Focal EpilepsyNCT03457961
Post-market Study of AMPA Receptor Antagonists for Epilepsy Patients in Hong Kong
An observational study of Focal Epilepsy and Generalized Epilepsy, run by Chinese University of Hong Kong at 1 site in Hong Kong.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Focal Epilepsy, Generalized Epilepsy, Partial Seizures, Simple
- What is being tested?
- Perampanel
- How many people
- 80 participants
- Where
- 1 siteHong Kong
- Study dates
- 23 Jul 2016to 1 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients (diagnosed epilepsy with simple partial seizure) who have a baseline seizure rate of more than 2 months would be provided perampanel as adjunctive treatment.
Who may be able to join
- Subject aged 12 years or above
- Subject has a diagnosis of epilepsy with simple partial seizure and/or complex partial seizures
- Subjects who have a baseline seizure rate of more than 2 per month in the eight week period preceding the start of AMPA / NMDA receptor antagonist
- No seizure free period longer than 21 days during the eight week period before AMPA receptor antagonist was started
- Patients who already had neuropsychiatric inventory completed twice during the treatment period spanning at least 16 weeks.
Who cannot join
- Subjects with idiopathic generalised epilepsy (for example, juvenile myoclonic epilepsy and absence epilepsy)
- Patients who only suffer from isolated auras
- Baseline creatinine clearance of less than 50ml/min
- Severe hepatic impairment with ALT three times the upper limits of normal
- Significant psychiatric conditions before the start of AMPA / NMDA receptor antagonist
- Progressive neurodegenerative conditions
Show all 11Show fewer
- Active history of malignancy
- History of severe haematological conditions or serious blood dyscrasias
- Corrected QT interval more than 450 milli-second on ECG
- Substance abuse
- Pregnancy, breastfeeding
Trial locations and contacts
1 site in 1 country.
Hong Kong1 site, 1 recruiting
- Recruiting
Prince of Wales Hospital
Hong Kong, 0000
Sau Man Celia Tse, +85257431802, saumanceliatse@cuhk.edu.hk
Ho Wan Leung
About this study
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).
Read more
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.
Read the detailed description
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.
- Being tested
- Perampanel
- Keywords
- Perampanel, focal onset seizure, epilepsy
- Medical subject headings
- Epilepsies, Partial, Epilepsy, Generalized, Seizures, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PerampanelDrug
Also called Fycompa
This study collects clinical information during the first 16 weeks after the first dose of AMPA/NMDA receptor antagonist. Subjects or caregivers shall provide seizure diary which documents seizure type and seizure frequency as per usual medical care. The final visit will be based on the week-16 visit.
| Study group | Role | What they receive |
|---|---|---|
| Adjunctive Perampanel | A group of patients who aged 12 years or above and have a diagnosis of epilepsy with simple partial seizure and/or complex partial seizures Receives: Drug: Perampanel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy end-points
The primary efficacy end-points evaluates seizure frequency (per month) in week 0 (baseline) and week 16 (maintenance phase). The investigators will used those seizure frequencies (per month) to calculate the percentage change from baseline to maintenance phase for each subject and categories: no change, between 0 to 50% decrease, 50% to 75% decrease, 75% to 100% decrease.
Measured: 16 weeks
Seizure freedom rate in study population
The proportion of subjects achieving seizure freedom during the maintenance period will be documented. The percentage of seizure free days in the maintenance phase will also be collected. The investigators will report the seizure freedom rate for the present study population and the average days of achieving seizure freedom.
Measured: 16 weeks
Secondary outcomes (1)
Psychiatric and behavioral adverse events
The investigators would use the Neuropsychiatric Inventory Questionnaire (NPI) with 12 domains to evaluate the neuropsychiatric events in week 0 (baseline) and week 16 (maintenance phase). The investigators will record each symptom severity (rated 1 occasional to 4 very frequent) and frequency (rated 1 mild to 3 severe).
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2018
- Study start23 Jul 2016
- Primary completion1 Jul 2021 (estimated)
- Study completion1 Jul 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Focal EpilepsyStudies of the same condition, open and under way.
- More trials run by Chinese University of Hong KongThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Howan Leung, Prince of Wales Hospital, Shatin, Hong Kong
- Investigators
- Ho Wan Leung, Principal investigator, Chinese University of Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03457961
- Sponsor's protocol ID
- 2016-HL-001
- Status last verified
- Aug 2020
- First submitted
- 25 Feb 2018
- Last updated
- 27 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: This is a cohort study for perampanel in Hong Kong. There is no plan to make individual participant data to share. The results would be shared in publications. Electronic data will be saved in secured computer of the individual sites with restricted access. The anonymous data will be managed installed for developing future studies.
Publications
Steinhoff BJ, Bacher M, Bast T, Kornmeier R, Kurth C, Scholly J, Staack AM, Wisniewski I. First clinical experiences with perampanel--the Kork experience in 74 patients. Epilepsia. 2014 Jan;55 Suppl 1:16-8. doi: 10.1111/epi.12492.
PubMed 24400693Juhl S, Rubboli G. Perampanel as add-on treatment in refractory focal epilepsy. The Dianalund experience. Acta Neurol Scand. 2016 Nov;134(5):374-377. doi: 10.1111/ane.12558. Epub 2016 Jan 13.
PubMed 26763771Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurol Scand. 2016 Mar;133(3):160-72. doi: 10.1111/ane.12529. Epub 2015 Oct 28.
PubMed 26506904
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-market Study of AMPA Receptor Antagonists for Epilepsy Patients in Hong Kong
- ClinicalTrials.gov ID
- NCT03457961
- Acronym / sponsor ID
- 2016-HL-001
- Keywords
- Perampanel, focal onset seizure, epilepsy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Chinese University of Hong KongUniversity, hospital or other
- Study start
- 23 Jul 2016 (actual)
- Primary completion
- 1 Jul 2021 (estimated)
- Study completion
- 1 Jul 2021 (estimated)
- First posted
- 8 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adjunctive Perampanel | – | Drug: PerampanelA group of patients who aged 12 years or above and have a diagnosis of epilepsy with simple partial seizure and/or complex partial seizures |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients (diagnosed epilepsy with simple partial seizure) who have a baseline seizure rate of more than 2 months would be provided perampanel as adjunctive treatment.
Key inclusion criteria (5 listed)
- Subject aged 12 years or above
- Subject has a diagnosis of epilepsy with simple partial seizure and/or complex partial seizures
- Subjects who have a baseline seizure rate of more than 2 per month in the eight week period preceding the start of AMPA / NMDA receptor antagonist
- No seizure free period longer than 21 days during the eight week period before AMPA receptor antagonist was started
- Patients who already had neuropsychiatric inventory completed twice during the treatment period spanning at least 16 weeks.
Key exclusion criteria (11 listed)
- Subjects with idiopathic generalised epilepsy (for example, juvenile myoclonic epilepsy and absence epilepsy)
- Patients who only suffer from isolated auras
- Baseline creatinine clearance of less than 50ml/min
- Severe hepatic impairment with ALT three times the upper limits of normal
- Significant psychiatric conditions before the start of AMPA / NMDA receptor antagonist
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PerampanelAlso: FycompaThis study collects clinical information during the first 16 weeks after the first dose of AMPA/NMDA receptor antagonist. Subjects or caregivers shall provide seizure diary which documents seizure type and seizure frequency as per usual medical care. The final visit will be based on the week-16 visit. | Drug | Adjunctive Perampanel |
Primary outcome
Efficacy end-points
Time frame: 16 weeks
The primary efficacy end-points evaluates seizure frequency (per month) in week 0 (baseline) and week 16 (maintenance phase). The investigators will used those seizure frequencies (per month) to calculate the percentage change from baseline to maintenance phase for each subject and categories: no change, between 0 to 50% decrease, 50% to 75% decrease, 75% to 100% decrease.
Seizure freedom rate in study population
Time frame: 16 weeks
The proportion of subjects achieving seizure freedom during the maintenance period will be documented. The percentage of seizure free days in the maintenance phase will also be collected. The investigators will report the seizure freedom rate for the present study population and the average days of achieving seizure freedom.
1 secondary outcome
Psychiatric and behavioral adverse events
Time frame: 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2020.
- Background: PubMed 24400693Steinhoff BJ, Bacher M, Bast T, Kornmeier R, Kurth C, Scholly J, Staack AM, Wisniewski I. First clinical experiences with perampanel--the Kork experience in 74 patients. Epilepsia. 2014 Jan;55 Suppl 1:16-8. doi: 10.1111/epi.12492.
- Background: PubMed 26763771Juhl S, Rubboli G. Perampanel as add-on treatment in refractory focal epilepsy. The Dianalund experience. Acta Neurol Scand. 2016 Nov;134(5):374-377. doi: 10.1111/ane.12558. Epub 2016 Jan 13.
- Background: PubMed 26506904Trinka E, Steinhoff BJ, Nikanorova M, Brodie MJ. Perampanel for focal epilepsy: insights from early clinical experience. Acta Neurol Scand. 2016 Mar;133(3):160-72. doi: 10.1111/ane.12529. Epub 2015 Oct 28.
- Individual participant dataSharing planned: No. This is a cohort study for perampanel in Hong Kong. There is no plan to make individual participant data to share. The results would be shared in publications. Electronic data will be saved in secured computer of the individual sites with restricted access. The anonymous data will be managed installed for developing future studies.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ho Wan Leung principal investigator
Chinese University of Hong Kong
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Focal Epilepsy and Generalized Epilepsy, run by Chinese University of Hong Kong at 1 site in Hong Kong.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Hong Kong. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sau Man Celia Tse (85257431802, saumanceliatse@cuhk.edu.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy end-points (time frame: 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03457961, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2020.