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A Study to Evaluate the Effects of Multiple Doses 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.
 
ClinicalTrials.gov Identifier: NCT01378676
Recruitment Status : Completed
First Posted : June 22, 2011
Last Update Posted : May 7, 2019
Sponsor:
Information provided by (Responsible Party):
Cytokinetics

Study Description
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Brief Summary:
The study will generate data on safety, tolerability and pharmacokinetics 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 or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: Placebo (Part A) Drug: CK-2017357 (Part A) Drug: Riluzole 50 MG (Part B) Drug: Placebo (Part B) Drug: CK-2017357 (Part B) Phase 2

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 additional 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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)
Study Start Date : June 2011
Actual Primary Completion Date : March 2012
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Matching Placebo Drug: Placebo (Part A)
Placebo tablets once daily for 14 days (Part A)

Drug: Riluzole 50 MG (Part B)
One 50 mg tablet once daily for 14 days (Part B)

Drug: Placebo (Part B)
Placebo tablets once daily for 14 days (Part B)
Experimental: Active Drug Low Dose (CK-2017357 125 mg) Drug: Placebo (Part A)
Placebo tablets once daily for 14 days (Part A)

Drug: CK-2017357 (Part A)
One 125 mg CK-2017357 tablet once daily for 14 days (Part A)
Other Name: tirasemtiv

Drug: Riluzole 50 MG (Part B)
One 50 mg tablet once daily for 14 days (Part B)

Drug: Placebo (Part B)
Placebo tablets once daily for 14 days (Part B)

Drug: CK-2017357 (Part B)
One 125 mg tablet once daily for 14 days (Part B)
Other Name: tirasemtiv
Experimental: Active Drug Mid Dose (CK-2017357 250 mg) Drug: Placebo (Part A)
Placebo tablets once daily for 14 days (Part A)

Drug: CK-2017357 (Part A)
Two 125 mg CK-2017357 tablets once daily for 14 days (Part A)
Other Name: tirasemtiv

Drug: Riluzole 50 MG (Part B)
One 50 mg tablet once daily for 14 days (Part B)

Drug: Placebo (Part B)
Placebo tablets once daily for 14 days (Part B)

Drug: CK-2017357 (Part B)
Two 125 mg tablets once daily for 14 days (Part B)
Other Name: tirasemtiv
Experimental: Active Drug High Dose (CK-2017357 375 mg) Drug: CK-2017357 (Part A)
Three 125 mg CK-2017357 tablets once daily for 14 days (Part A)
Other Name: tirasemtiv

Drug: Riluzole 50 MG (Part B)
One 50 mg tablet once daily for 14 days (Part B)

Drug: CK-2017357 (Part B)
Three 125 mg tablets once daily for 14 days (Part B)
Other Name: tirasemtiv


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 21 days ]
    Safety and tolerability of CK-2017357 after multiple oral doses to steady state in patients with ALS


Secondary Outcome Measures :
  1. Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: 21 days ]
    An instrument for evaluating the functional status of patients with ALS. Minimum score is 0 and maximum score is 40. The higher the score the more function is retained.

  2. Measurement of Grip Strength and Handgrip Fatigue [ Time Frame: 21 days ]
    Measured using the DynEx Electronic Hand Dynamometer. Patients asked to squeeze the device with the maximum possible force to establish the maximum voluntary contraction. Handgrip fatigue is then measured. Patient is asked to squeeze the device until they can no longer stay above 60% of target or 120 seconds.

  3. Measurement of muscle strength [ Time Frame: 21 days ]
    Muscle strength is measured using Hand Held Dynamometry. A series of assessments are done on different muscle groups.

  4. Measurement of Slow Vital Capacity (SVC) [ Time Frame: 21 days ]
    SVC will be measured using the ndd EasyOne Spirometer System at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit

  5. Measurement of Sniff Nasal Inspiratory Pressure (SNIP) [ Time Frame: 21 days ]
    SNIP will be measured using the Micro Medical Respiratory Pressure Meter (MicroRPM) at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit

  6. Measurement of Maximum Voluntary Ventilation (MVV) [ Time Frame: 21 days ]
    MVV will be measured using the EasyOne Spirometer System at Screening, Day -7, Day 1, Day 2, Day 8, Day 15 and at the Follow-Up Visit

  7. Patient global assessment [ Time Frame: 15 days ]
    Patients will be asked to assess whether they feel the same, better or worse as compared to how they felt at pre-dose on Day 1

  8. Investigator global assessment [ Time Frame: 15 days ]
    Investigator will assess whether the patient appears the same, better or worse as compared to the patient's status at pre-dose on Day 1.


Eligibility Criteria
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Information from the National Library of Medicine

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

Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT01378676


Locations
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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
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Study Chair: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
More Information
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Publications of Results:

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Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT01378676    
Other Study ID Numbers: CY 4024
First Posted: June 22, 2011    Key Record Dates
Last Update Posted: May 7, 2019
Last Verified: May 2019
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
 Metabolic Diseases
Riluzole
Anticonvulsants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents