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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 |
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Study Focus:
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). |
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Disease:
Amyotrophic Lateral Sclerosis (ALS), Sporadic ALS, Familial ALS |
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Study Category:
Drug Trial |
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Study Status:
Closed |
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Phase:
Phase II |
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Type:
Interventional Trial
with active agents/drugs & a placebo |
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Funding Source:
Cytokinetics |
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Study Chair(s)/Principal Investigator(s):
Jeremy Shefner, MD, PhD (State University of New York - Upstate Medical University) |
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Clinicaltrials.gov ID:
NCT01486849 |
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NEALS Affiliated?
No |
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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. |
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Participant Duration:
21 days on treatment, 29 days total |
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# of Subjects:
28 |
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Enrollment Start Date:
11/01/2011 |
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Posting Last Modified Date:
03/01/2012 |
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Date Study Added to alscortium.org:
12/07/2011 |
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| Eligibility Criteria |
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Gender:
Male & Female |
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Minimum Age:
18 |
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Min Vital Capacity (% predicted normal):
50% |
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Can participants use Riluzole?
Riluzole use required by protocol |
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Other Eligibility Criteria:
Inclusion Criteria:
Able to comprehend and willing to sign an Informed Consent Form (ICF)
Males or females 18 years of age or older
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)
Maximum voluntary grip strength in at least one hand between 10 & 40 pounds (females) and 10 & 60 pounds (males)
Able to swallow tablets with water
Currently taking and tolerating a stable dose of 50 mg BID riluzole
Willing and able to reduce daily dose of riluzole to 50mg QD for 5 weeks
Not currently taking or willing and able to remain off theophylline-containing medications during study participation
Patient has a caregiver who is capable of observing and reporting patient status
Upright Slow Vital Capacity (SVC) >50% of predicted for age, height, and sex
Able to perform pulmonary function tests
Exclusion Criteria:
Life expectancy less than 3 months
Receipt of investigational study drug within 30 days or 5 half-lives of the prior agent, whichever is greater, prior to dosing
Any prior treatment with CK-2017357
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. |
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Site Contact Information (Please click to show/hide) |
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| California |
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University of California at San Francisco, Fresno Campus,
Central California Neurological Institute
Fresno, California 93701
UNITED STATES |
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Coordinated Clinical Research
La Jolla, California 92037
UNITED STATES | |
University of California at Irvine, ALS and Neuromuscular Center
Orange, California 92868
UNITED STATES |
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| Connecticut |
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Hospital for Special Care
New Britain, Connecticut 06053
UNITED STATES |
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| Massachusetts |
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Massachusetts General Hospital
Neurology Clinical Trials Unit
Charlestown, Massachusetts 02129
UNITED STATES |
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| Missouri |
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Washington University
St. Louis, Missouri 63110
UNITED STATES |
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| New York |
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Cornell Faculty, Hospital for Special Surgery
New York, New York 10021
UNITED STATES |
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| North Carolina |
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Duke University School of Medicine
Division of Neurology
Durham, North Carolina 27710
UNITED STATES |
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| Ohio |
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Ohio State University
Department of Neurology
Columbus, Ohio 43210
UNITED STATES |
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| Oregon |
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Providence ALS Center
Portland, Oregon 97213
UNITED STATES |
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| Texas |
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University of Texas Health Science Center
Department of Neurology
San Antonio, Texas 78229
UNITED STATES |
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Familial ALS- ALS cases are inherited from 2 or more family members, affects 5-10% of ALS cases. Sporadic ALS- disease occurs at random with no clearly associated risk factors; most common form of ALS, affects approximately 90-95% ALS cases. Interventional trial- study where exposure, for example a drug, is assigned; used to determine the effectiveness of a treatment or intervention. With drugs and a placebo- One group gets the active treatment, the other gets the placebo. Everything else is held the same between the two groups, so that any difference in their outcome can be attributed to the active treatment. Observational study- study in which patients are observed and where no treatment is given; researcher has no control over the experiment because they are done in a more natural setting than an interventional trial. Trial Phase- objectives are different for each phase of a trial. - Phase I, drug is given to a small number of people to see if it is safe.
- Phase II begins to look at effectiveness of the drug.
- Phase III is considered the definitive test of whether a drug is effective, held at multiple research sites and much larger than the previous phases.
Vital Capacity- the maximum amount of air that can be expelled from the lungs after a maximum drawing of air into the lungs, measured by a spirometer and then scored as a percentage. |
