Focal Epilepsy Clinical Trial
Official title:
Post-market Study of AMPA Receptor Antagonists for Epilepsy Patients in Hong Kong
Background:
Epilepsy is a chronic neurological disease which affects approximately 70,000 patients in
Hong Kong and 50 billion people worldwide. Among these patients one-third remained
unresponsive to antiepileptic agents. Continual drug manipulation is an essential therapeutic
option for these patients with refractory epilepsy. In particular, rational polytherapy has
become the mainstay of treatment for the sub-group of patients who have failed two or more
antiepileptic drugs (AEDs).
A substantial amount of research has shown that N-methyl-D-aspartate receptors (NMDA) may
play a key role in the pathophysiology of several neurological diseases, including epilepsy.
Animal models of epilepsy and clinical studies demonstrate that NMDA receptors activity and
expression can be altered in association with epilepsy and particularly in some specific
seizure types. NMDA receptor antagonists have been shown to have antiepileptic effects in
both clinical and preclinical studies. There is some evidence that conventional antiepileptic
drugs may also affect NMDA receptor function.
Aims:
To investigate the medium to long-term effects of AMPA/NMDA receptor antagonist in an Asian
cohort as there is a relative lack of clinical data in this population To explore the
efficacy of AMPA/NMDA receptor antagonist in patients with partial onsets seizures that may
secondarily generalize and the specific side effects of AMPA/NMDA receptor antagonist in
relation to behavioral problems.
Methods:
A semi-prospective design is adopted to recruit patients who are indicated and started on
AMPA/NMDA receptor antagonist aged 12 or above in Hong Kong. This study will collect
information about demographic details, medical history and seizure information. Assessment of
seizure frequency is based on seizure diary and interviews with family members. Physical
examination, electrocardiogram and other medical information relevant to the follow-up of the
patient will be collected.
Epilepsy is a chronic neurological disease which affects approximately 70,000 patients in
Hong Kong and 50 billion people worldwide. Among these patients, one-third remained
unresponsive to antiepileptic agents. Continual drug manipulation is an essential therapeutic
option for these patients with refractory epilepsy. In particular, rational polytherapy has
become the mainstay of treatment for the sub-group of patients who have failed two or more
antiepileptic drugs (AEDs).
Using AEDs with different mechanisms of action is a strategy adopted by many doctors around
the world. In this regard, perampanel (PER) is an agent which is first in its class, with
specific antagonistic action on ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic
acid (AMPA) glutamate receptor of post-synaptic neurons. The pharmacokinetics of PER
suggested that it has a half-life of approximately 105 hours and the steady-state
concentrations that can be reached in 14 days. PER is approximately 95% bound to plasma
proteins. This metabolism is mediated by CYP 3A4 or CYP 3A5. The usual dosage of PER is
between 2mg and 12 mg. PER can be administered once daily.
A total of five clinical studies demonstrated the efficacy of PER among patients with
refractory epilepsy. These were all double-blind studies and all of them evaluated the 50%
responder rate as a seizure outcome. The corresponding risk ratio for 50% responder rates for
4mg, 8mg and 12mg were 1.54, 1.8 and 1.72. The most common treatment-emergent adverse effects
were dizziness, drowsiness, headache, fatigue, nasopharyngitis. The pooled results suggested
that a higher dose was more efficacious if the side effects could be tolerated. There was an
on-going study on the use of PER among patients with secondarily generalized seizures.
Perampanel has been approved in many countries such as USA, EU, Australia, Canada,
Switzerland, Singapore, and Malaysia, as an adjunctive therapy for refractory partial
seizures with or without secondary generalisation among patients above 12 years of age.
A substantial amount of research has shown that N-methyl-D-aspartate receptors (NMDA) may
play a key role in the pathophysiology of several neurological diseases, including epilepsy.
Animal models of epilepsy and clinical studies demonstrate that NMDA receptors activity and
expression can be altered in association with epilepsy and particularly in some specific
seizure types. NMDA receptor antagonists have been shown to have antiepileptic effects in
both clinical and preclinical studies. There is some evidence that conventional antiepileptic
drugs may also affect NMDA receptor function.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT02245061 -
Cortical Excitability Assessment Using Paired Pulses
|
N/A | |
Terminated |
NCT05081518 -
A Study of Lu AG06466 in Participants With Treatment Resistant Focal Epilepsy
|
Phase 1 | |
Withdrawn |
NCT05481905 -
ENACT: A Study of ENX-101 as Adjunctive Treatment in Patients With Focal Seizures
|
Phase 2 | |
Completed |
NCT02208492 -
The Effects on Cognitive Function of Levetiracetam (Keppra®) Compared to Carbamazepine (Tegretol®, Carmazepine®) as Monotherapy for Children With Partial Seizure; A Multicentric Randomized Controlled Study
|
Phase 4 | |
Recruiting |
NCT04839601 -
RNS System RESPONSE Study
|
N/A | |
Completed |
NCT02898935 -
Improvement of the Accuracy of Spatial Representation of Invasive Exploratory Electrodes in Focal Epilepsy
|
||
Enrolling by invitation |
NCT05748236 -
The Efficacy and Safety of Lamotrigine Versus Carbamazepine in Focal Epilepsy
|
Phase 4 | |
Terminated |
NCT01724918 -
Lacosamide IV and EEG/EKG (LIVE) Study
|
Phase 2 | |
Completed |
NCT00855738 -
A Prospective, Observational Study On The Effectiveness Of New Antiepileptic Drugs As First Bitherapy In The Daily Clinical Practice
|
Phase 4 | |
Recruiting |
NCT06309966 -
Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy
|
Phase 2/Phase 3 | |
Not yet recruiting |
NCT06210022 -
Cognitive Impairment in Drug-resistant and Drug-responsive Focal Cryptogenic Epilepsy
|
||
Completed |
NCT01311440 -
Modified Atkins Diet Treatment for Adults With Drug-resistant Epilepsy
|
N/A | |
Terminated |
NCT03955432 -
Long-term Cardiac Monitoring in Epilepsy
|
N/A | |
Recruiting |
NCT06132893 -
A Study to Determine if BHV-7000 is Effective and Safe in Adults With Refractory Focal Onset Epilepsy
|
Phase 2/Phase 3 | |
Recruiting |
NCT05100771 -
Optimized Volumetry in Radiology: Interest in Pediatric Brain MRI in the Exploration of Focal Epilepsy
|
||
Recruiting |
NCT04879433 -
Prospective Open-label Evaluation of Cenobamate Adjunctive Treatment of Adults With Refractory Focal Epilepsy
|
||
Active, not recruiting |
NCT03916848 -
Novel Network Analysis of Intracranial Stereoelectroencephalography
|
N/A | |
Recruiting |
NCT05198882 -
Clinical Evaluation of Interstitial Laser Thermal Therapy Under Continuous MRI Monitoring as a Minimally Invasive Treatment of Patients With Medically Unbalanced Partial Epilepsy
|
Phase 1 | |
Recruiting |
NCT05981755 -
Breathing Rescue for SUDEP Prevention
|
N/A | |
Not yet recruiting |
NCT06443463 -
Long-term Safety and Tolerability of BHV-7000
|
Phase 2 |