UCB Study Physician or representative

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 all subjects who entered EP0012 directly 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). Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated once for confirmation.

Contacts and Locations

Locations

United States, Arkansas

Ep0012 005

Little Rock, Arkansas, United States, 72205

United States, California

Ep0012 008

Santa Monica, California, United States, 90404

United States, Colorado

Ep0012 031

Colorado Springs, Colorado, United States, 80910

United States, Florida

Ep0012 042

Loxahatchee Groves, Florida, United States, 33470

Ep0012 013

Panama City, Florida, United States, 32405

Ep0012 002

Port Charlotte, Florida, United States, 33952

United States, Idaho

Ep0012 015

Boise, Idaho, United States, 83702

United States, Illinois

Ep0012 021

Peoria, Illinois, United States, 61637

United States, Minnesota

Ep0012 025

Golden Valley, Minnesota, United States, 55422

United States, New York

Ep0012 043

New York, New York, United States, 10016

United States, Texas

Ep0012 053

Austin, Texas, United States, 78758

Ep0012 050

Greenville, Texas, United States, 75401

Ep0012 034

Houston, Texas, United States, 77005

Ep0012 038

San Antonio, Texas, United States, 78229

United States, Washington

Ep0012 027

Renton, Washington, United States, 98057

United States, Wisconsin

Ep0012 023

Madison, Wisconsin, United States, 53715

Australia

Ep0012 980

Chatswood, Australia

Ep0012 985

Heidelberg, Australia

Ep0012 986

Melbourne, Australia

Ep0012 981

Parkville, Australia

Brazil

Ep0012 181

Curitiba, Brazil

Ep0012 180

Florianopolis, Brazil

Ep0012 186

Passo Fundo, Brazil

Ep0012 185

Porto Alegre, Brazil

Ep0012 188

Rio de Janeiro, Brazil

Ep0012 183

Sao Paulo, Brazil

Bulgaria

Ep0012 500

Blagoevgrad, Bulgaria

Ep0012 501

Sofia, Bulgaria

China

Ep0012 971

Beijing, China

Ep0012 976

Changchun, China

Ep0012 374

Nanchang, China

Ep0012 972

Shanghai, China

Czechia

Ep0012 550

Ostarva Poruba, Czechia

Ep0012 553

Prague, Czechia

Ep0012 556

Praha 11, Czechia

Ep0012 552

Zlin, Czechia

France

Ep0012 255

Bron, France

Ep0012 252

Lille Cedex, France

Ep0012 251

Nancy, France

Germany

Ep0012 303

Erlangen, Germany

Ep0012 314

Freiburg, Germany

Ep0012 311

Marburg, Germany

Hungary

Ep0012 062

Budapest, Hungary

Ep0012 600

Budapest, Hungary

Ep0012 603

Szeged, Hungary

Israel

Ep0012 850

Reẖovot, Israel

Ep0012 851

Tel Hashomer, Israel

Italy

Ep0012 351

Torino, Italy

Japan

Ep0012 906

Fukuoka-Shi, Fukuoka, Japan

Ep0012 910

Gifu, Japan

Ep0012 903

Hamamatsu, Japan

Ep0012 902

Hiroshima, Japan

Ep0012 912

Kagoshima, Japan

Ep0012 914

Kodaira-City, Japan

Ep0012 909

Kokubunji-shi, Japan

Ep0012 901

Niigata-City, Japan

Ep0012 900

Sapporo-City, Japan

Ep0012 908

Shinjuku, Japan

Ep0012 911

Ōmura, Japan

Korea, Republic of

Ep0012 940

Daegu, Korea, Republic of

Ep0012 941

Seoul, Korea, Republic of

Ep0012 944

Seoul, Korea, Republic of

Mexico

Ep0012 161

Guadalajara, Mexico

Poland

Ep0012 657

Czestochowa, Poland

Ep0012 655

Gdansk, Poland

Ep0012 652

Gliwice, Poland

Ep0012 651

Katowice, Poland

Ep0012 653

Katowice, Poland

Ep0012 654

Katowice, Poland

Ep0012 656

Tyniec Maly, Poland

Ep0012 650

Warszawa, Poland

Ep0012 659

Warszawa, Poland

Portugal

Ep0012 451

Lisboa, Portugal

Romania

Ep0012 704

Iasi, Romania

Ep0012 700

Timisoara, Romania

Russian Federation

Ep0012 757

Ekaterinburg, Russian Federation

Ep0012 750

Kazan, Russian Federation

Ep0012 758

Pyatigorsk, Russian Federation

Ep0012 756

Saint Petersburg, Russian Federation

Ep0012 752

Samara, Russian Federation

Ep0012 755

Sankt Petersburg, Russian Federation

Slovakia

Ep0012 821

Bardejov, Slovakia

Ep0012 823

Hlohovec, Slovakia

Spain

Ep0012 402

Barcelona, Spain

Ep0012 406

Cordoba, Spain

Ep0012 407

Madrid, Spain

Ep0012 403

Sevilla, Spain

Taiwan

Ep0012 961

Taichung, Taiwan

Ep0012 960

Taipei, Taiwan

Sponsors and Collaborators

UCB BIOSCIENCES, Inc.

Investigators

• Study Director: UCB Cares; 001 844 599 2273 (UCB)

More Information

• Responsible Party: UCB BIOSCIENCES, Inc.
• ClinicalTrials.gov Identifier: NCT02408549
• Other Study ID Numbers: EP0012; 2012-001770-29 ( EudraCT Number )
• First Posted: April 3, 2015
• Last Update Posted: May 20, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.
• URL: https://www.Vivli.org

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by UCB Pharma ( UCB BIOSCIENCES, Inc. ):

Lacosamide; Vimpat; Epilepsy; Children; Primary Generalized Tonic-Clonic seizures; Idiopathic Generalized Epilepsy; Adults

Additional relevant MeSH terms:

Epilepsy; Seizures; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Lacosamide; Anticonvulsants; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action