A Study of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01089010
Recruitment Status : Completed
First Posted : March 18, 2010
Last Update Posted : May 13, 2011
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Placebo Drug: 250 mg CK-2017357 Drug: 500 mg CK-2017357 Phase 2

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : March 2010
Actual Primary Completion Date : November 2010
Actual Study Completion Date : November 2010

Arm Intervention/treatment
Experimental: Three-way crossover
2 oral dose levels of CK-2017357 and placebo
Drug: Placebo
Matching placebo in capsules administered as a single oral dose.

Drug: 250 mg CK-2017357
250 mg CK-2017357 in capsules administered as a single oral dose.

Drug: 500 mg CK-2017357
500 mg CK-2017357 in capsules administered as a single oral dose.

Primary Outcome Measures :
  1. 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. [ Time Frame: 2 days ]

    In this hypothesis-generating early Phase II study, multiple assessments of skeletal muscle function will be made without specifying a single primary endpoint, including:

    1. ALS Functional Assessment
    2. Maximum Grip Strength (bilateral)
    3. Maximum Grip Strength Fatigability (bilateral)
    4. Shoulder Extension Fatigue (bilateral)
    5. Slow Vital Capacity
    6. Maximal Voluntary Ventilation
    7. Sniff Inspiratory Pressure
    8. Maximum Voluntary Muscle Contraction of multiple bilateral muscle groups using Hand Held Dynamometry
    9. Repeated Sub-Maximum Grip Strength Fatigability (bilateral)

Secondary Outcome Measures :
  1. To evaluate and characterize the relationship, if any, between the plasma concentration of CK-2017357 and its pharmacodynamic effects (PK/PD relationship) [ Time Frame: 2 day ]
  2. To evaluate the safety and tolerability of 2 doses of CK-2017357 given as single doses administered orally to patients with ALS [ Time Frame: 4 weeks ]
  3. To evaluate the effect of CK-2017357 on patient and investigator determined global functional assessment [ Time Frame: 2 days ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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, 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 between 10 & 40 pounds (females) and 10 & 60 pounds (males)
  • Able to maintain grip contraction for 15 seconds
  • Upright Slow Vital Capacity (SVC) ≥40% of predicted for age, height, and sex
  • Able to perform pulmonary function tests
  • Pre-study clinical laboratory findings (including troponin I (TnI) and 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 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:

  • Significant hepatic/renal insufficiency as defined by Upper Limit of Normal (ULN) laboratory findings
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01089010

United States, Arizona
Phoenix Neurological Associates, Ltd.
Phoenix, Arizona, United States, 85018
United States, California
University Neurology Associates
Fresno, California, United States, 93701
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Florida
Mayo Clinic Florida
Jacksonville, Florida, United States, 32224
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
SUNY Upstate Medical Center
Syracuse, New York, United States, 13210
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
United States, Oregon
Providence ALS Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
Drexel University College of Medicine, Dept of Neurology
Philadelphia, Pennsylvania, United States, 19102
Penn State
University Park, Pennsylvania, United States, 17033
United States, Texas
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
Study Chair: Jeremy M Shefner, MD, PhD State University of New York - Upstate Medical University

Responsible Party: Andrew Wolff, MD, FACC, Chief Medical Officer, Cytokinetics, Inc. Identifier: NCT01089010     History of Changes
Other Study ID Numbers: CY 4021
First Posted: March 18, 2010    Key Record Dates
Last Update Posted: May 13, 2011
Last Verified: May 2011

Additional relevant MeSH terms:
Amyotrophic Lateral Sclerosis
Motor Neuron Disease
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases