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A Efficacy and Safety Study of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01393743
Recruitment Status : Completed
First Posted : July 13, 2011
Results First Posted : January 11, 2016
Last Update Posted : August 28, 2017
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Tracking Information
First Submitted Date  ICMJE July 12, 2011
First Posted Date  ICMJE July 13, 2011
Results First Submitted Date  ICMJE May 29, 2015
Results First Posted Date  ICMJE January 11, 2016
Last Update Posted Date August 28, 2017
Study Start Date  ICMJE September 2011
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2017)
  • Median Percent Change in Primary Generalized Tonic Clonic Seizure Frequency (PGTC) Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study) [ Time Frame: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) ]
    Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days (as determined from participant diaries) was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change from baseline in PGTC seizure was analyzed over the Titration and Maintenance Periods combined, while baseline was defined as seizure frequency per 28 days based on all valid diary data during the Prerandomization Phase.
  • 50% Responder Rate for Primary Generalized Tonic Clonic Seizure During Maintenance - LOCF - (for Core Study) [ Time Frame: Baseline (4 or 8 weeks) and Maintenance (13 weeks) ]
    A responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance-last observation carried forward (LOCF) from prerandomization. The data was presented as the percentage of participants.
  • 50% Responder Rate in Primary Generalized Tonic-Clonic Seizure Frequency Per 28 Days Relative to the Core Study Prerandomization Phase - (for Extension Phase) [ Time Frame: Week 1 of perampanel treatment to date of last dose of perampanel in the Extension Phase ]
    Responder rate was defined as the percentage of participants who experienced a 50% or greater reduction in PGTC and total seizure frequency during treatment per 28 days relative to baseline (responder). Week 1 began on the date of first dose of the perampanel treatment regardless of whether it occurred in the Core Study or Extension Phase and continued to and included the date of the last dose of perampanel in the Extension Phase. For any given analysis window and seizure type(s), a 50% response from Core Study Prerandomization is a participant whose seizure frequency per 28 days for that seizure type(s) during that analysis window is 50% to 100% lower than his or her Core Study Prerandomization baseline seizure frequency per 28 days for that same seizure type(s). In Part B of the Extension Phase (after Visit 15), the seizure diary is only completed for days on which a seizure occurred and missing days were imputed as non-seizure days.
Original Primary Outcome Measures  ICMJE
 (submitted: July 12, 2011)
Percent change from baseline in PGTC seizure frequency per 28 days [ Time Frame: from baseline over the Titration and Maintenance Periods (17 weeks) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2017)
  • Median Percent Change in All Seizure Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study) [ Time Frame: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) ]
    Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change in seizure frequency relative to baseline (prerandomization) for all seizures (PGTC, myoclonic, absence and all other seizures that occur during the study) per 28 days during the Titration and Maintenance Periods combined was analyzed.
  • Median Percent Change in Primary Generalized Seizure Subtype Frequency Per 28 Days During the Titration and Maintenance Periods (Combined) Relative to Baseline (Prerandomization) - (for Core Study) [ Time Frame: Baseline (4 or 8 weeks), Titration (4 weeks), and Maintenance (13 weeks) ]
    Seizure frequency per 28 days was derived from the information recorded in the participant diaries. PGTC seizure frequency per 28 days was calculated as the number of PGTC seizures divided by the number of days in the interval and multiplied by 28. The percent change in seizure frequency relative to baseline (prerandomization) for primary generalized seizure subtype (myoclonic and absence) per 28 days during the Titration and Maintenance Periods combined was analyzed.
  • 50% Responder Rate for All Seizures During Maintenance-LOCF - (for Core Study) [ Time Frame: Baseline (4 or 8 weeks) and Maintenance (13 weeks) ]
    All seizures included PGTC, myoclonic, absence and all other seizures that occur during the study. A responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance- LOCF from prerandomization. The data was presented as percentage of participants.
  • 50% Responder Rate for Primary Generalized Seizure Subtype During Maintenance Period - LOCF - (for Core Study) [ Time Frame: Baseline (4 or 8 weeks) and Maintenance (13 weeks) ]
    Primary generalized seizure subtype included absence and myoclonic seizures. A responder was a participant who experienced a 50% or greater reduction in seizure frequency per 28 days during Maintenance - (LOCF) from prerandomization. The data was presented as the percentage of participants.
  • Percent Change From Core Study Prerandomization Phase in Primary Generalized Tonic-Clonic (PGTC) Seizure Frequency Per 28 Days - (for Extension Phase) [ Time Frame: Date of first dose of study drug to date of last dose of study drug in the Extension Phase ]
    Week 1 began on the date of first dose of the perampanel treatment regardless of whether it occurred in the Core Study or Extension Phase and continued to and included the date of the last dose of perampanel in the Extension Phase. For any given analysis window and seizure type(s), a 50% responder from Core Study Randomization is a participant whose seizure frequency per 28 days for that seizure type(s) during that analysis window is 50% to 100% lower than his or her Core Study Prerandomization baseline seizure frequency per 28 days for that same seizure type(s). In Part B of the Extension Phase (after Visit 15), the seizure diary is only completed for days on which a seizure occurred and missing days were imputed as non-seizure days.
  • Summary of Percent Change From Pre-Perampanel Baseline in Seizure Frequency Per 28 Days - (for Extension Phase) [ Time Frame: Weeks: 1 to 13, 14 to 26, 27 to 39, 40 to 52, 53 to 65, 66 to 78, 79 to 91, 92 to 104, 105 to 117, 118 to 130, 131 to 143, greater than or equal to 144 ]
    Efficacy assessments included seizure counts from participant diaries. The percent change in seizure frequency was assessed during the perampanel treatment duration, with the pre-perampanel baseline being used for evaluating the change. The pre-perampanel baseline was defined as follows: 1) for all participants who had been assigned to placebo treatment in the Core Study, the pre-perampanel baseline was computed from all valid seizure diary data during the Core Study, and 2) for participants who had been assigned to perampanel in the Core Study, the pre-perampanel baseline was computed from all valid seizure diary data during the Prerandomization Phase plus the 4 weeks prior to the Prerandomization Phase of the Core Study. The perampanel treatment duration consisted of: 1) the Randomization Phase of the Core Study plus the Extension Phase for participants assigned to perampanel in the Core Study, and 2) the Extension Phase for participants assigned to placebo in the Core Study.
  • Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events as a Measure of Safety and Tolerability of Perampanel in Subjects With Inadequately Controlled PGTC Seizures - (for Core Study) [ Time Frame: For each participant, from the first treatment dose till 30 days after the last dose or up to 21 weeks for core study and 142 weeks for extension phase. ]
    An Adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered an investigational product. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening (i.e., the subject 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 a congenital anomaly/birth defect (in the child of a subject who was exposed to the study drug). In this study, treatment emergent adverse events (TEAEs) (defined as an AE 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 Secondary Outcome Measures  ICMJE
 (submitted: July 12, 2011)
Responder Rate for all subtypes of primary generalized seizure frequency per 28 days [ Time Frame: Maintenance Period relative to baseline (17 weeks) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Efficacy and Safety Study of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures
Official Title  ICMJE A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Adjunctive Perampanel in Primary Generalized Tonic Clonic Seizures
Brief Summary This study is designed to evaluate the efficacy, safety, and pharmacokinetics (PK) of perampanel on Primary Generalized Tonic Clonic (PGTC) seizure frequency in adolescents and adults maintained on one to two stable antiepileptic drugs (AED).
Detailed Description This study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, adjunctive-therapy study with an open-label Extension Phase. The Core Study consists of 2 phases: Prerandomization and Randomization. The Prerandomization Phase consisted of 2 periods: Screening (up to 4 weeks) and Baseline (4 or 8 weeks, depending on the accuracy of diary-documented seizures during Screening), during which participants will be assessed for eligibility to participate in the study. The Randomization Phase consisted of 3 periods: Titration (4 weeks), Maintenance (13 weeks), and Follow-up (4 weeks; only for those participants not entering into the Extension Phase). At the start of the Randomization Phase, eligible participants will be randomized to the perampanel or placebo treatment groups in a 1:1 ratio. The extension phase consists of 142 weeks.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Seizure Disorder Generalized Tonic Clonic
Intervention  ICMJE
  • Drug: Perampanel
    Other Name: E2007
  • Drug: Placebo comparator
Study Arms  ICMJE
  • Experimental: Perampanel
    Participants received 6 tablets (initially 1 tablet of 2-mg perampanel plus 5 tablets of perampanel matched placebo) and up-titrated weekly in 2-mg increments to a target dose range of 8 mg per day maintaining the blind with administration of 6 tablets per day of either perampanel/placebo.
    Intervention: Drug: Perampanel
  • Placebo Comparator: Placebo
    Participants received 6 tablets of perampanel matched placebo, once a day.
    Intervention: Drug: Placebo comparator
Publications * French JA, Krauss GL, Wechsler RT, Wang XF, DiVentura B, Brandt C, Trinka E, O'Brien TJ, Laurenza A, Patten A, Bibbiani F. Perampanel for tonic-clonic seizures in idiopathic generalized epilepsy A randomized trial. Neurology. 2015 Sep 15;85(11):950-7.

*   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: July 27, 2017)
163
Original Estimated Enrollment  ICMJE
 (submitted: July 12, 2011)
165
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date May 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion:

  1. Clinical diagnosis of PGTC seizures (with or without other subtypes of primary generalized seizures) and experiencing greater than or equal to 3 PGTC seizures during the 8-week period prior to randomization
  2. Have had a routine electroencephalogram (EEG) prior to or during the Baseline Period with electroencephalographic features consistent with primary generalized epilepsy; other concomitant anomaly should be explained by adequate past medical history
  3. On a fixed dose of one to a maximum of three concomitant antiepileptic drugs (AEDs) for a minimum of 30 days prior to Baseline; only one inducer AED (i.e., carbamazepine, oxcarbazepine, or phenytoin) out of the maximum of two AEDs will be allowed
  4. A vagal nerve stimulator (VNS) will be allowed, but it must have been implanted greater than or equal to 5 months prior to Baseline (stimulator parameters cannot be changed for 30 days prior to Baseline and for the duration of the study).
  5. Have had a computed tomography (CT) or magnetic resonance imaging (MRI) within the last 10 years (for adults) and 5 years (for adolescents) that ruled out a progressive cause of epilepsy
  6. A ketogenic diet will be allowed as long as the participant has been on this diet for 5 weeks prior to randomization

Exclusion:

  1. A history of status epilepticus that required hospitalization within 12 months prior to Baseline
  2. Seizure clusters where individual seizures cannot be counted
  3. A history of psychogenic seizures
  4. Concomitant diagnosis of Partial Onset Seizures (POS)
  5. Progressive neurological disease
  6. Clinical diagnosis of Lennox-Gastaut syndrome
  7. If felbamate is used as a concomitant AED, participants must be on felbamate for at least 2 years, with a stable dose for 60 days prior to Baseline. They must not have a history of white blood cell (WBC) count below less than or equal to 2500/microL (2.50 1E+09/L), platelets less than 100,000/microL, liver function tests (LFTs) greater than 3 times the upper limit of normal (ULN), or other indication of hepatic or bone marrow dysfunction while receiving felbamate.
  8. Concomitant use of vigabatrin: Participants who took vigabatrin in the past must be discontinued for approximately 5 months prior to Baseline, and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test
  9. Concomitant use of barbiturates (except for seizure control indication) within 30 days prior to Baseline
  10. Use of intermittent rescue benzodiazepines (i.e., one to two doses over a 24-hour period considered one-time rescue) two or more times within the 30 days prior to Baseline
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 Not Provided
Removed Location Countries Australia,   Austria,   China,   Czech Republic,   France,   Germany,   Greece,   Hungary,   India,   Israel,   Japan,   Korea, Republic of,   Latvia,   Lithuania,   Netherlands,   Poland,   Serbia,   Thailand,   United States
 
Administrative Information
NCT Number  ICMJE NCT01393743
Other Study ID Numbers  ICMJE E2007-G000-332
Has Data Monitoring Committee Not Provided
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: Francesco Bibbiani Eisai Inc.
PRS Account Eisai Inc.
Verification Date July 2017

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