Study Purpose:
This study assessed the effect of tirasemtiv versus placebo on respiratory function in patients with ALS.Study Status:
Not recruiting
Disease:
Amyotrophic Lateral Sclerosis
Study Type:
Interventional
Type of Intervention:
Drug
Intervention Name:
Tirasemtiv, Placebo tablets
Placebo:
Phase:
Phase 3
Study Chair(s)/Principal Investigator(s):
MD, Cytokinetics
Clinicaltrials.gov ID:
Neals Affiliated?
Yes
Coordinating Center Contact Information
MD Cytokinetics
United States
Full Study Summary:
CY 4031 was a multi-national, double-blind, randomized, placebo-controlled, stratified, parallel group study of tirasemtiv in patients with ALS. The study had three phases: an open-label phase (2 weeks), a double-blind, placebo-controlled phase (48 weeks), and a double-blind, placebo-controlled tirasemtiv withdrawal phase (4 weeks). Patients who completed 2 weeks of treatment with open-label tirasemtiv (125 mg twice daily) were randomized 3:2:2:2 to placebo or one of three dose levels of tirasemtiv (250 mg/day, 375 mg/day, or 500 mg/day). Approximately 600 patients were planned to be enrolled into the open-label treatment phase.
Patients taking riluzole at study entry could continue use of riluzole during the study as long as they had been on a stable dose for at least 30 days prior to study screening. In addition, for patients randomized to tirasemtiv, the riluzole dose was reduced to half the approved dose (ie, reduced to 50 mg once daily) because administration of tirasemtiv approximately doubles the exposure to concomitant riluzole. Patients randomized to placebo continued riluzole at 50 mg twice daily. This was accomplished without unmasking the study's blind as follows:
1. All patients on riluzole took their morning 50 mg dose of riluzole from their personal riluzole supply.
2. The sponsor supplied the evening riluzole dose as double-blind study medication, as follows: (a) for patients randomized to placebo, the double-blind, evening riluzole dose was 50 mg of active riluzole; (b) for patients randomized to tirasemtiv, the double-blind, evening riluzole dose was a matching placebo for riluzole.
Patients taking riluzole at study entry could continue use of riluzole during the study as long as they had been on a stable dose for at least 30 days prior to study screening. In addition, for patients randomized to tirasemtiv, the riluzole dose was reduced to half the approved dose (ie, reduced to 50 mg once daily) because administration of tirasemtiv approximately doubles the exposure to concomitant riluzole. Patients randomized to placebo continued riluzole at 50 mg twice daily. This was accomplished without unmasking the study's blind as follows:
1. All patients on riluzole took their morning 50 mg dose of riluzole from their personal riluzole supply.
2. The sponsor supplied the evening riluzole dose as double-blind study medication, as follows: (a) for patients randomized to placebo, the double-blind, evening riluzole dose was 50 mg of active riluzole; (b) for patients randomized to tirasemtiv, the double-blind, evening riluzole dose was a matching placebo for riluzole.
Study Sponsor:
Cytokinetics
Estimated Enrollment:
744
Estimated Study Start Date:
09 / 03 / 2015
Estimated Study Completion Date:
09 / 27 / 2017
Posting Last Modified Date:
09 / 09 / 2020
Date Study Added to neals.org:
07 / 14 / 2015
Minimum Age:
18 Years
Maximum Age:
N/A
Can participants use Riluzole?
Yes
Inclusion Criteria:- 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) ≤ 24 months prior to screening
- Upright SVC ≥ 70 % of predicted for age, height and sex
- Able to swallow tablets without crushing, and in the opinion of the Investigator, is expected to continue to be able to do so during the trial
- A caregiver if one is needed
- Clinical laboratory findings within the normal range or, if outside the normal range, deemed not clinically significant by the Investigator
- Male patients must agree for the duration of the study and 10 weeks after the end of the study to use a condom during sexual intercourse with female partners who are of childbearing potential (i.e., following menarche until post-menopausal if not anatomically and physiologically incapable of becoming pregnant) and to have female partners use an additional effective means of contraception (e.g., diaphragm plus spermicide, or oral contraceptives) or the male patient must agree to abstain from sexual intercourse during and for 10 weeks after the end of the study, unless the male patient has had a vasectomy and confirmed sperm count is zero
- Female patients must be post-menopausal (≥ 1 year) or sterilized, or, if of childbearing potential, not be breastfeeding, have a negative pregnancy test, have no intention to become pregnant during the course of the study, and use effective contraceptive drugs or devices while requiring male partner to use a condom for the duration of the study and for 10 weeks after the end of the study
- Patients must be either on a stable dose of riluzole 50 mg twice daily for at least 30 days prior to screening or have not taken riluzole for at least 30 days prior to screening and are willing not to begin riluzole use until they complete study drug dosing
Exclusion Criteria:
- At the time of screening, any use of non-invasive positive pressure ventilation (NIPPV, e.g. continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BiPAP]) for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation
- Patients with a diaphragm pacing system (DPS) at study entry or who anticipate DPS placement during the course of the study
- BMI of 20.0 kg/m2 or lower
- Unwilling or unable to discontinue tizanidine and theophylline-containing medications during study participation
- Serum chloride outside the normal reference range
- Neurological impairment due to a condition other than ALS, including history of transient ischemic attack within the past year
- Presence at screening of any medically significant cardiac, pulmonary, GI, musculoskeletal, or psychiatric illness that might interfere with the patient's ability to comply with study procedures or that might confound the interpretation of clinical safety or efficacy data, including, but not limited to:
1. Poorly controlled hypertension
2. NYHA Class II or greater congestive heart failure
3. Chronic obstructive pulmonary disease or asthma requiring daily use bronchodilator medications
4. GI disorder that might impair absorption of study drug
5. History of significant liver disease defined by bilirubin > 2 times the upper limit of normal (ULN) or ALT or AST > 3 times the ULN on repeat testing
6. Poorly controlled diabetes mellitus
7. History of vertigo within three months of study entry
8. History of syncope without an explainable or treated cause
9. History of untreated intracranial aneurysm or poorly controlled seizure disorder
10. Amputation of a limb
11. Cognitive impairment, related to ALS or otherwise, sufficient to impair the patient's ability to give informed consent and to understand and/or comply with study procedures
12. Cancer with metastatic potential (other than basal cell carcinoma, carcinoma in situ of the cervix, or squamous cell carcinoma of the skin excised with clean margins) diagnosed and treated within the last two years
13. Any other condition, impairment or social circumstance that, in the opinion of the Investigator, would render the patient not suitable to participate in the study
14. Patient judged to be actively suicidal or a suicide risk by the Investigator
- Has taken any investigational study drug within 30 days or five half-lives of the prior agent, whichever is greater, prior to dosing
- Prior participation in any form of stem cell therapy for the treatment of ALS
- Previously received tirasemtiv in any previous clinical trial
St. Joseph's Hospital & Medical Center - Barrow Neurology Clinics
Phoenix, Arizona
85013
United States
University of California San Diego
La Jolla, California
92093
United States
Cedars-Sinai Medical Center
Los Angeles, California
90048
United States
University of California, Irvine
Orange, California
92868
United States
University of California Davis Medical Center
Sacramento, California
95817
United States
Forbes Norris MDA/ALS Research Center
San Francisco, California
94115
United States
Stanford Hospital and Clinics
Stanford, California
94305
United States
University of Colorado Hospital Anschutz Outpatient Pavilion
Aurora, Colorado
80045
United States
Hospital for Special Care
New Britain, Connecticut
06053
United States
George Washington University Medical Center
Washington, District of Columbia
20037
United States
Mayo Clinic
Jacksonville, Florida
32224
United States
University of Miami
Miami, Florida
33136
United States
Carol and Frank Morsini Center for Advanced Health Care - University of South Florida
Tampa, Florida
33612
United States
The Emory Clinic
Atlanta, Georgia
30322
United States
Georgia Regents University
Augusta, Georgia
30912
United States
Northwestern University Feinberg School of Medicine
Chicago, Illinois
60611
United States
Indiana University
Indianapolis, Indiana
46202
United States
University of Iowa Hospitals and Clinics
Iowa City, Iowa
52242
United States
University of Kansas Medical Center
Kansas City, Kansas
66160
United States
Johns Hopkins University
Baltimore, Maryland
21287
United States
Massachusetts General Hospital
Boston, Massachusetts
02114
United States
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts
01655
United States
University of Michigan Hospital and Health System
Ann Arbor, Michigan
48109
United States
Henry Ford Health System
Detroit, Michigan
48202
United States
Hennepin County Medical Center
Minneapolis, Minnesota
55415
United States
Saint Louis University
Saint Louis, Missouri
63104
United States
Barnes-Jewish Hospital
Saint Louis, Missouri
63110
United States
Neurology Associates
Lincoln, Nebraska
68506
United States
Dartmouth Hitchcock Medical Center Dept of Neurology
Lebanon, New Hampshire
03756
United States
Hospital for Special Surgery
New York, New York
10021
United States
Neurological Institute Columbia University Medical Center
New York, New York
10032
United States
SUNY Upstate Medical University
Syracuse, New York
13210
United States
Neurosciences Institute: Neurology - Charlotte
Charlotte, North Carolina
28207
United States
Duke Neurological Disorders Clinic
Durham, North Carolina
27705
United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina
27157
United States
The Ohio State University Wexner Medical Center
Columbus, Ohio
43221
United States
Providence Brain and Spine Institute ALS Center
Portland, Oregon
97213
United States
Oregon Health and Science Center
Portland, Oregon
97239
United States
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania
17033
United States
The Penn Comprehensive Neuroscience Center
Philadelphia, Pennsylvania
19107
United States
Temple University School of Medicine
Philadelphia, Pennsylvania
19140
United States
Vanderbilt University Medical Center
Nashville, Tennessee
37232
United States
Texas Neurology
Dallas, Texas
75214
United States
Baylor College of Medicine
Houston, Texas
77030
United States
University of Texas Health Science Center
San Antonio, Texas
78229
United States
University of Virgina Health System
Charlottesville, Virginia
22908
United States
University of Washington Medical Center
Seattle, Washington
98195
United States
West Virginia University Department of Neurology
Morgantown, West Virginia
26506
United States
Froedtert Memorial Lutheran Hospital, Department of Neurology
Milwaukee, Wisconsin
53226
United States
UZ Leuven - Campus Gasthuisberg
Leuven, Vlaams Brabant
3000
Belgium
University of Calgary
Calgary, Alberta
T3M 1M4
Canada
Edmonton Kaye Clinic
Edmonton, Alberta
T6G 1Z1
Canada
Stan Cassidy Centre for Rehabilitation
Fredericton, New Brunswick
E3B OC7
Canada
QE II Health Sciences Centre, NHI Site
Halifax, Nova Scotia
B3H 1V7
Canada
McMaster University Medical Centre
Hamilton, Ontario
L8N 4K1
Canada
London Health Sciences Centre
London, Ontario
N6A 5A5
Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario
M4N 3M5
Canada
Notre-Dame Hospital/CHUM
Montreal, Quebec
H2L 4M1
Canada
Montreal Neurological Institute and Hospital
Montreal, Quebec
H3A 2B4
Canada
CHU de Quebec - Universite Laval Hopital de l'Enfant-Jesus
Quebec G1J 1Z4
Canada
Hopital R. Salengro, CHRU Lille
Lille Cedex 59037
France
CHU Dupuytren
Limoges cedex 87042
France
Hopital de la Timone
Marseille 13005
France
Hopital Gui de Chauliac
Montpellier 34295
France
CHU de Nice - Hopital Pasteur 2
Nice Cedex 1 06001
France
Hopital de la Salpetriere
Paris 75651
France
Bretonneau University Hospital
Tours Cedex 9 37044
France
University of Ulm, Department of Neurology
Ulm, Baden-Wuerttemberg
89081
Germany
Hannover Medical School, Department of Neurology
Hannover, Lower Saxony
30625
Germany
Charite Campus Virchow-Klinikum, Neurology Department
Berlin 13353
Germany
Clinical Research Centre, Beaumont Hospital
Dublin Dublin 9
Ireland
IRCCS Istituto Auxologico Italiano - U.O. Neurologia
Milan 20149
Italy
Centro Clinico NEMO - Fondazione Serena Onlus, ASST Grande Ospedale Metropolitano Niguarda
Milan 20162
Italy
Dipartimento di Neuroscienze "Rita Levi Moltalcini" A.O.U. Citta della Salute e della Scienza di Torino P.O. "Molinette"
Torino 10126
Italy
University Medical Center Utrecht
Utrecht 3584 CX
Netherlands
Hospital Santa Maria-Centro Hospitalar Lisboa Norte
Lisboa 1649-035
Portugal
Hospital San Rafael
Madrid 28016
Spain
Derriford Hospital
Plymouth, Devon
PL6 8DH
United Kingdom
Walton Centre for Neurology and Neurosurgery
Liverpool L9 7LJ
United Kingdom
Clinical Research Centre, Royal London Hospital
London E1 2AT
United Kingdom
Kings College Hospital
London SE59RS
United Kingdom