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

Condition(s) targeted: Amyotrophic Lateral Sclerosis

Intervention: Placebo (Drug); CK-2017357 (Drug); CK-2017357 (Drug); CK-2017357 (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Cytokinetics

Official(s) and/or principal investigator(s):
Jeremy Shefner, MD, PhD, Study Chair, Affiliation: State University of New York - Upstate Medical University

Overall contact:
Jean Masonek, Email: jmasonek@cytokinetics.com

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.

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)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Number of Participants with Adverse Events as a Measure of Safety and Tolerability

Secondary outcome:

ALSFRS-R

Measurement of muscle fatigue

Measurement of pulmonary function

Patient global assessment

Investigator global assessment

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

6. Able to swallow tablets with water

7. Willing and able to remain off riluzole for 4 weeks (Part A only)

8. Currently taking and tolerating a stable dose of 50 mg BID riluzole (Part B only)

9. Willing and able to reduce daily dose of riluzole to 50 mg for 4 weeks (Part B only)

10. Willing and able to refrain from caffeine-containing products during study participation

11. Willing and able to remain off warfarin and theophylline-containing medications during study participation

12. Has a caregiver who is capable of observing and reporting patient status, and also assisting in the proper use of nocturnal oximetry equipment

13. Able to perform pulmonary function tests

Key Exclusion Criteria:

1. Life expectancy <3 months

2. 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

3. Any prior treatment with CK-2017357

4. Use of non-invasive positive pressure ventilation (NIPPV) for any part of the day or night

Other protocol-defined inclusion/exclusion criteria may apply.

Jean Masonek, Email: jmasonek@cytokinetics.com

California Pacific Medical Center, San Francisco, California 94115, United States; Recruiting

Mayo Florida, Jacksonville, Florida 32224, United States; Recruiting

University of Kansas, Kansas City, Kansas 06053, United States; Recruiting

Johns Hopkins Hospital, Baltimore, Maryland 21287, United States; Recruiting

Columbia University Medical Center, New York, New York 10032, United States; Recruiting

SUNY Upstate Medical Center, Syracuse, New York 13210, United States; Recruiting

Carolinas Neuromuscular ALS-MND Center, Charlotte, North Carolina 28207, United States; Recruiting

Penn State Hershey Medical Center, Hershey, Pennsylvania 17033, United States; Recruiting

Drexel University College of Medicine, Philadelphia, Pennsylvania 19107, United States; Recruiting

Starting date: June 2011
Last updated: October 28, 2011