A Phase II, Double-Blind, Randomized, Three-Way Crossover, Placebo-Controlled, Pharmacodynamic Study of CK-2017357 in Patients With Generalized Myasthenia Gravis on Standard Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 32
- 试验地点
- 15
- 主要终点
- Pulmonary Function Test (VC in liters)
研究概览
简要总结
The primary objective of this early-stage clinical study is to demonstrate an effect of single doses of CK-2017357 on measures of skeletal muscle function and fatigability in patients with generalized myasthenia gravis (MG).
详细描述
This study is a Phase II, double-blind, randomized, three-way crossover, placebo-controlled, PD study of CK-2017357 in patients with generalized MG on standard therapy. 36 to 78 patients will be randomized at approximately 15 study centers to one of six different treatment sequences. Each treatment sequence consists of three dosing periods in which patients receive single oral doses of placebo, 250 mg, and 500 mg of CK-2017357. All six treatment sequences will enroll 6 patients. A wash out period of at least 7 days (to a maximum of 10 days) will be employed between the individual doses for each patient. This study is designed to assess the effects of CK-2017357 on the standardized Quantitative Myasthenia Gravis (QMG) score, Manual Muscle Test, Myasthenia Gravis Composite Assessment (MGCA) and Forced Vital Capacity. The pharmacokinetic (PK) and pharmacodynamic (PD) relationship of CK-2017357 after two single doses will be assessed versus placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treatment Sequence 1
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
干预措施: Placebo (Drug)
Treatment Sequence 1
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
干预措施: 250 mg CK-2017357 (Drug)
Treatment Sequence 3
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
干预措施: Placebo (Drug)
Treatment Sequence 1
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 CK-2017357 500 mg
干预措施: 500 mg CK-2017357 (Drug)
Treatment Sequence 2
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
干预措施: Placebo (Drug)
Treatment Sequence 2
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
干预措施: 250 mg CK-2017357 (Drug)
Treatment Sequence 2
Dosing Period 1 Placebo; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 CK-2017357 250 mg
干预措施: 500 mg CK-2017357 (Drug)
Treatment Sequence 3
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
干预措施: 250 mg CK-2017357 (Drug)
Treatment Sequence 3
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 500 mg
干预措施: 500 mg CK-2017357 (Drug)
Treatment Sequence 4
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
干预措施: Placebo (Drug)
Treatment Sequence 4
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
干预措施: 250 mg CK-2017357 (Drug)
Treatment Sequence 4
Dosing Period 1 CK-2017357 250 mg; Dosing Period 2 CK-2017357 500 mg; Dosing Period 3 Placebo
干预措施: 500 mg CK-2017357 (Drug)
Treatment Sequence 5
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
干预措施: Placebo (Drug)
Treatment Sequence 5
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
干预措施: 250 mg CK-2017357 (Drug)
Treatment Sequence 5
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 Placebo; Dosing Period 3 CK-2017357 250 mg
干预措施: 500 mg CK-2017357 (Drug)
Treatment Sequence 6
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
干预措施: Placebo (Drug)
Treatment Sequence 6
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
干预措施: 250 mg CK-2017357 (Drug)
Treatment Sequence 6
Dosing Period 1 CK-2017357 500 mg; Dosing Period 2 CK-2017357 250 mg; Dosing Period 3 Placebo
干预措施: 500 mg CK-2017357 (Drug)
结局指标
主要结局
Pulmonary Function Test (VC in liters)
时间窗: 1 day
Forced Vital Capacity
Manual Muscle Test (MMT)
时间窗: 1 day
Sum of strength or function values assessed by physician on the neck, shoulder, hip and ankle
Quantitative Myasthenia Gravis score (QMG)
时间窗: 1 day
A quantitative motor assessment of muscular weakness on a scale of 0 to 3 with 0 representing "none" and 3 representing "severe". Muscular assessments included in the overall score are effects on double vision, ptosis, facial muscles, swallowing, speech, outstretched arms and legs, forced vital capacity, hand grip strength, and ability to lift head.
次要结局
- Characterize dose and plasma concentrations of CK-2017357 and QMG(2 days)
- Characterize dose and plasma concentrations of CK-2017357 and Manual Muscle Test (MMT)(2 days)
- Number of patients with adverse events(4 weeks)
- Patient Global Assessment(2 days)
- Investigator Global Assessment(2 days)
- Modified MG Symptom Score(2 days)
- Characterize dose and plasma concentrations of CK-2017357 and Forced Vital Capacity (FVC)(2 days)