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

Purpose

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	Intervention	Phase
Amyotrophic Lateral Sclerosis	Drug: Placebo Drug: 250 mg CK-2017357 Drug: 500 mg CK-2017357	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:

Genetics Home Reference related topics: amyotrophic lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis

Genetic and Rare Diseases Information Center resources: Amyotrophic Lateral Sclerosis

U.S. FDA Resources

Further study details as provided by Cytokinetics:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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:

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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: Yes ]
To evaluate the effect of CK-2017357 on patient and investigator determined global functional assessment [ Time Frame: 2 days ] [ Designated as safety issue: No ]


Enrollment:	67
Study Start Date:	March 2010
Study Completion Date:	November 2010
Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01089010

Locations


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

Cytokinetics

Investigators


Study Chair:	Jeremy M Shefner, MD, PhD	State University of New York - Upstate Medical University

More Information


Responsible Party:	Andrew Wolff, MD, FACC, Chief Medical Officer, Cytokinetics, Inc.
ClinicalTrials.gov Identifier:	NCT01089010 History of Changes
Other Study ID Numbers:	CY 4021
Study First Received:	March 16, 2010
Last Updated:	May 11, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


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

ClinicalTrials.gov processed this record on September 26, 2016