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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

Tracking Information
First Submitted Date  ICMJE June 20, 2011
First Posted Date  ICMJE June 22, 2011
Last Update Posted Date May 7, 2019
Study Start Date  ICMJE June 2011
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2011)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01378676 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2019)
  • 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.
  • 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.
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2011)
  • ALSFRS-R [ Time Frame: 21 days ]
  • Measurement of muscle fatigue [ Time Frame: 21 days ]
  • Measurement of pulmonary function [ Time Frame: 21 days ]
  • Patient global assessment [ Time Frame: 21 days ]
  • Investigator global assessment [ Time Frame: 21 days ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Effects of Multiple Doses of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)
Official Title  ICMJE 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)
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • 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: CK-2017357 (Part A)
    Two 125 mg CK-2017357 tablets once daily for 14 days (Part A)
    Other Name: tirasemtiv
  • 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: 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
  • Drug: CK-2017357 (Part B)
    Two 125 mg tablets once daily for 14 days (Part B)
    Other Name: tirasemtiv
  • Drug: CK-2017357 (Part B)
    Three 125 mg tablets once daily for 14 days (Part B)
    Other Name: tirasemtiv
Study Arms  ICMJE
  • Placebo Comparator: Matching Placebo
    Interventions:
    • Drug: Placebo (Part A)
    • Drug: Riluzole 50 MG (Part B)
    • Drug: Placebo (Part B)
  • Experimental: Active Drug Low Dose (CK-2017357 125 mg)
    Interventions:
    • Drug: Placebo (Part A)
    • Drug: CK-2017357 (Part A)
    • Drug: Riluzole 50 MG (Part B)
    • Drug: Placebo (Part B)
    • Drug: CK-2017357 (Part B)
  • Experimental: Active Drug Mid Dose (CK-2017357 250 mg)
    Interventions:
    • Drug: Placebo (Part A)
    • Drug: CK-2017357 (Part A)
    • Drug: Riluzole 50 MG (Part B)
    • Drug: Placebo (Part B)
    • Drug: CK-2017357 (Part B)
  • Experimental: Active Drug High Dose (CK-2017357 375 mg)
    Interventions:
    • Drug: CK-2017357 (Part A)
    • Drug: Riluzole 50 MG (Part B)
    • Drug: CK-2017357 (Part B)
Publications * Shefner JM, Watson ML, Meng L, Wolff AA; Neals/Cytokinetics STUDY Team. A study to evaluate safety and tolerability of repeated doses of tirasemtiv in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener. 2013 Dec;14(7-8):574-81. doi: 10.3109/21678421.2013.822517. Epub 2013 Aug 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 26, 2019)
49
Original Estimated Enrollment  ICMJE
 (submitted: June 21, 2011)
24
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date March 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01378676
Other Study ID Numbers  ICMJE CY 4024
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cytokinetics
Study Sponsor  ICMJE Cytokinetics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
PRS Account Cytokinetics
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP