PARTIAL ONSET SEIZURES

本試驗主要目標為，評估兩種劑量濃度的pregabalin相較於安慰劑作為1個月至未滿4歲兒童受試者輔助性治療時，在降低部份癲癇發作頻率的療效。

PREGABALIN

Pregabalin

oral solution

20mg

主要療效指標

 主要療效指標將是由中央讀取人員判定雙盲期第6次回診時收集所有部份癲癇發作的雙盲24小時癲癇發作率對數轉換(48小時影像EEG評估期)。將以下列方式計算雙盲期的此項24小時癲癇率：

雙盲24小時EEG癲癇發作率= 雙盲48小時評估期的癲癇發作次數 x 24
影像EEG監測的小時數

 使用對數轉換時，所有受試者的雙盲24小時EEG癲癇發作率將加入1/28的數字，代表癲癇發作發生率可能為「0」的任何情況。此將得出下列主要療效數據：loge (雙盲24小時EEG癲癇率+ 1/28)。將以相對於安慰劑的「癲癇發作率百分比變化」提出報告。例如，其中一種pregabalin劑量與安慰劑之間的-0.400雙盲24小時癲癇發作率對數轉換差異，相當於pregabalin組的雙盲24小時EEG癲癇發作率較安慰劑組減少33% (即：100% x [exp-0.400 - 1] = -33%))。
 將需要至少24小時的可評估影像EEG才可使用EEG。若可評估影像EEG未滿24小時，則將癲癇發作率資料視為遺失。

 將以相同方式計算基期24小時EEG癲癇發作率。

次要療效指標

 反應者比例，定義為雙盲48小時EEG期間部份癲癇發作率為自基期以來減少≥ 50%的受試者。符合此條件的受試者將被認定為反應者。

安全性試驗指標

 安全性評估將包括不良事件(AE)資料(發生率、性質、嚴重程度，以及與試驗藥物的關係)、臨床實驗室資料以及身體理學檢查的評估、生命徵象、神經學檢查與心電圖(ECG)。

Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriately qualified member
of the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the
study:
1. Evidence of a personally signed and dated informed consent document indicating that
the parent(s)/guardian(s) have been informed of all pertinent aspects of the study.
When there are 2 parents, or 2 guardians, consent should be obtained from both of the
child’s parents/guardians if present at the meeting where the informed consent
document is signed.
2. Subjects and Parent(s)/guardian(s)/caregiver(s) who are willing and able to comply
with scheduled visits, treatment plan, laboratory tests, and other study procedures.
3. Male and female subjects, 1 month (44 weeks gestational age) through <4 years of
age inclusive on the date of the Screening Visit with a diagnosis of epilepsy withseizures classified as simple partial, complex partial or partial becoming secondarily
generalized, according to the International League Against Epilepsy (ILAE 20103
see Appendix 1) Diagnosis must be established by:
 Subject’s seizure history (eg, description of seizures excluding confounding
disorders such as pseudoseizures etc), family history and neurological exam.
 Subjects must have previously had a contrast enhanced computed tomography
(CT) or magnetic resonance imaging (MRI) scan of the brain and EEG testing.
Results must be consistent with the diagnosis of focal onset epilepsy and must
demonstrate that no abnormality is likely to be progressive .
 In the event that a CT or MRI scan is needed, it should be performed as soon
as possible after Visit 1 if it cannot be performed the day of this visit and must
be completed and reviewed prior to randomization.
4. Currently receiving a stable dose of 1 to 3 antiepileptic drugs (stable within 7 days
prior to screening). Benzodiazepine medication used on a regular basis at a stable
dosage will be considered 1 of the concurrent antiepileptic treatments, Vagus Nerve
Stimulator when present will also be considered 1 of the concurrent antiepileptic
treatments.
5. A 12-lead ECG at screening without clinically significant abnormal findings as
determined by the investigator. Potentially clinically significant abnormal findings
will be reviewed by a pediatric cardiologist at the central ECG laboratory.
6. Subjects must have had at least 3 observed seizures in the month prior to screening.
7. Subjects must have at least 2 partial onset seizures as determined by the investigator
or designee during the 48 hour baseline Video-EEG phase.
Exclusion Criteria
Subjects presenting with any of the following will not be included in the study:
1. Primary generalized seizures (including in the setting of co-existing partial onset
seizures) which may include, for example:
 Clonic, tonic, and clonic-tonic seizures (note that partial onset seizures that
become secondarily generalized are not exclusionary).
 Absence seizures.
 Infantile spasms.
 Myoclonic, myoclonic atonic, myoclonic tonic seizures.
2. Lennox-Gastaut syndrome, Benign Epilepsy with Centrotemporal Spikes (BECTS)
and Dravet syndrome.
3. A current diagnosis of febrile seizures or seizures related to an ongoing acute medical
illness.
4. Exacerbation of partial onset seizures due to fever occurring within 60 days of
screening.
5. Status epilepticus within 1 year prior to screening.
6. Seizures related to acute medical illness.
7. Any change in AED regimen (type of medication or dose) within 7 days of the
Screening Visit or during the Baseline Phase.
8. Progressive structural central nervous sytem (CNS) lesion or a progressive
encephalopathy.
9. Progressive errors of metabolism.
10. Known or suspected chronic hematologic, hepatic or renal disease (AST and ALT)
above 3 times the upper limit of normal (ULN); or bilirubin, BUN, or creatinine
above 2 times the ULN within the previous 6 months prior to screening). Subjects
who experienced neonatal hyperbilirubinemia may be included after consulting with
the study clinician.
11. Estimated creatinine clearance (ClCR) <80 mL/min/1.73 m2 (see Section 7.4.1).
12. Subjects whose parents/caregivers are investigational site staff members directly
involved in the conduct of the trial or otherwise supervised by the Investigator.
13. Participation in other studies involving investigational drug(s) (Phases 1-4) within
30 days before the current study begins and/or during study participation.
14. Other severe acute or chronic medical, psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of the
study results or in the judgment of the investigator, would make the subject
inappropriate for entry into this study. Patients with complex medical histories,
including genetic or chromosomal syndromes, should be discussed with the study
clinician prior to screening.
15. The concomitant use of gabapentin, felbamate, and vigabatrin is prohibited.
16. Previous treatment of epilepsy with pregabalin.
17. Weight >30.0 kg.