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Evaluation of the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures

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ClinicalTrials.gov Identifier: NCT00735397
Recruitment Status : Completed
First Posted : August 14, 2008
Results First Posted : January 26, 2016
Last Update Posted : March 14, 2016
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Tracking Information
First Submitted Date  ICMJE August 13, 2008
First Posted Date  ICMJE August 14, 2008
Results First Submitted Date  ICMJE September 16, 2015
Results First Posted Date  ICMJE January 26, 2016
Last Update Posted Date March 14, 2016
Study Start Date  ICMJE October 2008
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2015)
Number of Participants With Treatment-emergent Non-Serious Adverse Events (AEs) and Treatment-emergent Serious Adverse Events (SAEs) [ Time Frame: From date of first dose of perampanel up to 30 days after the last dose of perampanel or up to approximately 5 years. ]
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered with an investigational product. A SAE was defined as any untoward medical occurrence that at any dose; resulted in death, was life-threatening (ie, the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was as a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). In this study, treatment emergent AEs (defined as an AE (serious or non-serious) that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed.
Original Primary Outcome Measures  ICMJE
 (submitted: August 13, 2008)
Efficacy will be assessed by seizure counts (subject's diaries). [ Time Frame: Assessments are done every 4 wks during the first 16 wks w/interim telephone contacts between visits. After 16 wks, they will be done every 12 wks w/interim telephone contacts in between. Subjects maintain seizure diary cards throughout entire study. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2015)
  • Median Percent Change in Seizure Frequency Per 28 Days Relative to Pre-Perampanel Baseline. [ Time Frame: Pre-perampanel Baseline and Weeks (1-13, 14-26, 27-39, 40-52, 53-65, 66-78, 79-91, 92-104, 105-117, 118-130, 131-143, 144-156, 157-169, 170-182, 183-195, 196-208, 209-221, 222-234, 235-247, and 248-260) ]
    Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The seizure frequency per 28 days was calculated as the number of seizures divided by the number of days in the interval and multiplied by 28. The percent change in 28-day seizure frequency from pre-perampanel baseline was assessed for all partial-onset seizure types. The pre-perampanel baseline was defined as: (1) for participants who had been assigned to placebo treatment in the core DB study, the pre-perampanel baseline was computed from all data during the core DB study, and (2) for participants who had been assigned to perampanel in the core DB study, the pre-perampanel baseline was computed from the pre-randomization phase of the core DB study.
  • Percentage of Participants Who Experienced a 50% or Greater Reduction in Seizure Frequency Per 28 Days Relative to the Pre-Perampanel Baseline. [ Time Frame: Pre-perampanel Baseline and Weeks (1-13, 14-26, 27-39, 40-52, 53-65, 66-78, 79-91, 92-104, 105-117, 118-130, 131-143, 144-156, 157-169, 170-182, 183-195, 196-208, 209-221, 222-234, 235-247, 248-260) ]
    Seizure frequency was derived from information (seizure count and type) recorded in participant diary. The percentage of participants who experienced a 50% or greater reduction in seizure frequency per 28 days relative to the pre-perampanel Baseline(responders) was assessed. The pre-perampanel baseline was defined as: (1) for participants who had been assigned to placebo treatment in the core DB study, the Pre-perampanel baseline was computed from all data during the core Double-Blind (DB) study, and (2) for participants who had been assigned to perampanel in the core DB study, the pre-perampanel baseline was computed from the pre-randomization phase of the core DB study. The data is presented as percent responders.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 13, 2008)
Safety and tolerability will be examined based on the nature, frequency, and severity of adverse events, vital signs, 12-lead ECG abnormalities, chemistry and hematology laboratory test results. [ Time Frame: Assessments are done every 4 wks during the first 16 wks w/interim telephone contacts between visits. After 16 wks, they will be done every 12 wks w/interim telephone contacts in between. Subjects maintain seizure diary cards throughout entire study. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures
Official Title  ICMJE An Open-Label Extension Phase of the Double-Blind, Placebo-Controlled, Dose-Escalation, Parallel-Group Studies to Evaluate the Efficacy and Safety of E2007 (Perampanel) Given as Adjunctive Therapy in Subjects With Refractory Partial Seizures
Brief Summary The purpose of this study was to evaluate the safety and tolerability of perampanel (up to 12 mg/day) given as adjunctive treatment in subjects with refractory partial seizures and to evaluate the maintenance of effect of perampanel for the control of refractory partial seizures.
Detailed Description This was an open-label extension (OLE) study for subjects who completed one of the following double-blind, placebo-controlled, Phase 3 studies: E2007-G000-304 (NCT00699972), E2007-G000-305 (NCT00699582), and E2007-G000-306 (NCT00700310). This OLE study consisted of 2 phases: an Open-label Treatment Phase (comprised of a 16-week blinded Conversion Period and a 256-week Maintenance Period) and a Follow-up Phase (4 weeks). During the Conversion Period, subjects and investigators remained blinded to the treatment received in the previous DB study. To achieve this, all subjects continued to take 6 tablets of study medication (2 mg perampanel or matching placebo) or fewer as they were instructed during the core Double-Blind (DB) study. During the open-label Maintenance Period, subjects were treated with the perampanel dose that provided the best combination of individual efficacy and tolerability.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Epilepsy
Intervention  ICMJE Drug: perampanel
Perampanel 2 mg to 12 mg, once daily in the Open-Label Extension (OLE) study up to approximately 5 years
Study Arms  ICMJE Experimental: Perampanel
Participants previously receiving perampanel/placebo in the double blind-study, were titrated to receive perampanel 2 mg to 12 mg, once daily in the Open-Label Extension (OLE) study up to approximately 5 years.
Intervention: Drug: perampanel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 10, 2014)
1218
Original Estimated Enrollment  ICMJE
 (submitted: August 13, 2008)
1430
Actual Study Completion Date  ICMJE September 2014
Actual Primary Completion Date September 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Each participant who met the following criteria were enrolled in this study:

  1. Who completed Visit 8 of study E2007-G000-304, E2007-G000-305, or E2007-G000-306 and complied with the inclusion and exclusion criteria for that study (excluding criteria that are related to seizure occurrences).
  2. Provided written informed consent signed by participant or legal guardian prior to entering the study or undergoing any study procedures (If the written informed consent was provided by the legal guardian because the participant was unable to do so, a written or verbal assent from the participant was obtained).
  3. Who was considered reliable and willing to be available for the study period and record seizures and report adverse events them self or have a caregiver who can record and report the events for them.
  4. Females who were either of non-childbearing potential (defined as having undergone surgical sterilization, or postmenopausal [>age 50 and amenorrheic for 12 months]) or of childbearing potential. Females of childbearing potential were enrolled only if they agreed to be abstinent or continue using at least 1 medically acceptable method of contraception (eg, a double-barrier method [eg, condom + spermicide, condom + diaphragm with spermicide], IUD, or have a vasectomised partner) throughout the study period and for 2 months after the last dose of study drug. Women using hormonal contraceptives were required to use an additional approved method of contraception (as described previously) continuously throughout the entire study period and for 2 months after the last dose of study drug. (It was not required for male subjects to use contraceptive measures based on preclinical toxicology data).
  5. Continued to be treated with a stable dose of 1 or a maximum of 3 approved anti-epileptic drugs.

Exclusion Criteria:

Participants who met the following criteria were excluded from the study:

1. Those who, for any reason, discontinued early from the preceding double-blind study.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Chile,   China,   Czech Republic,   Estonia,   Finland,   France,   Germany,   Greece,   Hong Kong,   Hungary,   India,   Israel,   Italy,   Korea, Republic of,   Latvia,   Lithuania,   Malaysia,   Mexico,   Netherlands,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00735397
Other Study ID Numbers  ICMJE E2007-G000-307
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Eisai Inc.
Study Sponsor  ICMJE Eisai Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Michelle Gee, PhD. Eisai Limited
PRS Account Eisai Inc.
Verification Date February 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP