Dose Titration Study to Test Safety and Effects of CK-2017357 in Patients With Amyotrophic Lateral Sclerosis (ALS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cytokinetics
ClinicalTrials.gov Identifier:
NCT01486849
First received: November 23, 2011
Last updated: September 16, 2013
Last verified: March 2012
  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).


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

Resource links provided by NLM:


Further study details as provided by Cytokinetics:

Primary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: approximately 29 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Change from baseline in score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Change from baseline in scores on tests of muscle fatigue (handgrip fatigue, muscle strength, and timed up and go test) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Change from baseline in scores on tests of pulmonary function (Sniff Nasal Inspiratory Pressure [SNIP], Slow Vital Capacity [SVC] and Maximum Voluntary Ventilation [MVV]) [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Change from baseline in patient global assessment [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Change from baseline in investigator global assessment [ Time Frame: 21 days ] [ Designated as safety issue: No ]
  • Evaluate the pharmacokinetics of CK-2017357 [ Time Frame: Day 1, Day 15, and Day 22 ] [ Designated as safety issue: No ]
  • Evaluate the pharmacokinetics of riluzole in patients receiving CK-2017357 [ Time Frame: Day 1, Day 15, and Day 22 ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: November 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Titration of CK-2017357 (Group 1)
Dose titration of active drug as add-on therapy to riluzole
Drug: CK-2017357
Total daily oral dose of 250 mg (125 mg BID) of CK-2017357 for 7 days followed by total daily oral dose of 375 mg (125 mg AM and 250 mg PM) for 7 days followed by total daily oral dose of 500 mg (250 mg BID) of CK-2017357 for 7 days
Other Name: tirasemtiv
Placebo Comparator: Matching Placebo (Group 2)
Placebo as add-on therapy to riluzole
Drug: Placebo
Matching placebo tablets BID for 21 days

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  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: NCT01486849

Locations
United States, California
University of California at San Francisco, Fresno Campus, Central California Neurological Institute
Fresno, California, United States, 93701
Coordinated Clinical Research
La Jolla, California, United States, 92037
University of California at Irvine, ALS and Neuromuscular Center
Orange, California, United States, 92868
United States, Connecticut
Hospital for Special Care
New Britain, Connecticut, United States, 06053
United States, Massachusetts
Massachusetts General Hospital, Neurology Clinical Trials Unit
Charlestown, Massachusetts, United States, 02129
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
Cornell Faculty, Hospital for Special Surgery
New York, New York, United States, 10021
United States, North Carolina
Duke University School of Medicine, Division of Neurology
Durham, North Carolina, United States, 27710
United States, Ohio
Ohio State University, Department of Neurology
Columbus, Ohio, United States, 43210
United States, Oregon
Providence ALS Center
Portland, Oregon, United States, 97213
United States, Texas
University of Texas Health Science Center, Department of Neurology
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Cytokinetics
Investigators
Study Chair: Jeremy Shefner, MD, PhD State University of New York - Upstate Medical University
  More Information

No publications provided

Responsible Party: Cytokinetics
ClinicalTrials.gov Identifier: NCT01486849     History of Changes
Other Study ID Numbers: CY 4025
Study First Received: November 23, 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 22, 2014