Inpatient Double-Blind Placebo-Controlled Withdrawal Study of 3,4-Diaminopyridine Base (3,4-DAP) in Subjects With Known Lambert-Eaton Myasthenic Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 7
- 主要终点
- Number of Participants With 30% or More Deterioration in Triple Timed Up & Go (3TUG) Test, Compared to Time-matched Baseline
研究概览
简要总结
Hypothesis: 3,4-Diaminopyridine base (3,4-DAP) improves Lambert-Eaton Myasthenic Syndrome (LEMS)-related weakness.
详细描述
The objectives of the study were to confirm the safety and to test the efficacy of 3,4-DAP in the treatment of LEMS-related weakness.
This was a phase 2 randomized double-blind placebo-controlled withdrawal study in subjects with known clinically active LEMS who had been on a chronic stable dose of compassionate distribution Jacobus 3,4-DAP provided through FDA-approved individual investigator-held INDs.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age 18 or over
- •Ambulatory while taking 3,4-DAP, i.e. the patient was able to perform the timed up and go (TUG), either with or without an assistive device
- •Established diagnosis of LEMS, with documentation provided
- •Continuous use of Jacobus 3,4-DAP for at least 3 months
- •Minimum of 3 doses per day with no single dose less than 10 mg of 3,4-DAP
- •The patient needed to wait about 15 to 30 minutes to experience an unequivocal improvement in a LEMS-induced dysfunction after they take their first dose of 3,4-DAP in the morning [a patient who remains in bed past this point by choice may still be eligible]
- •Stable regimen of all LEMS-related treatments for at least 3 months
- •Stable daily regimen of other medications (prescription and over-the-counter) for a minimum of 1 month
- •Willing to chance being tapered off of 3,4-DAP
- •Fluency in English
- •If applicable, agreed to use birth control during heterosexual intercourse until at least 2 weeks after completion of study
- •A signed informed consent by the study subject
排除标准
- •Last monoclonal antibody treatment (e.g. rituximab) was less than 6 months ago (i.e., recent treatment is an exclusion)
- •Clinically significant or poorly controlled condition that in the opinion of the study personnel might pose an unacceptable risk to the patient if entered into the study
- •Respiratory failure requiring intubation while on 3,4-DAP with no precipitating event or medication
- •Use of any investigational drug other than 3,4-DAP within the last 30 days
- •Pregnant or lactating
- •Current use of other aminopyridines (e.g.4-AP) or guanidine
- •Did not display a sufficiently large response to 3,4-DAP during the baseline observation period in the CRU to detect a decline during withdrawal of 3,4-DAP
研究组 & 干预措施
Continuous 3,4-DAP
Subjects continued taking their usual individualized regimen of 3,4-DAP base, 30 to 100 mg daily divided into at least 3 doses.
干预措施: Continuous 3,4-DAP (Drug)
Taper 3,4-DAP to Placebo
Subjects were tapered over 3 days from their usual individualized regimen of 3,4-DAP base (30 to 100 mg daily divided into at least 3 doses) to placebo with up to an additional 16 hours of placebo before resuming their usual pre-study regimen of 3,4-DAP base
干预措施: Taper 3,4-DAP to Placebo (Drug)
结局指标
主要结局
Number of Participants With 30% or More Deterioration in Triple Timed Up & Go (3TUG) Test, Compared to Time-matched Baseline
时间窗: Baseline period (days 0, 1, 2); Randomized treatment period (starting with last dose of day 2, and days 3, 4, 5, and ending with first dose on day 6 when pre-randomization regimen was resumed, or rescue, if indicated sooner)
The 3TUG time obtained 2 hours after the last dose of the withdrawal period (i.e., at time of theoretical "peak drug effect") was compared to the average time-matched 3TUG tests performed during 2 days of baseline observation prior to randomization. The study endpoint was a change of more than 30% in the final post-dose 3TUG during the withdrawal period and was based on blinded readings of video recordings of 3TUG tests.
次要结局
- Self-assessment of LEMS-related Weakness, W-SAS(Participants were followed for up to 7 days)