Clinical Trial Results:
Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Perampanel as Monotherapy or First Adjunctive Therapy in Subjects With Partial Onset Seizures With or Without Secondarily Generalized Seizures or With Primary Generalized Tonic-Clonic Seizures
|
Summary
|
|
EudraCT number |
2017-001180-20 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
27 Apr 2021
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
13 Nov 2021
|
First version publication date |
13 Nov 2021
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
E2007-G000-410
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT03288129 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Eisai Inc.
|
||
Sponsor organisation address |
100 Tice Boulevard, Woodcliff Lake, New Jersey, United States, 07677
|
||
Public contact |
Eisai Medical Information, Eisai Inc., 1 888-274-2378, esi_medinfo@eisai.com
|
||
Scientific contact |
Eisai Medical Information, Eisai Inc., 1 888-274-2378, esi_medinfo@eisai.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
27 Apr 2021
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
27 Apr 2021
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The primary objective of this study was to assess the retention rate of perampanel when
given as monotherapy or 1st adjunctive therapy in subjects with partial-onset seizures (POS)
or primary generalized tonic clonic seizures (PGTCS).
|
||
Protection of trial subjects |
This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Aug 2017
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United States: 54
|
||
Worldwide total number of subjects |
54
|
||
EEA total number of subjects |
0
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
4
|
||
Adults (18-64 years) |
44
|
||
From 65 to 84 years |
6
|
||
85 years and over |
0
|
||
|
|||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||
Recruitment details |
Subjects took part in the study at 14 investigative sites in the United States from 23 August 2017 to 27 April 2021. | ||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||
Screening details |
A total of 68 subjects were screened, of which 55 were enrolled and 54 were treated with perampanel. The study consisted of 4 periods: Screening Period (to start no earlier than 6 weeks before the 1st dose of study drug), Titration Period (up to 13 weeks), Maintenance Period (39 weeks), and Follow up Period (4 weeks). | ||||||||||||||||||
|
Period 1
|
|||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
|
||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||
|
Arms
|
|||||||||||||||||||
|
Arm title
|
Perampanel | ||||||||||||||||||
Arm description |
The study treatment phase consisted of a Titration Period (up to 13 weeks) and a Maintenance Period (39 weeks) for up to a total of 52 weeks. Each subject received oral perampanel once daily at bedtime. During the Titration Period, the starting daily dose was 2 milligram (mg) for 2 weeks, then titrated to 4 mg for 2 weeks. Thereafter, further dose titrations in increments of 2 mg up to 12 mg were allowed based on the subject's response and tolerability and at the investigator's judgement. During the Maintenance Period, subjects continued to receive the perampanel dose level that was administered at the end of the Titration Period. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Perampanel
|
||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||
Other name |
Fycompa, E2007
|
||||||||||||||||||
Pharmaceutical forms |
Film-coated tablet
|
||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||
Dosage and administration details |
Subjects received oral perampanel once daily at bedtime. During the Titration Period, the starting daily dose was 2 mg for 2 weeks, then titrated to 4 mg for 2 weeks. Thereafter, further dose titrations in increments of 2 mg up to 12 mg were allowed based on the subject's response and tolerability and at the investigator's judgement. During the Maintenance Period, subjects continued to receive the perampanel dose level that was administered at the end of the Titration Period.
|
||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Perampanel
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The study treatment phase consisted of a Titration Period (up to 13 weeks) and a Maintenance Period (39 weeks) for up to a total of 52 weeks. Each subject received oral perampanel once daily at bedtime. During the Titration Period, the starting daily dose was 2 milligram (mg) for 2 weeks, then titrated to 4 mg for 2 weeks. Thereafter, further dose titrations in increments of 2 mg up to 12 mg were allowed based on the subject's response and tolerability and at the investigator's judgement. During the Maintenance Period, subjects continued to receive the perampanel dose level that was administered at the end of the Titration Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Perampanel
|
||
Reporting group description |
The study treatment phase consisted of a Titration Period (up to 13 weeks) and a Maintenance Period (39 weeks) for up to a total of 52 weeks. Each subject received oral perampanel once daily at bedtime. During the Titration Period, the starting daily dose was 2 milligram (mg) for 2 weeks, then titrated to 4 mg for 2 weeks. Thereafter, further dose titrations in increments of 2 mg up to 12 mg were allowed based on the subject's response and tolerability and at the investigator's judgement. During the Maintenance Period, subjects continued to receive the perampanel dose level that was administered at the end of the Titration Period. | ||
|
|||||||||
End point title |
Percentage of Subjects Remaining on Perampanel Treatment at 3 months After the Initiation of Treatment [1] | ||||||||
End point description |
The retention rate was defined as the percentage of subjects remaining on perampanel treatment at 3 months after the initiation of treatment. The Safety Analysis Set included subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Month 3
|
||||||||
| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics data was planned to be analyzed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects Remaining on Perampanel Treatment at 6 months After the Initiation of Treatment [2] | ||||||||
End point description |
The retention rate was defined as the percentage of subjects remaining on perampanel treatment at 6 months after the initiation of treatment. The Safety Analysis Set included subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Month 6
|
||||||||
| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics data was planned to be analyzed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects Remaining on Perampanel Treatment at 12 months After the Initiation of Treatment [3] | ||||||||
End point description |
The retention rate was defined as the percentage of subjects remaining on perampanel treatment at 12 months after the initiation of treatment. The Safety Analysis Set included subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Month 12
|
||||||||
| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics data was planned to be analyzed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects Remaining on Perampanel Treatment at 9 months After the Initiation of Treatment [4] | ||||||||
End point description |
The retention rate was defined as the percentage of subjects remaining on perampanel treatment at 9 months after the initiation of treatment. The Safety Analysis Set included subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Month 9
|
||||||||
| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive statistics data was planned to be analyzed for this endpoint. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects who Achieved Seizure-free Status During the Maintenance Period | ||||||||
End point description |
Seizure-free status was defined as no incidence of seizure during the entire maintenance period. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: subject does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: subject loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately. The Full Analysis Set (FAS) included subjects who received at least 1 dose of study drug and had at least 1 postdose seizure measurement. Here “number analyzed” were subjects who were evaluable for the outcome measure at given time points.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 39 weeks in Maintenance Period
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects who Achieved 3-month Seizure-free Status | ||||||||
End point description |
Seizure-free status was defined as no incidence of seizure at 3 months. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: subject does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: subject loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately. The FAS included subjects who received at least 1 dose of study drug and had at least 1 postdose seizure measurement. Here “number analyzed” were subjects who were evaluable for the outcome measure at given time points.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to Month 3 in Maintenance Period
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects who Achieved 6-month Seizure-free Status | ||||||||
End point description |
Seizure-free status was defined as no incidence of seizure at 6 months. Partial seizures: when abnormal electrical activity begins in only one part of brain include (1) simple partial seizures: subject does not lose consciousness may experience muscle jerking or stiffening, (2) complex partial seizures: subject loses awareness. SGS: disturbances that spread to both sides of brain after partial seizure has already begun and happen when burst of electrical activity in limited area (the partial seizure) spreads throughout brain. PGTCS: disturbances in functioning of both sides of brain that caused by electrical signals spreading through brain inappropriately. The FAS included subjects who received at least 1 dose of study drug and had at least 1 postdose seizure measurement. Here “number analyzed” were subjects who were evaluable for the outcome measure at given time points.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to Month 6 in Maintenance Period
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Percentage of Subjects who Receive Perampanel as a First Adjunctive Therapy and Converted to Perampanel Monotherapy | ||||||||
End point description |
The number of subjects who receive perampanel as a first adjunctive therapy who were able to convert to perampanel monotherapy were reported. The FAS included subjects who received at least 1 dose of study drug and had at least 1 postdose seizure measurement. Here “number analyzed” were subjects who were evaluable for the outcome measure at given time points.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Up to 39 weeks
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||
End point title |
Number of Subjects With Treatment-emergent Adverse Events (TEAE) | ||||||
End point description |
A treatment-emergent AE (TEAE) was defined as an AE that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. The Safety Analysis Set included subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
From date of first administration of study drug up to 28 days after last dose of study drug up to approximately 56 weeks
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||
End point title |
Number of Subjects With Treatment-emergent Serious Adverse Events (SAE) | ||||||
End point description |
A SAE was defined as any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect. A treatment-emergent AE was defined as an event that emerges during treatment having been absent pre-treatment, or worsens relative to the pre-treatment state. The Safety Analysis Set included subjects who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
From date of first administration of study drug up to 28 days after last dose of study drug up to approximately 56 weeks
|
||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From date of first administration of study drug up to 28 days after last dose of study drug up to approximately 56 weeks
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Perampanel
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
The study treatment phase consisted of a Titration Period (up to 13 weeks) and a Maintenance Period (39 weeks) for up to a total of 52 weeks. Each subject received oral perampanel once daily at bedtime. During the Titration Period, the starting daily dose was 2 mg for 2 weeks, then titrated to 4 mg for 2 weeks. Thereafter, further dose titrations in increments of 2 mg up to 12 mg were allowed based on the subject's response and tolerability and at the investigator's judgement. During the Maintenance Period, subjects continued to receive the perampanel dose level that was administered at the end of the Titration Period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
12 Apr 2019 |
Amendment 01: Added number and location of study sites, and the number of subjects. Screening Period seizure requirements, the length of Titration Period were clarified. Updated minimum age for study inclusion. The requirements to support epilepsy diagnosis and analysis of efficacy endpoints were clarified. Updated exclusion criteria regarding concomitant therapies and procedures. Updated subject treatment during the follow-Up Period. Added fasting laboratory assessments at screening and last treatment visit. Updated Medical Monitor and Study
Director information. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
