A Double-Blind, Randomized, Placebo and Active Controlled Study to Evaluate the Efficacy and Safety of Once Daily, Extended Release Levetiracetam as Add-on Therapy in Patients with Refractory Partial Onset Epilepsy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 300
- 试验地点
- 16
- 主要终点
- Assess the reduction in weekly Focal Onset Seizures (FOS) frequency
研究概览
简要总结
This is a double-blind, randomized, placebo and active controlled study three arm to evaluate the efficacy and safety of levetiracetam XR as add-on therapy, in subjects with drug-resistant Focal onset epilepsy. This phase III trial consists of an initial 8-week observational period followed by a 12 week double blind period and a final 2 week safety follow up period . A total of 10 visits are planned for this study, of which 4 will be held by telephone and 6 at the study site. Overall, around 300 subjects will be screened across approximately 78 centres across Europe and India to obtain a total of 255 randomized subjects. Subjects will be randomized in a randomization ratio between levetiracetam IR 1000 mg per day, levetiracetam XR 1000 mg per day and placebo. The randomization will be stratified by age into two groups below 18 years and 18 years. Following screening, subjects will enter the 8 week observation period for the assessment of the seizure frequency to confirm their eligibility. All subjects must be on stable doses of anti-seizure medication for at least 4 weeks prior to the screening visit. Additionally, subjects had to show confirmed drug-resistant focal seizures despite 1 to 3 stable ASM, with at least 6 seizures during the initial 8 week observational period. During the 12 week treatment period, the investigational medicinal products will be administered swallowing the capsule and granules contained in the sachet with a sufficient amount of water, as one capsule in the morning; and one capsule plus one granule sachet at evening for all subjects, with or without food, for masking purposes and irrespective of their treatment arm. Subjects completing the 12 week double blind period will enter the 2 week safety period. Subjects who prematurely discontinue the treatment will complete the early termination visit as soon as possible.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Male and female, between 18 and above years of age, both inclusive.
- •Willingness and capability to provide informed consent form (ICF), be compliant with study procedures such as eDiary completion, be compliant with background anti-seizure medication (ASM) and Investigational Medicinal Product (IMP) intake.
- •Diagnosis of epilepsy with Focal-onset seizures (FOS) with or without secondary generalization according to the International League Against Epilepsy Classification of epileptic seizures.
- •On stable doses of ASM for at least 4 weeks prior to screening.
- •Confirmed drug-resistant FOS despite 1 to 3 stable ASM with at least 6 seizures during the 8 week observational period.
- •Patients who have Vagal Nerve Stimulator (VNS) must have stable settings more than 3 months prior to screening and expected to remain unchanged during the duration of the study.
- •Females of childbearing potential, if not abstinent, should use a highly effective double contraception, started 60 days prior to study entry and 30 days after end of study drug administration: a) Oral, injected or implanted hormonal methods of contraception.
- •b) Intrauterine device (IUD) c) Barrier methods: condom, diaphragm, spermicidal foam d) Male partner surgical sterilization (vasectomy) 8) Females of non-childbearing potential: either surgically sterilized (e.g. bilateral tubal ligation), had undergone hysterectomy or is at least 1 year postmenopausal (amenorrhea duration of at least 12 months) 9) Sexually active males with partner of childbearing potential commit to use an acceptable method of birth control consistently and correctly (oral, transdermal, systemic or implant contraception birth control, intrauterine devices) for 90 days after the last study drug administration.
排除标准
- •Presence of primary generalized epilepsies or seizures, such as absences, myoclonic epilepsies, Lennox Gastaut syndrome.
- •History of status epilepticus in the past 3 months prior to screening.
- •Seizure clusters where individual seizures cannot be counted.
- •History of non epileptic seizures.
- •Evidence of clinically significant disease (cardiac, respiratory, gastrointestinal, hepatic, hematologic or renal disease, neoplastic malignancies etc.) that in the opinion of the investigator could affect the subjects safety or trial conduct.
- •Neurodegenerative and other progressive neurological disorders.
- •Diagnosis of active psychiatric disease, except depressed subjects on stable doses of selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors for at least 12 weeks prior to screening.
- •History of prior suicide attempt or imminent risk of self harm based on investigators judgment or with a yes answer on item 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS).
- •History of drug abuse as defined by Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM V) and or positive drug screening other than prescribed drugs.
- •Alcohol abuse as per Diagnostic and Statistical Manual of Mental Disorders version 5 (DSM V) in the past year.
- •Positive for hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) or Human Immunodeficiency Virus (HIV) infection at screening.
- •Subjects presenting symptoms of coronavirus disease COVID
- •Known allergic reaction or intolerance to levetiracetam or other pyrrolidone derivatives or to any of the excipients.
- •Participation in a study involving administration of an investigational product within one month prior to screening or within five half lives of the previous study investigational compound, whichever is longer.
- •Women who are currently pregnant, who intend to become pregnant during the study, or who are breastfeeding.
- •Subjects with a diagnosis of Congenital Short QT Syndrome (SQTS).
- •The corrected QT interval by Fredericia (QTcF) more than and equal 450 msec in male and 470 msec in female subjects.
- •Laboratory values at screening: Platelets less than 100,000 per mm3 Absolute neutrophil count less than 1500 per mm3 Haemoglobin within 10.0g per dL Aspartate aminotransferase or alanine aminotransferase more than 3x upper limit of normal Estimated Glomerular Filtration Rate less than 80.
结局指标
主要结局
Assess the reduction in weekly Focal Onset Seizures (FOS) frequency
时间窗: Assess the reduction in Focal Onset Seizures (FOS) frequency in 8 Weeks.
of levetiracetam extended release (XR) compared to levetiracetam immediate release (IR) in
时间窗: Assess the reduction in Focal Onset Seizures (FOS) frequency in 8 Weeks.
subjects with drug resistant FOS
时间窗: Assess the reduction in Focal Onset Seizures (FOS) frequency in 8 Weeks.
次要结局
- assess the reduction in weekly FOS frequency of levetiracetam(XR compared to placebo in subjects with drug-resistant FOS.)
研究者
Koushik Ganguly
ERGOMED Clinical Research India Pvt Ltd