Clinical trial NCT03457129
Conditions: Epilepsy
Keywords: Epilepsy Epilepsy, partial onset Epilepsy, generalized onset Fycompa perampanel
Sponsor: University of Arizona
Start date: 2018-04-18; Completion date: 2021-12-15
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will aim to improve retention and tolerability by slowing the initial titration rate of perampanel from a standard up-titration rate of 2 week intervals to a slower up-titration rate consisting of 3 week intervals. Subjects will be randomized to either perampanel, standard titration interval rate (Group A) or perampanel, slower titration interval rate (Group B).

Detailed description:
A total of 60 subjects with a confirmed diagnosis of either partial onset or primary generalized epilepsy will be recruited into the trial. 30 subjects will initiate perampanel at a dose of 2 mg/day and titrate upwards every 2 weeks to a target dose of 6 mg/day. Subjects in this group will be designated Group A. The remaining 30 subjects will also begin perampanel at a dose of 2 mg/day but will titrate upwards every 3 weeks to a target dose of 6 mg/day and will be designated Group B.

Arms: arm 1: Perampanel oral tablet: 2mg by mouth every 24 hours for two weeks, then up-titrated by 2 mg every two weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control. arm 2: Perampanel oral tablet: 2mg by mouth every 24 hours for three weeks, then up-titrated by 2 mg every three weeks to a target dose of 6 mg/day. Minimum total daily dose = 2 mg/day. Maximum daily dose is 12 mg/day. Total daily dose will be determined by the Investigator based on tolerability and seizure control.
Interventions: intervention 1: Perampanel Oral Tablet
Intervention descriptions: intervention 1: Perampanel is an AMPA receptor blockade, that has shown to be efficacious for seizure reduction in both partial onset seizures and generalized tonic-clonic seizures. Perampanel was approved by the FDA in October 2012 as adjunctive treatment in patients with partial onset seizures. Additionally, in June 2015, Fycompa was approved as adjunctive therapy in patients with primary generalized tonic clonic seizures.

Protocol documents:
Prot_SAP_000.pdf: 
 
Fycompa titration intervals and effects on retention rates 
 
 
NCT03457129 
 
 
Date of Document: 10/15/2021 
Document Type: Study Protocol 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IIS PROTOCOL SYNOPSIS 
 


 
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Protocol Title:  
Fycompa titration intervals and effects on retention rates 
 
Principal Investigator 
Name: 
Norman Wang, MD 
 
Principal Investigator 
Contact Information: 
755 E McDowell Rd, 3rd floor.  Phoenix, AZ 85006 
phone (602)-521-3233   fax (602)-521-3016  
Norman.Wang@Bannerhealth.com 
Institution Name(s): 
Banner University Medicine Neuroscience Institute  
Sub-Investigator Name, if 
applicable: 
Steve Chung, MD 
Hussam Seif-Eddeine, MD 
Do you plan on using other 
Institutions or centers to 
conduct study?   
If yes, please list name(s) 
and address(es): 
 YES          
 NO 
 
 
N/A 
 
Rationale: 
With its novel mechanism of AMPA receptor blockade, Fycompa is efficacious 
for seizure reduction in both partial onset seizures and generalized tonic-clonic 
seizures. As only a few of antiepileptic medications have this capability, it is 
important to elucidate the ideal methods of avoiding complications and 
improving retention rates.   
Recent studies find real-world rates currently range from 44-89% (Trinka et al 
2016).  Personal clinical experience has revealed difficulty in maintaining 
patients on Fycompa due to adverse effects.  However, certain studies find 
correlations between slower titration schedules and lower side effect 
percentages (Trinka et al 2016, Lawthom et al, 2014).   
We therefore propose to test whether a slower initial upward titration (2mg 
increase every 3 weeks) improves 1-year retention rates as compared to those of 
a more typical titration every 2 weeks.   As any retention rate may be affected 
by adverse effects and/or seizure frequency, these will be followed as secondary 
endpoints. 
Study Design:  
 
 
 
 
 
 
 
 
 
 
A total of 60 patients with a confirmed diagnosis of either partial onset or 
primary generalized epilepsy will be recruited into the trial. 30 patients will 
initiate Fycompa at a dose of 2 mg/day and titrate upward every 2 weeks to a 
target dose of 6 mg/day. Patients in this group will be designated Group A. The 
remaining 30 patients will also begin Fycompa at a dose of 2 mg/day but will 
titrate upwards every 3 weeks to a target dose of 6 mg/day and will be 
designated Group B. Initial study visits will occur every two weeks for the first 
2 months in order to assess for titration related adverse effects. Long term 
evaluation of retention rates will be calculated at 3, 6, 9 and 12 months after 
enrollment.  


 
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Objectives:  
Primary:  
To evaluate the differences in retention rate between patients using a more 
conventional upward titration schedule (Group A) vs. those using a 
slower up-titration schedule (Group B). 
Secondary:  
1. 
To compare the adverse effects reported in patients up-titrating 
Fycompa at a slower titration rate (Group B) to those titrating at a 
more conventional rate (Group A). 
2. To evaluate the short term and long term efficacy of perampanel 
between the two treatment groups. 
Subjects and Centers: 
A total of 60 epilepsy patients will be recruited from the Epilepsy Center at 
Banner University Medicine Neuroscience Institute. 30 patients will be 
randomly assigned to treatment group A, up-titrating Fycompa every 2 weeks 
while the remaining 30 being assigned to group B, up-titrating Fycompa every 3 
weeks.  
Inclusion Criteria:  
1. Must provide written informed consent signed by the subject or legal 
guardian prior to entering the study in accordance with the ICH, GCP 
guidelines if the written informed consent is provided by the legal guardian 
because the subject is unable to do so, a written or verbal assent from the 
subject must also be obtained. 
2. Subject has a confirmed diagnosis of medically refractory epilepsy with or 
without secondary generalization for at least 12 months prior to visit 1.  
3. Subjects currently being treated with 1 to 3 antiepileptic medications with 
or without VNS (does not count as an AED). 
4. Subjects aged 18 to 75. 
5. Subject’s requiring an additional epilepsy medication due to either 
uncontrolled seizure and/or lack of tolerability with current epilepsy 
medications 
6. Can be safely treated, in the opinion of the investigator with Fycompa. 
7. Able and agrees to follow specified titration schedule 
8. Subjects or a legal guardian who is able to communicate effectively with 
study personnel and considered reliable, able, willing and cooperative with 
regard to complying with protocol-defined requirements, including 
completion of the study diary. 


 
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Exclusion Criteria: 
1. Any history of non-epileptic or psychogenic 
seizures. 
2. Women who are currently pregnant, lactating or 
have plans to become pregnant in the immediate 
future. 
3. Subjects with active suicidal ideation or behavior 
as evidenced by positive answers on the Columbia 
Suicide Severity Rating Scale (C-SSRS) or 
subject’s with a history of suicidal ideation or 
attempt within 12 months. 
4. Subjects with a suicidal attempt in the 12 months 
prior to Visit 1 
5. Any clinically significant medical or psychiatric 
illness, psychological or behavioral problems, 
which in the opinion of the investigator would 
interfere with the subject’s ability to participate in 
the study.  
6. Subjects with severe hepatic impairment or severe 
renal impairment or on hemodialysis.  
7. Any use of concomitant medication as listed in the drug insert, 
including medications known to be inducers of cytochrome P450 
(CYP3A). 


 
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IIS PROTOCOL SYNOPSIS 
 
Other Therapy:  
Concomitant antiepileptic and medical treatment will be allowed as deemed 
necessary by the Principle investigator and/or sub-investigators. . 
Efficacy Measures:  
Patient diaries containing seizure types and frequencies along with adverse 
effects experienced will be maintained.  Seizure diaries will be reviewed in 
Epilepsy Clinic during study visits occurring at the following intervals: weeks 
0, 2, 4, 6, 8 then months 3, 6, 9, and 12.  Data point collation at study visits will 
include: 
  1. Fycompa dose taken and duration at this dose 
  2. Adverse effects experienced 
  3. Alterations to Fycompa dose once in maintenance phase. 
  4. Interim seizure types and number of each 
  5. Interim changes in other medication during maintenance phase.   
Safety Measures: 
Adverse effects and seizure frequency will be assessed at each clinic visit along 
with vital sign measurements and brief neurological exams.  Dosage 
adjustments of the Fycompa and other concomitant medications will be done at 
the discretion of the Investigator during the maintenance phase. 
Correlative Science: 
Data collected will be based on the patient’s seizure/adverse effect diary as well 
as patient/caregiver reports at each study visit. 
Statistical Analysis: 
The study will target a total size of 60 patients (30 per group).  This sample size 
will allow for a power of 0.85 to determine significant difference of 30% 
retention in group A and 70% retention in group B.   
Primary endpoint will be Fycompa retention rate at the end of 1 year with 
Kaplan-Meier survival curves created for both groups.  Log rank testing will be 
done to determine significant difference (p<0.05). Cox proportional hazard test 
will be done to quantify the odds of retention in each arm. 
Secondary endpoint analysis will be done to tabulated side effects experienced 
in each group and the percentages of patients reporting the effects. Seizure 
frequency per 28 days during initial titration and final maintenance will be 
calculated for each group.  Comparison within groups will be made by 
ANOVA. 
Data Collection: 
Data will be collected at each study visit through patient interview and the use 
of a seizure/adverse effect diary. 


 
Versi o n 1 1/ 0 3/ 2 0 1 7  
 
St u d y Dr u g Re gi me ns:  
Gr o u p A will ha ve F yc o m pa 2 m g q D f or 2 wee ks, t he n 4 m g q D f or 2 wee ks, 
t he n 6 m g q D f or at least 2 wee ks.  F urt her a dj ust me nts u p war d or d o w n war d i n 
t he mai nte na nce p hase will be all o we d as per I n vesti gat or’s discreti o n . We 
a ntici pate 1 5 will c o nti n ue at 6 m g, 8 will decrease t o 4 m g, a n d 7 will i ncrease 
t o 8 m g d uri n g t he ne xt 4 6 wee ks of mai nte na nce . 
Gr o u p B will ha ve F yc o m pa 2 m g q D f or 3 wee ks, t he n 4 m g q D  f or 3 wee ks, 
t he n 6 m g q D f or at least 3 wee ks.  F urt her a dj ust me nts u p war d or d o w n war d i n 
t he mai nte na nce p hase will be all o we d as per t he I n vesti gat or’s discreti o n . We 
a ntici pate 1 5 will c o nti n ue at 6 m g, 8 will decrease t o 4 m g, a n d 7 will i ncr ease 
t o 8 m g f or the re mai ni n g 4 0  wee ks of mai nte na nce .  
St u d y Dr u g Re q ueste d Per 
P atie nt:  
T O T A L: 2 m g ta blets = 1 1, 5 5 0   
               4 m g ta blets = 2 4, 7 9 4  
 
 
Are Cli nic al/ Dr u g S u p plies Re q u este d ? ( c hec k o nl y 1 b o x ): 
 ‘ Y E S’   
 ‘ N O’         
 
 
 
 
 
 
 
 
 
 
 
T ot al st u d y dr u g a m o u nt i n u nits (t a blets, c a ps ules, vi als, etc.):  
 
 
T ot al Acti ve Dr u g  
3 6, 3 4 4  t a blets 
 
 
A m o u nt of P ure S u bst a nce 
(if a p plic a ble) 
 
 


 
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IIS PROTOCOL SYNOPSIS 
 
Estimated Study Start Date: 
February 1, 2017 
Estimated Length of 
Enrollment: 
2 years 
Description of Site 
Enrollment Capabilities: 
The Banner University Medicine Neuroscience Institute, Epilepsy Center 
includes 3 full-time epileptologists, each with weekly outpatient clinics for 
epilepsy patients.  It also employs a full-time study coordinator. 
Estimated Study Duration: 
24 months from study initiation to data analysis and paper completion, allowing 
for a 12 month enrollment period. 
Potential written outcomes 
of this study (check all that 
apply): 
 Final Study Report          
 Submit for Presentation at scientific conference  
 
 Submit for Publication    
 Submit Abstract/Poster at scientific conference 
Publication Plan (if 
applicable): 
Epilepsia, submission in August 2020. 


 
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