A Phase 3, Double-blind, Placebo-controlled, Randomized Discontinuation Study Followed by Open-label Extension Evaluating Efficacy and Safety of Amifampridine Phosphate in Patients With Lambert-Eaton Myasthenic Syndrome (LEMS)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 38
- 主要终点
- Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days
研究概览
简要总结
A Phase 3 study to evaluate the efficacy and safety of Amifampridine Phosphate in patients with Lambert-Eaton Myasthenic Syndrome (LEMS).
详细描述
This multicenter, double-blind, placebo-controlled, randomized (1:1) discontinuation study is a 4-part study designed to evaluate the efficacy and safety of multiple dose administration of amifampridine phosphate in patients with LEMS. Data from parts 2 and 3 (the double-blind parts of the study) are presented in this record.
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
- Double (Participant, Investigator)
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
- •Individuals eligible to participate in this study must meet all of the following inclusion criteria:
- •≥18 years of age
- •Confirmed diagnosis of LEMS
- •Normal respiratory function
- •Normal swallowing function
- •If receiving peripherally acting cholinesterase inhibitors a stable dose is required for at least 7 days prior to Screening.
- •If receiving oral immunosuppressants a stable dose is required for at least 90 days prior to Screening.
- •Negative pregnancy test for females of childbearing potential
- •If sexually active, willing to use 2 acceptable methods of contraception
- •Willing to perform all study procedures as physically possible.
- •Willing and able to provide written informed consent after the nature of the study has been explained and prior to the start of any research-related procedures.
排除标准
- •Individuals who meet any of the following exclusion criteria are not eligible to participate in the study:
- •History of epilepsy or seizure.
- •Known active brain metastasis.
- •Use of Fampridine (4-aminopyridine), and any form of 3,4-diaminopyridine other than the IP provided, such as amifampridine base or Firdapse, during the study.
- •Use of medications known to lower the epileptic threshold within 7 days or 5 half-lives.
- •Use of medications which inhibit neuromuscular junction function within 7 days or 5 half-lives.
- •Use of IVIG, plasmapheresis (plasma exchange), or immunoadsorption within 90 days
- •Use of guanidine hydrochloride within 7 days
- •Use of rituximab within 12 months
- •History of drug allergy to any pyridine-containing substances or any amifampridine phosphate excipient(s).
- •Use of any other investigational productwithin 30 days
- •Treatment with a concomitant medication that prolongs the QT/QTc interval within 7 days or 5 half-lives.
- •Treatment with sultopride (4-amino-N-[(1-ethylpyrrolidin-2-yl)methyl]-5-ethylsulfonyl-2-methoxybenzamide) within 7 days.
- •An abnormal electrocardiogram (ECG).
- •Documented history of arrhythmias.
- •History of additional risk factors for torsade de pointes.
- •Breastfeeding or pregnant or planning to become pregnant (self or partner) at any time during the study.
- •Likely or expected to require treatment for cancer within 3 months (90 days) after entering.
- •History of severe renal impairment or evidence of severe renal impairment
- •Any condition that places the patient at high risk of poor treatment compliance or of not completing the study.
- •History of uncontrolled asthma.
研究组 & 干预措施
Placebo
Matching placebo tablets administered 3-4 times a day (to the individual patient's tablet count of active at baseline) over 2 weeks.
干预措施: Placebo (Drug)
Amifampridine Phosphate
Amifampridine, 30-80 mg given 3-4 times per day with a maximum single dose of 20 mg (2 x 10 mg tablets), for 2 weeks.
干预措施: Amifampridine Phosphate (Drug)
结局指标
主要结局
Change From Baseline Quantitative Myasthenia Gravis (QMG) at 14 Days
时间窗: Assessment at Baseline and Day 14
The QMG is a physician-rated test including 13 assessments, including facial strength, swallowing, grip strength, and duration of time that limbs can be maintained in outstretched positions. Each of the 13 items is scored from 0 (none) to 3 (severe). The total score can range from 0 to 39. Increased QMG total score correlates to worsening symptoms of LEMS.
Change in SGI Score
时间窗: Assessment at Baseline and Day 14
Subject Global Impression (SGI) is a measure of changes in subject's perception of change in overall wellbeing. The patient is asked to use the 7-point scale below to rate their impression of the effects of the study medication during the preceding 3 days on their physical well being. 1. Terrible 2. Mostly dissatisfied 3. Mixed 4. Partially satisfied 5. Mostly satisfied 6. Pleased 7. Delighted
次要结局
- Change From Baseline Timed 25 Foot Walking Test (T25FW) at 14 Days(Assessment at Baseline and Day 14)
- Change in CGI-I Score(Baseline and Day 14)