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- Dr. Rajnish Dhediya [SYR] Guide: Dr. Shirish Joshi
Recent advances in the
treatment of Epilepsy
• Term epilepsy is derived from the Greek word “Epilamvanein or Epilepsia”, which means ‘to be seized’, ‘to be taken hold of’, or ‘to be attacked’
• Epilepsy: A condition in which a person has recurrent seizures due to chronic, underlying process
Characterized by,
- Recurrent seizures
- Loss of consciousness
- With or without body movements
• Seizure: “Paroxysmal event due to abnormal, excessive, hyper synchronous neuronal activity in the brain.”
Longo, Fauci, Kasper, Houser, Jamson, Loscalzo.Harrison’s principle of internal medicine:18 th edition, volume 1;Chapter-369
Talking about numbers….
• Second most common neurological disease
• 50 million people worldwide have epilepsy,
• 80% of epilepsy cases worldwide are found in developing regions
In India,
Incidence rate: 27.27 cases per year per 100,000 persons
Prevalence rate: 572.8 cases per 100,000 persons
1,81,000 new cases each yearDrug therapy successful in only 50%
Modified ILAE Classification
Partial Generalized
Seizure
Secondary gen.
TonicClonicTonic-clonicAbsenceAtonicMyoclonicAtypical absenceInfantile spasms
Complex Simple
Motor
Sensory
Autonomic
PsychicPanayiotopoulos C P. The new ILAE report on terminology and concepts for organization of epileptic seizures: a clinician's critical view and contribution. Epilepsia. 2011 Dec;52(12):2155-60
Pathophysiology of seizures
• No pathognomic lesion
• Hallmark is rhythmic and repetitive hyper synchronous discharge of neurons
• The regular low frequency neuronal discharges are replaced by bursts of high frequency discharges, usually followed by periods of inactivity.
• The diagnosis of epilepsy is mainly clinical, EEG and other investigations help, but cannot conclusively confirm or refute the diagnosis
Seizure SequenceBurst of action potentials
Hyper synchronization
Seizure Propagation
Seizure Initiation
Pathophysiology of seizures
Hyper-excitable state
Decreased inhibitory input:
GABA
Increased excitatory input:
GlutamateVoltage-gated ion channels in favour
of excitation
Therapeutic targets...
Lourence L.Brunton, Brause A .Chabner, Bjorn K,Knollmann, The pharmacological basis of therapeutics:12 th edition, Section II. Neuropharmacology, Chapter 21. Pharmacotherapy of the Epilepsies
Drugs acting on Na+ channel
Drugs acting on Ca+2 channels
Drugs enhancing GABAergic transmission
Antiepileptic drugs• Efficacy known• Less expensive• Easily available
• Hepatic enzyme induction/ inhibition
• Drug-drug interaction• Category D• Alters hormonal & vitamin levels
Antiepileptic drugs
Newer Antiepileptic drugs
Joseph Sirven, Katherine Noe, Mathew Hoerth, Joseph Drazkowski. Antiepileptic Drugs 2012: Recent Advances and Trends. Mayo Clinic Proceedings Vol 87, Issue 9 (879–889)
Newer Antiepileptic drugsDrugs Mechanism of
actionFDA approved indication
Lamotrigine Inhibits voltage sensitive sodium channels Inhibits synaptic release of glutamate
as adjunctive therapy of partial seizures in patients greater than or equal to 2 years of age and Primary GTC in patients ≥ 13 years of age
Levetiracetam Binds to synaptic vesicle protein SV2A and impedes nerve conduction
Refractory Partial seizuresRefractory JME
Gabapentin Binds to α2δ subunit of voltage gated calcium channels
Partial seizure with or without secondary generalization
Drugs Mechanism of action FDA approved indication
Lacosamide Sodium channel modulation
Add-on for partial epilepsy
Rufinamide Sodium channel modulation
Lennox-Gastaut syndrome in children 4 years and older and adultsAtonic seizures
Zonisamide Inhibition of sodium channels & T type of calcium channel currentsDecreases GABA uptake & increases glutamate uptake
Focal seizure
Vigabatrin Irreversible inhibitor of GABA transaminase
Infantile spasmsAs an adjunctive for refractory partial epilepsy
Newer Antiepileptic drugs
Advantages of Newer AEDs:
Greater tolerability
Fewer side effects
Fewer drug interactions
Lower rate of relapse after withdrawal
Fewer idiosyncratic reactions
Minimal influence on metabolic pathways
Category C
Joseph Sirven, Katherine Noe, Mathew Hoerth, Joseph Drazkowski. Antiepileptic Drugs 2012: Recent Advances and Trends. Mayo Clinic Proceedings Vol 87, Issue 9 (879–889)
Current treatmentSeizure type First line treatment Second line treatment
Partial seizures CarbamazepineLamotrigineOxcarbazepineLevetiracetam
TopiramateValproateClobazamZonisamide
Generalized seizures
Tonic-clonic Sodium ValproateCarbamazepine
LamotrigineClobazam
Absence EthosuximideSodium valproate
ClobazepamLamotrigine
Atypical absence ClobazepamClobazam
LamotrigineCarbamazepine
Myoclonic Sodium valproateClonazepam
LevitiracetamTopiramate
Need For Better AED’s ??
• No evidence that any new AED was superior in efficacy to old AEDs
Eg. CBZ and VPA in efficacy in well-controlled trials of recent-onset epilepsy.
• Although seizure control may have improved in rare epilepsies (Vigabatrin for West-Syndrome , Felbamate for LGS), but , seizure control has not improved dramatically in the last 30 years for common seizures (focal, myoclonic and absence)
• Further, one in three patients has drug resistant seizures.
Recent advances…
FDA approved drugs
New applications of existing drugs
New formulations in
pipeline
Drugs in pipeline
Recent FDA approvals
Clobazam
• Acts by potentiation of GABAnergic transmission via binding to GABA-A receptor
A benzodiazepine with low tendency to produce sedation Lower incidence of loss of therapeutic effect over time, rendering it
appropriate for long term management
• Oct 2011: FDA approved for Clobazam as adjunctive treatment for seizures associated with Lennox-Gestaut syndrome in adults and children 2 years of age and older in a dose of 5-40 mg/day.
Effectiveness was established in two multi-centre controlled studies.
• Most common adverse effects: sedation, lethargy and fatigue
In Dec 2013, FDA issued warning against serious skin
reactions that can result in permanent harm and death and
approved label changes
Ng YT, Conry JA, Drummond R, Stolle J, Weinberg MA; OV-1012 Study Investigators. Randomized, phase III study results of Clobazam in Lennox-Gastaut syndrome. Neurology. 2011 Oct 11;77(15):1473-81
Ezogabine
• First neuronal potassium channel opener developed for the
treatment of epilepsy
Acts by enhancement of potassium currents mediated by KCNQ ion
channels, thereby reducing hyper excitability
Also potentiates GABA-A receptors via activation of beta 1 & beta 2
subtype of GABA receptor
Also, weakly blocks sodium and calcium channels
Nov 2011: FDA approved Ezogabine as an adjunctive treatment in
refractory partial-onset seizures based on RESTORE I & II trials
Owen RT Ezogabine: a novel antiepileptic as adjunctive therapy for partial onset seizures. Drugs Today 2010 Nov;46(11):815-22
RESTORE 1 & 2(Retigabine Efficacy and Safety Trials for Partial Onset Epilepsy Study)
Brodie MJ, Lerche H, Gil-Nagel A, Elger C, Hall S, Shin P, Nohria V, Mansbach H; RESTORE 2 Study Group. Efficacy and safety of adjunctive ezogabine (retigabine) in refractory partial epilepsy. Neurology. 2010 Nov 16;75(20):1817-24
French JA, Abou-Khalil BW, Leroy RF, Yacubian EM, Shin P, Hall S, Mansbach H, Nohria V; RESTORE 1/Study Investigators. Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy. Neurology. 2011 May 3;76(18):1555-63
Ezogabine (Retigabine)• Absorption is unaffected by food with an absolute bioavailability of
50–60%• Peak plasma concentration within 1.5 h and half life is 8 – 11 hours
• Not metabolized by the cytochrome P450 system, so minimal drug interactions seen, as below,
Phenytoin & Carbamazepine decrease Ezogabine concentration Ezogabine inhibits renal clearance of digoxin Alcohol can increase serum Ezogabine concentrations
Serious adverse effects include urinary retention, neuropsychiatric symptoms and QT-interval lengthening that need careful monitoring
French J A et al. Randomized, double-blind, placebo-controlled trial of ezogabine (retigabine) in partial epilepsy. Neurology.2011 May 3; 76(18): 1555-63
Oxcarbazepine ER• Acts by blockade of voltage sensitive sodium channels Less potent enzyme inducer than carbamazepine
• Oct 2012: FDA approved a once-daily extended-release formulation as an adjunctive therapy for partial seizures in adults and in children > 6 years
• Dose: 1200 – 2400 OD on empty stomach
• PROSPER study, a multicentre, randomized, double-blind trial in 366 patients with refractory partial epilepsy showed efficacy
• Most common adverse effects include headache, dizziness and diplopia Rare and Serious adverse effects are hyponatremia and suicidal ideation
French JA, Baroldi P, Brittain ST, Johnson JK; PROSPER Investigators Study Group. Efficacy and safety of extended-release oxcarbazepine (Oxtellar XR™) as adjunctive therapy in patients with refractory partial-onset seizures: a randomized controlled trial. Acta Neurol Scand. 2014 Mar;129(3):143-53
Eslicarbazepine• Third generation AED
• S-licarbazepine: effective component of carbamazepine with,
fewer cognitive and psychiatric adverse effects
crosses BBB more effectively
lacks a toxic epoxide
minimal interaction with the cytochrome P450 liver enzymes
Elger et al. showed less incidence of hyponatremia compared to
oxcarbazepine
Elinor Ben-Menachem. Eslicarbazepine Acetate: A Well-Kept Secret? Epilepsy Curr. Jan 2010; 10(1): 7–8
• Acts by blockade of fast acting voltage gated sodium channels
• Nov 2013: US FDA approved as an adjunctive treatment for partial onset seizures
• Based on 3 randomized, double blind, multi-centre trials in 1049 patients with partial onset seizures
• Dose: 400-1200 mg/day ; once daily dosing
• Most adverse effects include headache, nausea, ataxia, tremors
Eslicarbazepine
Gil-Nagel A, Elger C, Ben-Menachem E, Halász P, Lopes-Lima J, Gabbai AA, Nunes T, Falcão A, Almeida L, da-Silva PS. Efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: integrated analysis of pooled data from double-blind phase III clinical studies. Epilepsia. 2013 Jan;54(1):98-107
Parampanel• First-in-class drug, a highly selective, non competitive AMPA type
glutamate receptor antagonist
• Nov 2012: FDA approved for treatment of refractory partial-onset seizures in patients 12 years and older,
based on 3 clinical trials in 1037 adults and adolescents which showed reduced seizure frequency
Dose: 4 – 12 mg OD
• Boxed warning about the risk for serious neuropsychiatric events
• Common adverse effects include dizziness, fatigue, irritability, anxiety, aggression, etc
Steinhoff BJ, Ben-Menachem E, Ryvlin P, Shorvon S, Kramer L, Satlin A, Squillacote D, Yang H, Zhu J, Laurenza A. Efficacy and safety of adjunctive perampanel for the treatment of refractory partial seizures: a pooled analysis of three phase III studies. Epilepsia. 2013 Aug;54(8):1481-9
Topiramate –extended release
Blockage of voltage-dependent sodium channels
Augmentation of the activity of the neurotransmitter GABA
Antagonism of the AMPA/ kainate subtype of the glutamate
receptor
• March 2014: US FDA approved
As monotherapy for focal seizure and primary GTC in patients >
10 years and,
As an adjunctive therapy in patients > 2 years for focal seizures,
primary GTC and seizures associated with Lennox-Gestaut
syndrome.
• Phase III PREVAIL study in 249 patients with partial-onset seizures,
• PREVAIL study demonstrated - efficacy - improved seizure control - Less cognitive side effects
• Dose: 400 mg OD
• Adverse effects include dizziness, weight loss, paraesthesia etc.
Topiramate –extended release
Chung SS, Fakhoury TA, Hogan RE, Nagaraddi VN, Blatt I, Lawson B, Arnold S, Anders B, Clark AM, Laine D, Meadows RS, Halvorsen MB; PREVAIL Study Group. Once-daily USL255 as adjunctive treatment of partial-onset seizures: randomized phase III study. Epilepsia. 2014 Jul;55(7):1077-87
Drugs in pipeline
Drugs decreasing neuronal excitation
A. Blockade of sodium channel• Brivaracetam• Carisbamate
B. Inhibition of glutamate release/ AMPA antagonist• NS 1209• BGG 492
Drugs enhancing neuronal inhibition
• Ganalaxone
• Stiripentol
• CPP 115
• Valrocemide
Drugs in pipeline
Drugs in pipelineNovel agents
1. Anti-inflammatory: Belnacasan (VX 765)
2. Pro-drug of Valproic acid: SPD 421, Valnoctamide
3. Chloride importer blockade: Bumetanide
4. Drugs acting on potassium channels
• YKP 3089
• ICA 105665
5. Melatonin
6. 5HT receptor agonist: Naluzotan
Brivaracetam
• Levetiracetam analogue
• 10-fold greater affinity for synaptic vesicle protein 2α (SV2α)
ligand than does Levetiracetam
• Additional sodium channel-blocking properties
• Preclinical study suggested potent and broad spectrum
antiepileptic activity
• Currently in phase III for partial onset seizure
Biton V, Berkovic SF, Abou-Khalil B, Sperling MR, Johnson ME, Lu S. Brivaracetam as adjunctive treatment for uncontrolled partial epilepsy in adults: a phase III randomized, double-blind, placebo-controlled trial. Epilepsia. 2014 Jan;55(1):57-66
Carisbamate (RWJ 333369)
• Novel neuromodulator
• Proposed mechanism of action: Inhibit voltage gated sodium channel & modest inhibition of voltage gated calcium channel
• Phase II study- adjunctive use in partial onset seizures showed efficacy at a well tolerated dose
• Phase III study in 2011 for focal seizure failed to demonstrate efficacy across the dose range assessed versus placebo.
A Study of the Effectiveness, Safety, and Tolerability of Carisbamate as Add-On Therapy in Patients With Partial Onset Seizures. http://clinicaltrials.gov/show/NCT00740623 (accessed 21 Nov 2014)
1. NS 1209AMPA antagonists
• Novel competitive AMPA antagonist
• Phase II study in patients with refractory status epilepticus failed to
reach study end point
2. BGG 492• Orally active AMPA antagonist
• Very favourable safety profile is evidence by a lack of
cardiovascular, phototoxic or teratogenicity potential
• Currently in phase II for focal seizure & photosensitive epilepsy
Global Journal of Medical Research: B Pharma, Drug Discovery, Toxicology and Medicine. Volume 14 Issue 4 Version 1.0 Year 2014
Ganaxolone
• A neurosteroid with ability to modulate neurotransmission
• Acts as positive allosteric modulator of γ-amino butyric acid GABA- A receptors
• Phase II (2009) trial: shown beneficial role in refractory focal seizure
• Currently in phase III for drug resistant focal seizure- Recruiting participants
Phase 3 Study of Adjunctive Ganaxolone in Adults With Drug-resistant Partial Onset Seizures, With Long-term Open-label Extension. http://www.clinicaltrials.gov/show/NCT01963208. (accessed 21 Nov 2014)
Pieribone VA, Tsai J, Soufflet C, Rey E, Shaw K, Giller E, Dulac O. Clinical evaluation of ganaxolone in pediatric and adolescent patients with refractory epilepsy. Epilepsia. 2007 Oct;48(10):1870-4
Stiripentol• Increase γ-amino butyric acid (GABA) levels in brain tissue
• Involves at least two independent neurochemical mechanisms: Inhibition of synaptosomal uptake of GABAInhibition of GABA transaminase
• Phase III- Childhood focal seizure-Failed to achieve primary end point
• Currently undergoing Expanded Access study for Dravet Syndrome or Sodium Channel Mutation Epileptic Encephalopathy
Chiron C1, Tonnelier S, Rey E, Brunet ML, Tran A, d'Athis P, Vincent J, Dulac O, Pons G. Stiripentol in childhood partial epilepsy: randomized placebo-controlled trial with enrichment and withdrawal design. J Child Neurol. 2006 Jun;21(6):496-502.
CPP 115• Analogue of Vigabatrin with favourable pharmacokinetics
• Acts by irreversible inhibition of GABA transaminase, enzyme
responsible for metabolism of inhibitory neurotransmitter GABA
• Superior efficacy in an infantile spasms model
• Minimal drug-drug interaction with good safety profile
• Received orphan drug designation for infantile spasms
• Phase I studies: well-tolerated at doses upto 500 mg
• Currently in Phase II for Refractory complex focal seizures
Briggs SW, Mowrey W, Hall CB, Galanopoulou AS. CPP-115, a vigabatrin analogue, decreases spasms in the multiple-hit rat model of infantile spasms. Epilepsia. 2014 Jan;55(1):94-102
A Safety, Tolerability and Pharmacokinetic Study of CPP-115. http://clinicaltrials.gov/show/NCT01493596 (accessed 20 Nov 2014)
Valrocemide
• Amide derivative of valproic acid
• Mechanism of action : Potentiation of gabanergic current by
binding to GABA receptor
• Phase I : Safe, Relative bioavailabily-88 %
• Phase II : showed efficacy of Valrocemide as an adjunctive
therapy in refractory epilepsy patients
• Phase III: Presently Ongoing in patients with refractory epilepsy
Hovinga CA. Valrocemide (Teva/Acorda). Curr Opin Investig Drugs. 2004 Jan;5(1):101-6.
Belnacasan (VX 765)
• Proposed involvement of inflammatory mechanisms in the
generation of epileptic discharges
• Belnacasan inhibits Interleukin converting enzyme/ Caspase 1 and
thereby production of cytokines
• Following exposure to pro-inflammatory stimuli, the release of IL-1β
in hippocampus is reduced, thereby preventing acute seizures
Lauren Walker, Graeme JS. Inflammation and Epilepsy: The Foundations for a New Therapeutic Approach in Epilepsy? Epilepsy Curr. 2012 Jan-Feb;12(1): 8–12
• Efficacy is confirmed in preclinical models
Phase IIa trial in drug-resistant partial epilepsy suggest that
Belnacasan is safe and well tolerated when administered
over a 6-week period
Phase IIb trial in patients with treatment-resistant epilepsy is
currently ongoing
Belnacasan (VX 765)
Study of VX-765 in Subjects With Treatment-resistant Partial Epilepsy. http://clinicaltrials.gov /ct2/show /NCT01048255. (accessed 18 Nov 2014)
• Phospholipid derivative of valproic acid
• It is a pro-drug based on Regulated activation of pro-drugs (RAP)
technology, to overcome unfavourable pharmacokinetics of
valproic acid
• Multinational phase II trials of SPD-421 as add-on therapy in the
treatment of complex partial seizures reported positive results
• Adverse effects are minimal compared to Valproate
Valnoctamide, an amide derivative of Valproate, has a potential in epilepsy and is currently being investigated in Phase I trials
Labiner DM. DP-VPA D-Pharm. Curr Opin Investig Drugs.2002 Jun; 3(6): 921-3
Bumetanide
• A loop diuretic, blocks the Na–K–2Cl co-transporter in neurons,
the concentration change making the action of GABA more
hyperpolarizing
• Preclinical studies have shown promising results
• A pilot study demonstrated reduction of seizure frequency in
adult patients with temporal lobe epilepsy
• A Phase I Study of Pharmacokinetics and Safety of Bumetanide
for Neonatal Seizures is currently ongoing
• Eftekhari S et al. Bumetanide reduces seizure frequency in patients with tempo al lobe epilepsy. Epilepsia. 2013 Jan; 54(1):9-12
• Wolfgang Lösche. Martin Puskarjov. Kai Kaila. Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments. Neuropharmacology. Vol. 69,June 2013, pg.62–74
Potassium channels modulators
YKP 3089
• Novel, broad spectrum anti-epileptic
• Mechanism of action is not yet defined, possibly act by
increased KCN Q 2/3 type of potassium current
• High safety margin in phase I study
• Phase II study is ongoing for focal seizures.
Meir Bialera, Svein I, Johannessen , René H. Levyd, Emilio Peruccae, Torbjörn Tomsonf, H. Steve White. Progress report on new antiepileptic drugs: Asummary of the Tenth Eilat Conference (EILAT X). Epilepsy Research (2010) 92, 89—124
Potassium channels modulators
ICA 105665
• Agonist of neuronal Kv7 potassium channels
• Phase I- Safe
• In 2010, a Phase 2, multi-centre study was terminated
following a SAE that occurred with the first subject dosed at
600 mg
A Study to Investigate the Effect of ICA-105665 in Photosensitive Epilepsy Patients. http://clinicaltrials.gov/show /NCT00979004 (accessed 18 Nov 2014)
Melatonin
• Baseline melatonin levels are low in patients with uncontrolled
epilepsy and increase markedly following seizures
• Melatonin modulates the electrical activity of neurons by reducing
glutamatergic and enhancing GABA-ergic neurotransmission and
experimental data indicates anticonvulsant properties of the
hormone
• ‘Pilot Study of Melatonin and Epilepsy’ completed in June 2014
Banach M. Gurdziel E. Jędrych M, Borowicz KK. Melatonin in experimental seizures and epilepsy. Pharmacol Rep. 2011; 63(1): 1-11
Naluzotan
• Orally active selective 5-HT-1A receptor partial agonist
• Proposed mechanism of epileptogenesis is reduced 5-HT-1A receptor binding
• Naluzotan acts by increasing neurotransmitter activity at 5HT-1A receptor, thereby reducing seizure incidence and severity
• Phase I study revealed Naluzotan as safe & well tolerated
• Currently, Phase 2 trial is ongoing in patients with epilepsy
New Formulations
Intranasal • diazepam • midazolam (USL 261)
Diazepam auto injection
Advantages:
Absorption from nasal mucosa
within 2 – 5 minutes
Rapid penetration into the
central nervous system
Studies reveal superiority over diazepam for quickness of response
and ease of administration
Cost effective and feasible to administer to adults as well
Intranasal formulations
Lesley K. Humphries. Lea S. Eiland. Treatment of Acute Seizures: Is Intranasal Midazolam a Viable Option? J P ediatr Pharmacol Ther. 2013 Apr-Jun; 18(2): 79–87
Midazolam (USL 261)
Phase II: Single doses up to 7.5mg were well-tolerated with no significant adverse events
ARTEMIS1: Phase 3 study to Evaluate the Safety and Efficacy of Intranasal Midazolam in Patients With Seizure Clusters is currently ongoing.
Diazepam
Phase I study showed intranasal diazepam is safe with a bioavailability of 97%
Intranasal formulations
Study to Evaluate the Safety and Efficacy of USL261 (Intranasal Midazolam) in Patients with Seizure Clusters (ARTEMIS1). http://www.clinicaltrials.gov /show /NCT01390220. (accessed 20 Nov 2014)Thakker A1, Shanbag P. A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures. J Neurol. 2013 Feb;260(2):470-4
Diazepam auto injection • Pen-like device that injects medication intramuscularly
• Phase I & II : Safe & effective at stopping acute repetitive or cluster seizures
• July 2014: Phase III in 234 patients with refractory epilepsy having acute repetitive seizures showed diazepam AI was significantly more effective than placebo AI at delaying the next seizure or rescue
Abou-Khalil B et al. A double-blind, randomized, placebo-controlled trial of a diazepam autoinjector administered by caregivers to patients with epilepsy who require intermittent intervention for acute repetitive seizures. Epilepsia. 2013 Nov ; 54(11): 1968-76
New applications of existing drugs
LevetiracetamApproved for focal seizure and juvenile myoclonic epilepsy
Generalized tonic clonic seizures
Status epilepticus
Phase III
Rufinamide• Approved as adjunctive treatment of seizures associated with LGS
syndrome in children > 4 years
• Currently Phase III trial is ongoing to evaluate Rufinamide in paediatric subjects 1-4 years of age
Lacosamide
Approved as adjunctive therapy in the treatment of partial-onset seizures in patients > 17 years
• Phase IV completed in August 2013-positive result
Monotherapy for patients with partial-
onset seizures
• Phase II, open-label trial- OngoingAdjunctive therapy in paediatric population(1 month – 17 years of
age)
• Phase II, open-label trial-Completed in august 2011 with significant results
Adjunctive therapy in primary generalized tonic-clonic seizures
Conclusions :
Epilepsy is a treatable disorder, goal of treatment should be “no
seizures and least side-effects”.
Although current AEDs are helpful, serious unmet needs
continue to exist with regards to disease modifications
However now there are promising treatments in early and later
stages of clinical development.