A Multi-center, Open-label, Four-arm, Randomized Trial Evaluating the Safety and Tolerability of Brivaracetam Intravenous Infusion and Bolus, Administered in BID Regimen as an Adjunctive Antiepileptic Treatment in Subjects From 16 to 70 Years Suffering From Epilepsy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- UCB Pharma
- 入组人数
- 105
- 试验地点
- 17
- 主要终点
- Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
研究概览
简要总结
This is a multicenter, open-label, 4-arm, randomized, parallel-group study to evaluate safety and tolerability of Brivaracetam Intravenous (BRV iv) as adjunctive treatment for adults with epilepsy according to an initiation or a conversion scheme, during repeated dosing (100 mg/administration twice daily for 4.5 days).
详细描述
Eligible subjects will be randomized in a 1:1:1:1 ratio to the 4 treatment arms
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •An Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved written Informed Consent form signed and dated by the subject or by parent(s) or legal representative
- •Subjects from 16 to 70 years
- •Subjects with a body weight of >/= 40 kg
- •Female subjects without childbearing potential or female subjects with childbearing potential if they use a medically accepted contraceptive method
- •Subject/legal representative considered as reliable and capable of adhering to the protocol
- •Subjects with well-characterized focal or generalized epilepsy or epileptic syndrome
- •Subjects with a history of partial-onset seizures whether or not secondarily generalized or primary generalized seizures
- •Subjects being uncontrolled while treated with 1 to 2 permitted concomitant antiepileptic drugs (AEDs)
- •Permitted concomitant antiepileptic drugs (AEDs) and vagus nerve stimulation (VNS) being stable and at optimal dosage for the subject from at least 1 month before Visit 1 and expected to be kept stable during the Run-In and Evaluation Periods
排除标准
- •Mentally impaired subjects unable to understand the study purpose
- •History or presence of status epilepticus during 1 year preceding Visit 1 or Baseline
- •Subjects on felbamate with less than 18 months continuous exposure before Visit 1
- •Subjects currently on vigabatrin
- •Subject taking any drug with possible relevant central nervous system effects except is stable from at least 1 month before Visit 1 and expected to be kept stable during the trial
- •Subjects taking any drug that may significantly influence the metabolism of Brivaracetam (BRV) except if the dose has been kept stable at least 1 month before Visit 1, and is expected to be kept stable during the trial
- •History of cerebrovascular accident in the last 6 months
- •Subjects suffering from severe cardiovascular disease or peripheral vascular disease
- •Presence of any sign suggesting rapidly progressing brain disorder or brain tumor
- •Any clinical conditions which impair reliable participation in the study or necessitate the use of medication not allowed by protocol
- •Presence of a terminal illness
- •Presence of a serious infection
- •Subjects with a history of sever adverse hematologic reaction to any drug
- •Subjects suffering from severe disturbance of hemostasis
- •Impaired hepatic function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT) values of more than 3 times the upper limit of the reference range
- •Subjects having clinically significant deviations from reference range values for laboratory parameters: creatinine clearance calculated < 50 ml / min, platelets < 100,000 / µL, or neutrophil cells < 1,800 / µL
- •Clinically significant electrocardiogram (ECG) abnormalities according to the Investigator
- •History of suicide attempt
- •In the Investigator's medical judgment, any current suicidal ideation or other serious psychiatric disorders requiring of having required hospitalization or medication
- •Known allergic reaction or intolerance to pyrrolidone derivatives and / or investigational product excipients
- •Known multiple drug allergies or severe drug allergy
- •Pregnant or lactating women
- •Known alcohol or drug addiction or abuse within the last 2 years
- •Subject institutionalized under judicial decision
- •Problems of venous accessibility
- •Subject taking part in another clinical / pharmacological study in the month preceding enrollment (Visit 1)
- •Investigators, coinvestigators, their spouses or children, or any study collaborators
- •Subjects previously treated with Brivaracetam (BRV)
- •Subject previously screened within this study
研究组 & 干预措施
Placebo tablets / Brivaracetam bolus
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days.
Down-Titration:
- If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
- If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week
干预措施: Brivaracetam bolus (Drug)
Placebo tablets / Brivaracetam bolus
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) bolus for 4.5 days.
Down-Titration:
- If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
- If subject discontinues during the Evaluation Period or after Day 12, the subject will receive Placebo tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week
干预措施: Placebo (Other)
Brivaracetam (BRV) tablets / BRV bolus
Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days.
Down-Titration:
- If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
- If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week
干预措施: Brivaracetam tablets (Drug)
Brivaracetam (BRV) tablets / BRV bolus
Subjects will receive Brivaracetam (BRV) tablets for one week followed by BRV bolus for 4.5 days.
Down-Titration:
- If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
- If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake bid for the fourth week
干预措施: Brivaracetam bolus (Drug)
Placebo tablets / Brivaracetam infusion
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days.
Down-Titration:
- If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
- If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week
干预措施: Brivaracetam infusion (Drug)
Placebo tablets / Brivaracetam infusion
Subjects will receive Placebo (PBO) tablets for one week followed by Brivaracetam (BRV) intravenous infusion for 4.5 days.
Down-Titration:
- If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
- If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week
干预措施: Placebo (Other)
Brivaracetam (BRV) tablets / BRV infusion
Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days.
Down-Titration:
- If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
- If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week
干预措施: Brivaracetam tablets (Drug)
Brivaracetam (BRV) tablets / BRV infusion
Subjects will receive Brivaracetam (BRV) tablets for one week followed by Brivaracetam intravenous infusion for 4.5 days.
Down-Titration:
- If subject discontinues the study during the Run-In Period, then the subject will receive the treatment that he/she was assigned during Run-In
- If subject discontinues during the Evaluation Period or after Day 12, the subject will receive BRV tablets during Down-Titration:
Tablets will be provided for 4 weeks; 75 mg / intake BID for the first week, 50 mg / intake BID for the second week, 25 mg / intake BID for the third week, 10 mg / intake BID for the fourth week
干预措施: Brivaracetam infusion (Drug)
结局指标
主要结局
Number of Subjects With at Least One Treatment-emergent Adverse Event During the Study (Maximum 40 Days)
时间窗: 40 days
An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
次要结局
- Number of Subjects With at Least One Injection-related Treatment-emergent Adverse Event (TEAE) During the Evaluation Period.(4.5-day Evaluation Period)
- Number of Subjects Who Withdrew Due to a Treatment-emergent Adverse Event During the Study (Maximum 40 Days)(40 days)