A Sequential, Open-Label Study of the Pharmacokinetics and Safety of Intravenous Carbamazepine Relative to Oral Carbamazepine in Adult Patients With Epilepsy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Lundbeck LLC
- 入组人数
- 98
- 主要终点
- To assess the safety, tolerability and pharmacokinetics of IV CBZ as a 30- and 15-minute infusion relative to orally administered CBZ in adult patients with epilepsy.
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability and steady-state pharmacokinetics of intravenous (IV) Carbamazepine (CBZ) infusions relative to orally administered CBZ in adult patients with epilepsy.
详细描述
This phase 1, multicenter, sequential, open-label study was designed to assess the safety, tolerability and pharmacokinetics of IV CBZ relative to orally administered CBZ in adult subjects with epilepsy. The study design used an increasing dose/treatment escalation cohort paradigm wherein subjects were enrolled in a cohort based on their total daily dose (TDD) of oral CBZ and their calculated creatinine clearance (CLcr; calculated by the Cockroft-Gault equation) on Day -28. The purpose of the increasing dose/treatment escalation cohort design was to provide a means for the independent data monitoring committee (IDMC) to assess safety prior to enrolling in subsequent cohorts; data were summarized by infusion time, renal function and dose. The initial subjects enrolled had normal renal function (CLcr >= 80 mL/min) and were stable on oral dosing of CBZ from 400 mg/day to 800 mg/day. Subsequent Dosing Cohorts enrolled subjects on higher doses of oral CBZ and allowed subjects with some renal impairment to be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must be diagnosed with any of the approved epilepsy indications for CBZ that include: Partial seizures with complex symptomatology (psychomotor, temporal lobe); Generalized tonic clonic seizures (grand mal); Mixed seizure patterns that include one of the above; Other partial or generalized seizures.
- •Patient must be receiving a stable dose of oral CBZ (tablet or capsule formulation) for a minimum of 14 days prior to Day -
- •Patient must be receiving a constant dose of all other concomitant medications / device (including AEDs, Vagal Nerve Stimulator (VNS), OTC medications, and herbal supplements) that may not interfere with the metabolism of CBZ for a minimum of 14 days prior to Day -
- •No change in baseline AEDs are expected during the treatment period.
- •The patient must be able to comply with maintaining an accurate epilepsy medication dosing diary and seizure diary.
- •If female: Patient is not of childbearing potential.
- •If childbearing potential: Must have a negative serum pregnancy test at Day -28 and a negative serum pregnancy test on Day -1; Must comply with a method of birth control acceptable to the investigator (with the exception of hormone based contraceptives which are contraindicated with the use of CBZ).
排除标准
- •Patient is taking a daily oral dose of CBZ greater than 2000 mg per day.
- •Patient is being treated with hormone based therapy for birth control.
- •Patient has a QTc interval value that is greater than 450 msec.
- •Patient has a screening ALT, AST or bilirubin > 3 times the upper limit of normal.
- •Patients with CLCR < 30 mL/min or with a renal disorder (i.e. nephrotic syndrome, patients on hemodialysis or peritoneal dialysis or being considered for peritoneal or hemodialysis).
- •Patient is receiving oral CBZ for absence seizures.
- •Patient has had an episode of status epilepticus within 30 days of screening.
- •Patient has a history of severe or serious adverse reactions to CBZ (e.g. aplastic anemia, agranulocytosis).
- •Patient has been diagnosed with narrow angle glaucoma.
- •Patient weighs less than 50 kg.
结局指标
主要结局
To assess the safety, tolerability and pharmacokinetics of IV CBZ as a 30- and 15-minute infusion relative to orally administered CBZ in adult patients with epilepsy.
时间窗: 31 days
To compare the steady-state pharmacokinetics of intravenously administered CBZ (Day 7) relative to orally administered CBZ (Day 0).
时间窗: Day 7
次要结局
- To assess the safety, tolerability and pharmacokinetics of IV CBZ when administered over a 2-5-minute infusion in a subset of patients.(31 days)
- To assess the safety, tolerability and pharmacokinetics of IV CBZ in patients with mild or moderate renal impairment.(31 days)