A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
2019年5月7日 更新者：Cytokinetics
A Phase II, Double-Blind, Randomized, Placebo-Controlled, Three-Way Crossover, Pharmacokinetic and Pharmacodynamic Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
The primary objective of this study is to demonstrate a pharmacodynamic effect of CK 2017357 on measures of skeletal muscle function or fatigability in patients with ALS.
研究概览
详细说明
This study is a Phase II, double-blind, randomized, placebo-controlled, three-way crossover study of CK-2017357 in patients with ALS.
36 to 72 patients will be randomized to one of six different treatment sequences.
Each treatment sequence consists of three dosing periods; in each dosing period¸ patients receive a single oral dose of placebo, 250 mg of CK-2017357, or 500 mg of CK-2017357.
All six treatment sequences will enroll approximately the same number of patients.
A washout period of at least 6 days (to a maximum of 10 days) will be employed between the doses for each patient.
This study is designed to assess the effect of CK-2017357 on maximal voluntary muscle strength, on the development of fatigue at maximal and sub-maximal voluntary muscle contraction, and on selected pulmonary function parameters.
The plasma concentration of CK-2017357 will be measured at selected time points after each of two single doses of CK-2017357 in men and women.
The plasma concentration versus time data obtained in this study may be used to develop a population PK model and estimate inter-subject variability of PK parameters in this target patient population, in particular between male and female study patients.
研究类型
介入性
注册 (实际的)
67
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Arizona
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Phoenix、Arizona、美国、85018
- Phoenix Neurological Associates, Ltd.
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California
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Fresno、California、美国、93701
- University Neurology Associates
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San Francisco、California、美国、94115
- California Pacific Medical Center
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Florida
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Jacksonville、Florida、美国、32224
- Mayo Clinic Florida
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Kentucky
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Lexington、Kentucky、美国、40536
- University of Kentucky
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Maryland
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Baltimore、Maryland、美国、21287
- Johns Hopkins Hospital
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Massachusetts
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Boston、Massachusetts、美国、02114
- Massachusetts General Hospital
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Missouri
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Saint Louis、Missouri、美国、63110
- Washington University
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New York
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Syracuse、New York、美国、13210
- SUNY Upstate Medical Center
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North Carolina
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Durham、North Carolina、美国、27705
- Duke University
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Oregon
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Portland、Oregon、美国、97213
- Providence ALS Center
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19102
- Drexel University College of Medicine, Dept of Neurology
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University Park、Pennsylvania、美国、17033
- Penn State
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Texas
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San Antonio、Texas、美国、78229
- The University of Texas Health Science Center at San Antonio
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Vermont
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Burlington、Vermont、美国、05401
- University of Vermont
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria
For enrollment, patients were required to satisfy all of the following criteria at baseline:
1. Able to comprehend and willing to sign an Informed Consent Form (ICF)
- A diagnosis of familial or sporadic ALS (defined as meeting the possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS according to the World Federation of Neurology El Escorial criteria) (Brooks, Miller et al. 2000)
- Males or females 18 years of age or older
- Body Mass Index (BMI) of 18.0 to 30.0 kg/m2, inclusive
- Maximum voluntary grip strength in at least one hand between 10 and 40 pounds (females) or 10 and 60 pounds (males)
- Able to swallow capsules with water
- Upright Slow Vital Capacity (SVC) > 40% of predicted for age, height, and sex [See Appendix 16.6.1]
- Able to perform pulmonary function tests
- Pre-study clinical laboratory findings (including troponin I [TnI] and creatine phosphokinase [CPK]) within normal range, or, if outside of the normal range, deemed not clinically significant by the Investigator
- For female patients only: The patient is post-menopausal (≥ 1 year) or sterilized, or if she is of childbearing potential, she is not breastfeeding, her pregnancy test is negative, she has no intention to become pregnant during the course of the study, and she is using contraceptive drugs or devices for the duration of the study and for 10 weeks after the end of the study.
For male patients only: Male patients agree for the duration of the study and 10 weeks after the end of the study to use a condom during sexual intercourse with female partners who are of reproductive potential and to have female partners use an additional effective means of contraception (e.g., diaphragm plus spermicide or oral contraceptives) or the male patient must agree to abstain from sexual intercourse for 10 weeks after the end of the study.
Exclusion Criteria
Patients satisfying any of the following criteria at baseline were excluded from enrollment:
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 times the upper limit of normal (ULN)
- Life expectancy < 3 months
- Participation in any trial in which receipt of investigational study drug occurred within 30 days prior to dosing
- Any prior treatment with CK-2017357
- In the opinion of the Investigator, the patient is not suitable to participate in the study
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：交叉作业
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Treatment Sequence 1
Treatment sequence 1 consisted of three dosing periods in which patients received single oral doses of placebo, 250 mg, and 500 mg of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
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胶囊中的匹配安慰剂作为单次口服剂量给药。
250 mg CK-2017357 胶囊，单次口服给药。
其他名称：
500 mg CK-2017357 胶囊，单次口服。
其他名称：
|
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实验性的：Treatment Sequence 2
Treatment sequence 2 consisted of three dosing periods in which patients received single oral doses of placebo, 500 mg, and 250 mg of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
胶囊中的匹配安慰剂作为单次口服剂量给药。
250 mg CK-2017357 胶囊，单次口服给药。
其他名称：
500 mg CK-2017357 胶囊，单次口服。
其他名称：
|
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实验性的：Treatment Sequence 3
Treatment sequence 3 consisted of three dosing periods in which patients received single oral doses of 250 mg, placebo and 500 mg of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
胶囊中的匹配安慰剂作为单次口服剂量给药。
250 mg CK-2017357 胶囊，单次口服给药。
其他名称：
500 mg CK-2017357 胶囊，单次口服。
其他名称：
|
|
实验性的：Treatment Sequence 4
Treatment sequence 4 consisted of three dosing periods in which patients received single oral doses of 250 mg, 500 mg and placebo of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
胶囊中的匹配安慰剂作为单次口服剂量给药。
250 mg CK-2017357 胶囊，单次口服给药。
其他名称：
500 mg CK-2017357 胶囊，单次口服。
其他名称：
|
|
实验性的：Treatment Sequence 5
Treatment sequence 5 consisted of three dosing periods in which patients received single oral doses of 500 mg, placebo, and 250 mg of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
胶囊中的匹配安慰剂作为单次口服剂量给药。
250 mg CK-2017357 胶囊，单次口服给药。
其他名称：
500 mg CK-2017357 胶囊，单次口服。
其他名称：
|
|
实验性的：Treatment Sequence 6
Treatment sequence6 consisted of three dosing periods in which patients received single oral doses of 500 mg, 250 mg, and placebo of CK-2017357, in that order, with approximately one week between each dose.
Each patient acted as their own control, as all doses were represented in each treatment sequence.
|
胶囊中的匹配安慰剂作为单次口服剂量给药。
250 mg CK-2017357 胶囊，单次口服给药。
其他名称：
500 mg CK-2017357 胶囊，单次口服。
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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ALSFRS-R
大体时间：2 days
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An instrument for evaluating the functional status of patients with ALS.
Minimum score is 0 and maximum score is 40.
The higher the score the more function is retained.
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2 days
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Maximum grip strength
大体时间：2 days
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Measured using the DynEx Electronic Hand Dynamometer.
Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction.
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2 days
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Maximum grip strength fatigability
大体时间：2 days
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Handgrip fatigue is measured using the DynEx Electronic Hand Dynamometer.
Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds.
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2 days
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Shoulder extension fatigue
大体时间：2 days
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Patient is asked to hold one arm outstretched in front of them at a 90 degree angle.
The time the arm falls below 90 degrees for > 2 seconds will be recorded, up to a total evaluation time of 2 minutes.
This is then repeated with the other arm.
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2 days
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Slow Vital Capacity (SVC)
大体时间：2 days
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SVC is measured using the Puritan Bennett Renaissance II Spirometry System and accessories.
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2 days
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Maximum Voluntary Ventilation (MVV)
大体时间：2 days
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MVV is the volume of air that can be exhaled during 12 seconds of rapid deep breathing.
The actual volume is extrapolated to one minute.
the Puritan Bennett Renaissance II Spirometry System and accessories is used for this measurement.
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2 days
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Sniff Inspiratory Pressure (SNIP)
大体时间：2 days
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SNIP is measured at Functional Residual Capacity, the bottom of the tidal breathing cycle, through one plugged nostril while the other remains open using the Micro Medical MicroRPM Respiratory Pressure Meter
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2 days
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Maximum Voluntary Muscle Contraction (MVC)
大体时间：2 days
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MVC is measured using the MicroFET 2 HHD.
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2 days
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Repeated Sub-Maximum Grip Strength Fatigability
大体时间：2 days
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Sub-Maximum Grip Strength Fatigability is measured using the DynEx Electronic Hand.
Dynamometer
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2 days
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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发生不良事件的患者人数
大体时间：4周
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4周
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and ALSFRS-R.
大体时间：2 days
|
ALSFRS-R assessments will be paired with PK concentrations obtained at or near the same time as the ALSFRS-R assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength
大体时间：2 days
|
Maximum grip strength assessments will be paired with PK concentrations obtained at or near the same time as the maximum grip strength assessments and analyzed for concentration related effects.
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2 days
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum grip strength fatigability
大体时间：2 days
|
Maximum grip strength fatigability assessments will be paired with PK concentrations obtained at or near the same time as the maximum grip strength fatigability assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and shoulder extension fatigue
大体时间：2 days
|
Shoulder extension fatigue assessments will be paired with PK concentrations obtained at or near the same time as the shoulder extension fatigue assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and slow vital capacity
大体时间：2 days
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Slow vital capacity assessments will be paired with PK concentrations obtained at or near the same time as the slow vital capacity assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary ventilation
大体时间：2 days
|
Maximum voluntary ventilation assessments will be paired with PK concentrations obtained at or near the same time as the maximum voluntary ventilation assessments and analyzed for concentration related effects.
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2 days
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and sniff inspiratory pressure
大体时间：2 days
|
Sniff inspiratory pressure assessments will be paired with PK concentrations obtained at or near the same time as the sniff inspiratory pressure assessments and analyzed for concentration related effects.
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2 days
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and maximum voluntary muscle contraction
大体时间：2 days
|
Maximum voluntary muscle contraction assessments will be paired with PK concentrations obtained at or near the same time as the maximum voluntary muscle contraction assessments and analyzed for concentration related effects.
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2 days
|
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Characterize the relationship, if any, between the plasma concentration of CK-2017357 and repeated sub-maximum grip strength fatigability
大体时间：2 days
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Repeated sub-maximum grip strength fatigability assessments will be paired with PK concentrations obtained at or near the same time as the repeated sub-maximum grip strength fatigability assessments and analyzed for concentration related effects.
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2 days
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Effect of CK-2017357 on patient determined global functional assessment
大体时间：2 days
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Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt pre-dose
|
2 days
|
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Effect of CK-2017357 on investigator determined global functional assessment
大体时间：2 days
|
Investigator will assess whether they the patient appears the same, better or worse as compared to the patient's status at pre-dose
|
2 days
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
赞助
调查人员
- 学习椅：Jeremy M Shefner, MD, PhD、State University of New York - Upstate Medical University
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2010年3月1日
初级完成 (实际的)
2010年11月1日
研究完成 (实际的)
2010年11月1日
研究注册日期
首次提交
2010年3月16日
首先提交符合 QC 标准的
2010年3月17日
首次发布 (估计)
2010年3月18日
研究记录更新
最后更新发布 (实际的)
2019年5月10日
上次提交的符合 QC 标准的更新
2019年5月7日
最后验证
2019年5月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.