Clinical Trial Results:
A Double-Blind, Placebo-Controlled, Parallel-Group Study of Rufinamide Given as Adjunctive Therapy in Patients with Refractory Partial Seizures
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Summary
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EudraCT number |
2016-004944-12 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
20 May 2009
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Results information
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Results version number |
v2(current) |
This version publication date |
03 Jul 2019
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First version publication date |
18 May 2019
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
E2080-A001-301
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00334958 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Eisai Inc.
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Sponsor organisation address |
155 Tice Boulevard, Woodcliff Lake, United States,
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Public contact |
Eisai Medical Information, Eisai Inc., 1 8882472378, esi_oncmedinfo@eisai.com
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Scientific contact |
Eisai Medical Information, Eisai Inc., 1 8882472378, esi_oncmedinfo@eisai.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 May 2009
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
20 May 2009
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the effect of rufinamide on total partial seizure frequency in adolescent and adult participants (12 to 80 years, inclusive) with refractory partial onset seizures maintained on a maximum of 3 stable antiepileptic drugs (AEDs).
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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
- Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312
- European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 Feb 2006
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 343
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Country: Number of subjects enrolled |
Canada: 13
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Worldwide total number of subjects |
356
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
36
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Adults (18-64 years) |
308
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Participants were screened at 75 centers (69 in the United States and 6 in Canada). Participants were enrolled at 65 centers (61 in the United States and 4 in Canada). | ||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Carer | ||||||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Rufinamide | ||||||||||||||||||||||||||||||
Arm description |
For the 12-day Titration Phase, rufinamide was administered orally in doses starting with 400 mg twice daily and increased every 3 days in 400 mg twice daily increments up to 1600 mg twice daily (total daily dose 3200 mg). For the Maintenance Phase, maintenance doses of 1600 mg twice daily (3200 mg total daily dose) were administered. Subjects unable to tolerate the target dose (3200 mg/day) were allowed only during the Titration Phase to have the dose reduced to 3 tablets twice daily (corresponding to a dose of 2400 mg/day in the rufinamide group). | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Rufinamide
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Investigational medicinal product code |
E2080
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Other name |
BANZEL
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Rufinamide was administered orally in doses starting with 400 mg twice daily and increased every 3 days in 400 mg twice daily increments up to 1600 mg twice daily (total daily dose 3200 mg). For the Maintenance Phase, maintenance doses of 1600 mg twice daily (3200 mg total daily dose) were administered. Subjects unable to tolerate the target dose (3200 mg/day) were allowed only during the Titration Phase to have the dose reduced to 3 tablets twice daily (corresponding to a dose of 2400 mg/day in the rufinamide group).
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm description |
For the 12-day Titration Phase and the Maintenance Phase, rufinamide matching-placebo orally, twice daily was administered. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Rufinamide matching placebo was administered orally, twice daily.
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Baseline characteristics reporting groups
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Reporting group title |
Rufinamide
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Reporting group description |
For the 12-day Titration Phase, rufinamide was administered orally in doses starting with 400 mg twice daily and increased every 3 days in 400 mg twice daily increments up to 1600 mg twice daily (total daily dose 3200 mg). For the Maintenance Phase, maintenance doses of 1600 mg twice daily (3200 mg total daily dose) were administered. Subjects unable to tolerate the target dose (3200 mg/day) were allowed only during the Titration Phase to have the dose reduced to 3 tablets twice daily (corresponding to a dose of 2400 mg/day in the rufinamide group). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
For the 12-day Titration Phase and the Maintenance Phase, rufinamide matching-placebo orally, twice daily was administered. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rufinamide
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Reporting group description |
For the 12-day Titration Phase, rufinamide was administered orally in doses starting with 400 mg twice daily and increased every 3 days in 400 mg twice daily increments up to 1600 mg twice daily (total daily dose 3200 mg). For the Maintenance Phase, maintenance doses of 1600 mg twice daily (3200 mg total daily dose) were administered. Subjects unable to tolerate the target dose (3200 mg/day) were allowed only during the Titration Phase to have the dose reduced to 3 tablets twice daily (corresponding to a dose of 2400 mg/day in the rufinamide group). | ||
Reporting group title |
Placebo
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Reporting group description |
For the 12-day Titration Phase and the Maintenance Phase, rufinamide matching-placebo orally, twice daily was administered. | ||
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End point title |
Percentage change in Total Partial Seizure Frequency per 28 Days During Maintenance Phase Relative to the Baseline Phase [1] | ||||||||||||
End point description |
Seizure data was collected via patient diary, which was used to record daily seizure count and type. Intent-to-treat (ITT) population: All randomized subjects who had baseline Patient Seizure Diary data and had at least completed the titration period.
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End point type |
Primary
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End point timeframe |
Baseline, Days 13 to 96
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| 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 data was planned to be analyzed for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants with 50% or Greater Reduction in Total Partial Seizure Frequency per 28 Days During the Maintenance Phase Relative to the Baseline Phase | ||||||||||||
End point description |
Seizure data was collected via patient diary, which was used to record daily seizure count and type. ITT population: All randomized subjects who had baseline Patient Seizure Diary data and had at least completed the titration period.
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End point type |
Secondary
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End point timeframe |
Baseline, Days 13 to 96
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Log10 Transformed Total Partial Seizure Frequency per 28 Days during the Baseline Phase and Maintenance Phase | ||||||||||||
End point description |
Total partial seizure frequencies per 28 days during the double-blind Maintenance and Baseline Phases were transformed using logarithms to the base 10 (log10), because it was expected from previous studies that the results would not be normally distributed. ITT population: All randomized subjects who had baseline Patient Seizure Diary data and had at least completed the titration period.
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End point type |
Secondary
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End point timeframe |
Days 13 to 96
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Reduction from Baseline in Total Partial Seizure Frequency Rate (RRATIO) during Maintenance Phase | ||||||||||||
End point description |
RRATIO= 100*(T-B)/(T+B) where T= total seizure frequency per 28 days during the Maintenance Phase, and B=total seizure frequency per 28 days during the Baseline Phase. ITT population: All randomized subjects who had baseline Patient Seizure Diary data and had at least completed the titration period.
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End point type |
Secondary
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End point timeframe |
Baseline, Days 13 to 96
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All serious AEs (SAEs) were collected throughout the study from the time of consent to follow-up visit or 30 days after study drug discontinuation, whichever was longer. Serious adverse events (SAEs), regardless of causality assessment, were collected thr
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.0
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Reporting groups
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Reporting group title |
Rufinamide
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Reporting group description |
For the 12-day Titration Phase, rufinamide was administered orally in doses starting with 400 mg twice daily and increased every 3 days in 400 mg twice daily increments up to 1600 mg twice daily (total daily dose 3200 mg). For the Maintenance Phase, maintenance doses of 1600 mg twice daily (3200 mg total daily dose) were administered. Subjects unable to tolerate the target dose (3200 mg/day) were allowed only during the Titration Phase to have the dose reduced to 3 tablets twice daily (corresponding to a dose of 2400 mg/day in the rufinamide group). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
For the 12-day Titration Phase and the Maintenance Phase, rufinamide matching-placebo orally, twice daily was administered. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
