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 (VALOR)

UCB

Status and phase: Completed; Phase 3

Conditions: Epilepsy

Treatments: Other: Placebo Oral Solution; Drug: Lacosamide Tablet; Drug: Lasosamide Oral Solution; Other: Placebo Tablet

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02408523

SP0982

2011-003100-21 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 242 patients

Sex: All

Ages: 4+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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242 participants in 2 patient groups, including a placebo group

Lacosamide

Experimental group

Description:

Lacosamide 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day are allowed. Maximal dose 400 mg/day for adult subjects and pediatric subjects \>= 50 kg. Lacosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric subjects \< 30 kg.) Lasosamide oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric subjects 30 kg to \< 50 kg.)

Treatment:

Drug: Lacosamide Tablet

Drug: Lasosamide Oral Solution

Placebo

Placebo Comparator group

Description:

Placebo 50 mg tablets: starting with 100 mg/day at Week 1. Weekly increase in steps of 50 mg or 100 mg/day are allowed. Maximal dose 400mg/day for adult subjects and pediatric subjects \>= 50kg. Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 12 mg/kg/day for pediatric subjects \< 30kg.) Placebo oral solution 10 mg/ml: starting with 2 mg/kg/day, titrations steps (1 mg/kg/day to 2 mg/kg/day; maximal dose 8 mg/kg/day for pediatric subjects 30kg to \< 50kg.)

Treatment:

Other: Placebo Oral Solution

Other: Placebo Tablet