A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS) - Full Text View

Purpose

The study will generate data on safety and tolerability after multiple daily doses of CK-2017357 in patients with ALS. Patients will be randomized into one of four different treatment groups, receiving daily oral doses of either placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days.

Condition	Intervention	Phase
Amyotrophic Lateral Sclerosis	Drug: Placebo Drug: CK-2017357	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effects of Multiple Doses 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:

Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
Safety and tolerability of CK-2017357 after multiple oral doses to steady state in patients with ALS

Secondary Outcome Measures:

ALSFRS-R [ Time Frame: 21 days ] [ Designated as safety issue: No ]
Measurement of muscle fatigue [ Time Frame: 21 days ] [ Designated as safety issue: No ]
Measurement of pulmonary function [ Time Frame: 21 days ] [ Designated as safety issue: No ]
Patient global assessment [ Time Frame: 21 days ] [ Designated as safety issue: No ]
Investigator global assessment [ Time Frame: 21 days ] [ Designated as safety issue: No ]


Enrollment:	50
Study Start Date:	June 2011
Study Completion Date:	March 2012
Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Matching Placebo	Drug: Placebo Three matching placebo tablets once daily for 14 days (Part A) or three matching placebo tablets once daily for 14 days taken concurrently with 50 mg riluzole (Part B)
Experimental: Active Drug Low Dose	Drug: CK-2017357 One 125 mg CK-2017357 tablet and two matching placebo tablets once daily for 14 days (Part A) or one 125 mg CK-2017357 tablet and two matching placebo tablets once daily for 14 days taken concurrently with 50 mg riluzole (Part B) Other Name: tirasemtiv
Experimental: Active Drug Mid Dose	Drug: CK-2017357 Two 125 mg CK-2017357 tablets and one matching placebo tablet once daily for 14 days (Part A) or two 125 mg CK-2017357 tablets and one matching placebo tablet once daily for 14 days taken concurrently with 50 mg riluzole (Part B)
Experimental: Active Drug High Dose	Drug: CK-2017357 Three 125 mg CK-2017357 tablets once daily for 14 days (Part A) or three 125 mg CK-2017357 tablets once daily for 14 days taken concurrently with 50 mg riluzole (Part B)

Detailed Description:

In Part A, approximately 24 patients will be randomized to one of four different treatment groups. After a 7-day washout of riluzole, patients in each treatment group will receive daily oral doses of placebo, 125 mg, 250 mg, or 375 mg of CK-2017357 for 14 days. Patients will take daily doses of CK-2017357 or placebo (Day 1 through Day 14) and will return to the study site on Day 2, Day 8 and Day 15. All patients will return for a follow-up visit 7 days (± 2 days) after their last dose.

In Part B, approximately 24 patients will be randomized to one of four different treatment groups as in Part A. Patients in Part B will be required to decrease their riluzole dose to 50 mg once a day (QD) for 7 days prior to randomization. After this 7 day period, patients will take riluzole at 50 mg QD concurrently with their morning dose of blinded study drug.

Eligibility


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

Criteria

Key Inclusion Criteria:

Able to comprehend and willing to sign an Informed Consent Form (ICF)
Males or females 18 years of age or older
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)
Maximum voluntary grip strength in at least one hand between 10 & 40 pounds (females) and 10 & 60 pounds (males)
Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
Able to swallow tablets with water
Willing and able to remain off riluzole for 4 weeks (Part A only)
Currently taking and tolerating a stable dose of 50 mg BID riluzole (Part B only)
Willing and able to reduce daily dose of riluzole to 50 mg for 4 weeks (Part B only)
Willing and able to refrain from caffeine-containing products during study participation
Willing and able to remain off warfarin and theophylline-containing medications during study participation
Has a caregiver who is capable of observing and reporting patient status, and also assisting in the proper use of nocturnal oximetry equipment
Able to perform pulmonary function tests

Key Exclusion Criteria:

Life expectancy <3 months
Participation in any trial in which receipt of investigational study drug occurred within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
Any prior treatment with CK-2017357
Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night

Other protocol-defined inclusion/exclusion criteria may apply.

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: NCT01378676

Locations


United States, California
California Pacific Medical Center
San Francisco, California, United States, 94115
United States, Florida
Mayo Florida
Jacksonville, Florida, United States, 32224
United States, Kansas
University of Kansas
Kansas City, Kansas, United States, 06053
United States, Maryland
Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
SUNY Upstate Medical Center
Syracuse, New York, United States, 13210
United States, North Carolina
Carolinas Neuromuscular ALS-MND Center
Charlotte, North Carolina, United States, 28207
United States, Pennsylvania
Penn State Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19107

Sponsors and Collaborators

Cytokinetics

Investigators


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

More Information


Responsible Party:	Cytokinetics
ClinicalTrials.gov Identifier:	NCT01378676 History of Changes
Other Study ID Numbers:	CY 4024
Study First Received:	June 20, 2011
Last Updated:	September 16, 2013
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