A Phase II, Multicenter, Double-Blind, Randomized, Placebo-Controlled Dose Titration Study to Evaluate the Safety, Tolerability and Pharmacodynamic Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

Study Purpose:

A Phase II, double-blind, randomized, placebo-controlled ascending dose titration study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamic effects of multiple ascending doses of CK-2017357 to an individual patient maximum tolerated dose (MTD), using a within-patient twice daily (BID) dose-titration regimen in ALS patients on 50 mg riluzole once daily (QD).

Study Status:

Not recruiting


Amyotrophic Lateral Sclerosis

Study Type:


Type of Intervention:


Intervention Name:

CK-2017357, Placebo, Riluzole 50 MG



Phase 2

Study Chair(s)/Principal Investigator(s):

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

Clinicaltrials.gov ID:


Neals Affiliated?


Coordinating Center Contact Information


California, United States

Full Study Summary:

Patients will be randomized to one of two dosing groups, active CK-2017357 or placebo, in a 3:1 ratio. Prior to study drug dosing, patients will be required to decrease their riluzole dose to 50 mg QD for 7 days; after this 7 day period patients will either receive placebo or start the titration on active CK-2017357 while continuing to take riluzole at 50 mg QD.

Potential patients will be screened to assess their eligibility to enter the study within 21 days prior to Day -7, when they will begin taking riluzole at the decreased dose of 50 mg QD. Patients will be randomized in a 3:1 ratio to CK-2017357 (Group 1) or placebo (Group 2). On Day 1, patients will begin taking a total daily dose of 250 mg (125 mg BID) of CK-2017357 or matching placebo tablets BID for 7 days. Then they will take a total daily dose of 375 mg (125 mg morning [AM] and 250 mg evening [PM]) of CK-2017357 or matching placebo tablets BID for 7 days, and finally, they will take a total daily dose of 500 mg (250 mg BID) of CK-2017357 or matching placebo tablets BID for 7 days. A final dose of 250 mg of CK-2017357 or placebo will be taken in the morning on Day 22 at the study site.

Dose-escalation of CK-2017357 or placebo may be stopped, or the dose reduced to a lower level, based on tolerability. All patients who return to a lower dose will stay on that dose for the remainder of the study.

Patients will remain on the decreased dose of riluzole until the follow-up visit approximately 7 days after Day 22.

Study Sponsor:


Participant Duration:

21 days on treatment, 29 days total

Estimated Enrollment:


Estimated Study Start Date:

10 / 31 / 2011

Estimated Study Completion Date:

03 / 01 / 2012

Posting Last Modified Date:

05 / 03 / 2019

Date Study Added to neals.org:

12 / 07 / 2011

Minimum Age:

18 Years

Maximum Age:


Inclusion Criteria:

1. Able to comprehend and willing to sign an Informed Consent Form (ICF)

2. Males or females 18 years of age or older

3. 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)

4. Maximum voluntary grip strength in at least one hand between 10 & 40 pounds (females) and 10 & 60 pounds (males)

5. Able to swallow tablets with water

6. Currently taking and tolerating a stable dose of 50 mg BID riluzole

7. Willing and able to reduce daily dose of riluzole to 50mg QD for 5 weeks

8. Not currently taking or willing and able to remain off theophylline-containing medications during study participation

9. Patient has a caregiver who is capable of observing and reporting patient status

10. Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex

11. Able to perform pulmonary function tests

Exclusion Criteria:

1. Life expectancy <3 months

2. Receipt of investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing

3. Any prior treatment with CK-2017357

4. Any use of non-invasive positive pressure ventilation (NIPPV), such as Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP)

Other protocol-defined inclusion/exclusion criteria may apply.

University of California at San Francisco, Fresno Campus, Central California Neurological Institute

Fresno, California 93701
United States

Coordinated Clinical Research

La Jolla, California 92037
United States

University of California at Irvine, ALS and Neuromuscular Center

Orange, California 92868
United States

Hospital for Special Care

New Britain, Connecticut 06053
United States

Massachusetts General Hospital, Neurology Clinical Trials Unit

Charlestown, Massachusetts 02129
United States

Washington University

Saint Louis, Missouri 63110
United States

Cornell Faculty, Hospital for Special Surgery

New York, New York 10021
United States

Duke University School of Medicine, Division of Neurology

Durham, North Carolina 27710
United States

Ohio State University, Department of Neurology

Columbus, Ohio 43210
United States

Providence ALS Center

Portland, Oregon 97213
United States

University of Texas Health Science Center, Department of Neurology

San Antonio, Texas 78229
United States