Clinical trial NCT03201900: Study for Verification of Efficacy and Safety for Perampanel Monotherapy in Untreated Participants With Partial Onset Seizures (Including Secondarily Generalized Seizures (FREEDOM Study)
Official title: A Multicenter, Uncontrolled, Open-label Study and Extension Study for Verification of Eefficacy and Safety for Perampanel Monotherapy in Untreated Patients With Partial Onset Seizures (Including Secondarily Generalized Seizures) (FREEDOM Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Partial Onset Seizures
Keywords: perampanel
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2017-06-28
Enrollment: 91
Sex: ALL
Minimum age (years): 12
Maximum age (years): 74
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is conducted to evaluate the seizure-free rate of the 26-week Maintenance Period in untreated participants with partial onset seizures (POS).


Eligibility criteria: Inclusion Criteria:

* Be considered reliable and willing to be available for the study period and are able to record seizures and report adverse events (AEs) himself/herself or have a caregiver who can record seizures and report AEs for them
* Participants who are newly diagnosed or recurrent epilepsy and have experienced at least 2 unprovoked seizures separated by a minimum of 24 hours in the 1 year prior to the Pretreatment Phase
* Participants who have excluded the progressive central nervous system (CNS) abnormality occurring seizures by computed tomography (CT) or magnetic resonance imaging (MRI)
* Participants who have had a diagnosis of epilepsy with partial seizures with or without secondarily generalized seizures according to the International League Against Epilepsy (ILAE) Classification of Epileptic Seizures (1981). Diagnosis should have been established by clinical history and an electroencephalogram (EEG) that is consistent with localization-related epilepsy; normal interictal EEGs will be allowed provided that the participant meets the other diagnosis criterion (ie, clinical history)

Exclusion Criteria:

* Participants who present only simple partial seizures without motor signs
* Participants who have seizure clusters where individual seizures cannot be counted
* Participants who present or have a history of Lennox-Gastaut syndrome
* Participants who have a history of status epilepticus
* Participants who have a history of psychogenic non-epileptic seizures
* Participants who have a history of suicidal ideation/attempt
* Participants who present clinically problematic psychological or neurological disorder(s)
* Evidence of clinically significant disease
* Evidence of clinically significant active hepatic disease
* A prolonged time from the beginning of the QRS complex to the end of the T wave (QT) interval corrected for heart rate
* Participants who have a history of receiving any AEDs (except for AEDs used as rescue treatment), antipsychotics or anti-anxiety drugs within 12 weeks prior to the Pretreatment Phase
* Participants who have not used a stable dose of antidepressant in the 12 weeks
* Participants who have a history of any type of surgery for brain or central nervous system within 1 year
* Participants who have a history of receiving any AED (including AED used as rescue treatment) for more than 2 weeks
* Participants who have used intermittent rescue benzodiazepines on 2 or more occasions within 4 weeks
* Participants who have a history of receiving any AED polytherapy
* Participants who experienced treatment with perampanel
* Participants who have had non-constant ketogenic diet within 4 weeks
* Participants who have a history of drug or alcohol dependency or abuse
* Participants who have had multiple drug allergies or a severe drug reaction to an AED(s)
* Females who are breastfeeding or pregnant in the Pretreatment Phase (as documented by a positive beta-human chorionic gonadotropin \[β-hCG\] test)
* Females of childbearing potential who:

  * Within 28 days before the start of the Pretreatment Phase, did not use a highly effective method of contraception, which includes any of the following:

    * total abstinence (if it is their preferred and usual lifestyle);
    * an intrauterine device or intrauterine hormone-releasing system (IUS);
    * a contraceptive implant;
    * an oral contraceptive (with additional barrier method) (Participant must be on a stable dose of the same oral contraceptive product for at least 28 days before dosing and throughout the study and for 28 days after study drug discontinuation);
    * have a vasectomized partner with confirmed azoospermia
  * Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation
* Participants who have participated in a study involving administration of an investigational drug or device within 4 weeks before Visit 1, or within approximately 5 half-lives of the previous investigational compound, whichever is longer

Primary outcomes:
measure: Percentage of Participants With Partial-onset Seizures (POS) Who Achieved Seizure-free Status During the 26-week Maintenance Period of 4 mg Perampanel
timeFrame: 26 weeks in Maintenance Period of 4 mg perampanel
Secondary outcomes:
measure: Percentage of Participants With POS Who Achieved Seizure-free Status During the 26-week Maintenance Period of Last Evaluated Dose of 4 or 8 mg Perampanel
timeFrame: 26 weeks in Maintenance Period of 4 or 8 mg perampanel
measure: Percentage of Participants With POS Who Achieved Seizure-free Status During the 52-week Treatment Phase (26-week Maintenance Period Plus 26-week Extension Phase) of 4 mg of Perampanel
timeFrame: 52-week (Maintenance Period of 4 mg perampanel + Extension Phase of 4 mg perampanel)
measure: Percentage of Participants With POS Who Achieved Seizure-free Status During the 52-week of Treatment Phase (26-week Maintenance Period Plus 26-week Extension Phase) of Last Evaluated Dose of 4 or 8 mg Perampanel
timeFrame: 52-week (Maintenance Period of last evaluated dose of 4 or 8 mg perampanel + Extension Phase of 4 or 8 mg perampanel)
measure: Time to Onset of First Seizure From the First Dose of Study Drug in the Maintenance Period of 4 mg Perampanel
timeFrame: From the first dose of study drug in the Maintenance Period (Week 6) up to the first seizure onset (up to 150 weeks)
measure: Time to Onset of First Seizure From the First Dose of Study Drug in the Maintenance Period of Last Evaluated Dose of 4 or 8 mg Perampanel
timeFrame: From the first dose of study drug in the Maintenance Period (Week 6) up to the first seizure onset (up to 150 weeks)
measure: Time to Withdrawal From the First Dose of Study Drug in the Maintenance Period of 4 mg Perampanel
timeFrame: From the first dose of study drug in the Maintenance Period (Week 6) up to the date of first withdrawal, regardless of reason (up to 150 weeks)
measure: Time to Withdrawal From the First Dose of Study Drug in the Maintenance Period of Last Evaluated Dose of 4 or 8 mg Perampanel
timeFrame: From the first dose of study drug in the Maintenance Period (Week 6) up to the date of first withdrawal, regardless of reason (up to 150 weeks)
measure: Number of Participants With Any Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Event (TESAEs), and TEAEs Leading to Discontinuation of the Study Drug
timeFrame: From baseline up to 28 days after last dose of study drug (up to 160 weeks)
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: Eisai Trial Site #18
city: Aichi
country: Japan
facility: Eisai Trial Site #19
city: Fukuoka
country: Japan
facility: Eisai Trial Site #11
city: Fukuoka
country: Japan
facility: Eisai Trial Site #29
city: Hiroshima
country: Japan
facility: Eisai Trial Site #4
city: Hokkaido
country: Japan
facility: Eisai Trial Site #16
city: Hokkaido
country: Japan
facility: Eisai Trial Site #8
city: Hyogo
country: Japan
facility: Eisai Trial Site #14
city: Hyogo
country: Japan
facility: Eisai Trial Site #6
city: Kagoshima
country: Japan
facility: Eisai Trial Site #7
city: Kanagawa
country: Japan
facility: Eisai Trial Site #9
city: Kyoto
country: Japan
facility: Eisai Trial Site #10
city: Miyagi
country: Japan
facility: Eisai Trial Site #30
city: Nagasaki
country: Japan
facility: Eisai Trial Site #25
city: Nagasaki
country: Japan
facility: Eisai Trial Site #27
city: Nara
country: Japan
facility: Eisai Trial Site #15
city: Niigata
country: Japan
facility: Eisai Trial Site #12
city: Osaka
country: Japan
facility: Eisai Trial Site #21
city: Osaka
country: Japan
facility: Eisai Trial Site #24
city: Osaka
country: Japan
facility: Eisai Trial Site #26
city: Saitama
country: Japan
facility: Eisai Trial Site #3
city: Saitama
country: Japan
facility: Eisai Trial Site #5
city: Shizuoka
country: Japan
facility: Eisai Trial Site #1
city: Tochigi
country: Japan
facility: Eisai Trial Site #22
city: Tokushima
country: Japan
facility: Eisai Trial Site #28
city: Tokyo
country: Japan
facility: Eisai Trial Site #20
city: Tokyo
country: Japan
facility: Eisai Trial Site #23
city: Tokyo
country: Japan
facility: Eisai Trial Site #31
city: Yamagata
country: Japan
facility: Eisai Trial Site #13
city: Yamaguchi
country: Japan
facility: Eisai Trial Site #17
city: Yamaguchi
country: Japan
facility: Eisai Trial Site #32
city: Gyeonggi-do
country: Korea, Republic of
facility: Eisai Trial Site #38
city: Incheon
country: Korea, Republic of
facility: Eisai Trial Site #36
city: Seoul
country: Korea, Republic of
facility: Eisai Trial Site # 2
city: Seoul
country: Korea, Republic of
facility: Eisai Trial Site #33
city: Seoul
country: Korea, Republic of
facility: Eisai Trial Site #34
city: Seoul
country: Korea, Republic of
facility: Eisai Trial Site #35
city: Seoul
country: Korea, Republic of
facility: Eisai Trial Site #37
Study officials:
References:
citation: Husni RE, Ngo LY, Senokuchi H, Patten A, Hiramatsu H, Watanabe K, Yamamoto T. Experience of perampanel monotherapy beyond initial titration to achieve seizure freedom in patients with focal-onset seizures with newly diagnosed or currently untreated recurrent epilepsy: A post hoc analysis of the open-label Study 342 (FREEDOM). Epilepsia Open. 2022 Mar;7(1):59-66. doi: 10.1002/epi4.12551. Epub 2021 Nov 19.