Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS



Status:Recruiting
Conditions:Neurology, Neurology
Therapuetic Areas:Neurology
Healthy:No
Age Range:18 - 120
Updated:2/8/2019
Start Date:June 21, 2018
End Date:October 30, 2020
Contact:Merit E Cudkowicz, MD
Email:Cudkowicz.Merit@mgh.harvard.edu
Phone:+1 617 726 2383

Use our guide to learn which trials are right for you!

This study will evaluate whether prolonged oral levosimendan can preserve respiratory
function more effectively than placebo, resulting in better patient functionality as measured
by the ALSFRS-R scale. In this randomized, double-blind, placebo-controlled, parallel-group,
multicenter study, subjects are allocated in a 2:1 ratio to receive either levosimendan (1 -2
mg daily) or placebo for 48 weeks. The primary endpoint is slow vital capacity (SVC) at 12
weeks, with the impact on patient function assessed through 48 weeks, adjusted for patient
outcome, using ALSFRS-R (combined assessment of function and survival, CAFS). Other important
efficacy measures include time to respiratory events, clinical global impression (CGI),
assessment of dyspnea using the Borg scale and sleep scales (Pittsburgh sleep quality index
and Epworth sleepiness scale). Patient safety is monitored using conventional methods
including adverse events, safety laboratory tests, vital signs and 12-lead EKG. Following
screening and baseline visits, patients attend the clinic at 2, 4, 8, 12, 24, 36 and 48
weeks, with telephone assessments conducted at weeks 18, 30 and 42. An end of study visit is
performed 14-25 days after the last study treatment administration. The study will be
monitored by an independent data and safety monitoring board. A long-term extension study
will be available for patients completing the study.


Inclusion Criteria:

- Written or verbal informed consent (IC) for participation in the study

- Male or female subjects with diagnosis of laboratory supported probable, probable or
definite ALS according to El Escorial revised criteria. Full electromyogram (EMG)
report available consistent with ALS (but not necessarily fulfilling the
electrodiagnostic criteria for ALS) from an experienced neurophysiologist

- Able to swallow study treatment capsules, and in the opinion of the investigator, is
expected to continue to do so during the study

- Sitting SVC between 60-90% of the predicted value for age, height and sex at screening
visit

- Disease duration from symptom onset (defined by first muscle weakness or dysarthria)
12-48 months at the time of visit 1 (baseline)

- Able to perform supine SVC in an adequate and reliable way at screening and baseline
visits as judged by the investigator

- Subjects with or without riluzole and/or edaravone. If using riluzole (any daily dose
up to 100 mg), the dose must have been stable for at least 4 weeks before the
screening visit and should not be changed during the study. If using edaravone, the
treatment should have been started at least 4 weeks before the screening visit (at
least one 28-day treatment cycle as indicated) and should not be changed during the
study. If not on riluzole and/or edaravone, the respective treatments should not be
started during the study

Exclusion Criteria:

- Subject in whom other causes of neuromuscular weakness have not been excluded

- Subject with a diagnosis of another neurodegenerative disease (e.g. Parkinson's or
Alzheimer's disease)

- Assisted ventilation of any type within 3 months before the screening visit or at
screening

- Any use of a diaphragm pacing system (DPS) within 3 months before the screening visit

- Any form of stem cell or gene therapy for the treatment of ALS

- Known hypersensitivity to levosimendan

- Administration of levosimendan within 3 months before the screening visit or previous
participation in the present phase III study or earlier study with oral levosimendan
in ALS patients (LEVALS)

- Any use of tirasemtiv or reldesemtiv within 1 month before the screening visit.

- Participation in a clinical trial with any experimental treatment within 30 days or
within 5 half-lives of that treatment (whichever is longer) before the screening visit

- Any botulinum toxin use within 3 months before the screening visit

- Recorded diagnosis or evidence of major psychiatric diagnosis, significant cognitive
impairment or clinically evident dementia that may interfere with the patient's
ability to comply with study procedures

- Pulmonary illness (e.g. asthma or COPD) requiring regular treatment

- Haemodynamically significant uncorrected valve disease or hypertrophic cardiomyopathy
or restrictive cardiomyopathy

- Any cardiovascular event (e.g. myocardial infarction, HF, arrhythmia or stroke)
requiring hospitalisation within 3 months before the screening visit

- History of Torsades de Pointes (TdP) or diagnosed long QT-syndrome

- History of life-threatening ventricular arrhythmia, unless treated with reliable
measures to prevent recurrence (e.g. with placement of implantable cardioverter
defibrillator [ICD] or catheter ablation)

- History of second or third degree atrioventricular (AV) block or sinus node disease at
screening, if not treated with pacemaker

- HR repeatedly > 100 bpm in the 12-lead ECG after a 5-minute rest at screening. If the
HR is > 100 bpm in the first recording, then the second recording must be done after
another 5 min rest to confirm HR > 100 bpm

- Systolic blood pressure (SBP) < 90 mmHg at screening

- Potassium < 3.7 mmol/l or > 5.5 mmol/l at screening

- Severe renal impairment (creatinine clearance < 30 ml/min at screening), creatinine >
170 μmol/l at screening or on dialysis

- Blood haemoglobin < 10 g/dl at screening or blood donation or loss of significant
amount of blood within 60 days before the screening visit

- Clinically significant hepatic impairment at the discretion of the investigator

- Body mass index (BMI) ≤ 18.5kg/m2 (BMI = weight/height2)

- Women who are lactating or of reproductive age without a negative pregnancy test and
without a commitment to using a highly effective method of contraception (e.g. oral
hormonal contraceptives associated with inhibition of ovulation, intrauterine devices
and long acting progestin agents), if sexually active during the study, and for 1
month after the last dose of the study treatment. Women who are postmenopausal (1 year
since last menstrual cycle), surgically sterilised or who have undergone a
hysterectomy are considered not to be reproductive and can be included

- Patient judged to be actively suicidal by the investigator during 3 months before the
screening visit

- Patients with known history of human immunodeficiency virus (HIV) infection

- Any other clinically significant cardiovascular, gastrointestinal, hepatic, renal,
neurological or psychiatric disorder or any other major concurrent illness that in the
opinion of the investigator could interfere with the interpretation of the study
results or constitute a health risk for the subject if he/she took part in the study
We found this trial at
48
sites
Orange, California 92868
Phone: 714-546-8323
?
mi
from
Orange, CA
Click here to add this to my saved trials
1648 Pierce Dr NE
Atlanta, Georgia 30322
(404) 727-5640
Emory University School of Medicine Emory University School of Medicine has 2,359 full- and part-time...
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
Phone: 617-643-2522
?
mi
from
Boston, MA
Click here to add this to my saved trials
Gainesville, Florida 32610
(352) 392-3261
University of Florida The University of Florida (UF) is a major, public, comprehensive, land-grant, research...
?
mi
from
Gainesville, FL
Click here to add this to my saved trials
8700 Beverly Blvd # 8211
Los Angeles, California 90048
(1-800-233-2771)
Phone: 310-423-8497
Cedars Sinai Med Ctr Cedars-Sinai is known for providing the highest quality patient care. Our...
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
2150 Corbin Avenue
New Britain, Connecticut 06053
Phone: 860-612-6356
?
mi
from
New Britain, CT
Click here to add this to my saved trials
3400 Spruce St
Philadelphia, Pennsylvania 19104
 (215) 662-4000
Phone: 215-829-5041
Hospital of the University of Pennsylvania The Hospital of the University of Pennsylvania (HUP) is...
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
5090 N 40th St # 250
Phoenix, Arizona 85018
?
mi
from
Phoenix, AZ
Click here to add this to my saved trials
3181 Southwest Sam Jackson Park Road
Portland, Oregon 97239
503 494-8311
Phone: 503-494-7394
Oregon Health and Science University In 1887, the inaugural class of the University of Oregon...
?
mi
from
Portland, OR
Click here to add this to my saved trials
4202 E Fowler Ave
Tampa, Florida 33620
(813) 974-2011
Phone: 813-974-9413
University of South Florida The University of South Florida is a high-impact, global research university...
?
mi
from
Tampa, FL
Click here to add this to my saved trials
500 S State St
Ann Arbor, Michigan 48109
(734) 764-1817
Phone: 734-936-8776
University of Michigan The University of Michigan was founded in 1817 as one of the...
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
Augusta, Georgia 30912
?
mi
from
Augusta, GA
Click here to add this to my saved trials
1800 Orleans St.
Baltimore, Maryland 21287
410-955-5000
Johns Hopkins Hospital Patients are the focus of everything we do at The Johns Hopkins...
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Burlington, Vermont 05405
Phone: 802-656-4582
?
mi
from
Burlington, VT
Click here to add this to my saved trials
Camperdown, New South Wales
Phone: 02 9351 0976 or 029114 4250
?
mi
from
Camperdown,
Click here to add this to my saved trials
Charlotte, North Carolina 28207
?
mi
from
Charlotte, NC
Click here to add this to my saved trials
303 E Chicago Ave
Chicago, Illinois 60611
(312) 503-8194
Northwestern University Feinberg School of Medicine Northwestern University Feinberg School of Medicine, founded in 1859,...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Colorado Springs, Colorado 80907
Phone: 719-389-1129
?
mi
from
Colorado Springs, CO
Click here to add this to my saved trials
281 W. Lane Ave
Columbus, Ohio 43210
(614) 292-6446
Ohio State University The Ohio State University’s main Columbus campus is one of America’s largest...
?
mi
from
Columbus, OH
Click here to add this to my saved trials
Dallas, Texas 75214
Phone: 214-827-3610
?
mi
from
Dallas, TX
Click here to add this to my saved trials
2301 Erwin Rd
Durham, North Carolina 27710
919-684-8111
Phone: 919-668-2844
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
?
mi
from
Durham, NC
Click here to add this to my saved trials
Fort Lauderdale, Florida 33308
Phone: 954-489-4314
?
mi
from
Fort Lauderdale, FL
Click here to add this to my saved trials
Houston, Texas 77030
Phone: 713-795-0033
?
mi
from
Houston, TX
Click here to add this to my saved trials
Jacksonville, Florida 32209
?
mi
from
Jacksonville, FL
Click here to add this to my saved trials
Jacksonville, Florida 32216
?
mi
from
Jacksonville, FL
Click here to add this to my saved trials
9500 Gilman Dr
La Jolla, California 92093
(858) 534-2230
The University of California, San Diego UC San Diego is an academic powerhouse and economic...
?
mi
from
La Jolla, CA
Click here to add this to my saved trials
Lexington, Kentucky 40536
Phone: 859-218-5046
?
mi
from
Lexington, KY
Click here to add this to my saved trials
Lincoln, Nebraska 68506
Phone: 402-770-7403
?
mi
from
Lincoln, NE
Click here to add this to my saved trials
Louisville, Kentucky 40202
Phone: 502-540-3585
?
mi
from
Louisville, KY
Click here to add this to my saved trials
Milwaukee, Wisconsin 53226
Phone: 414-805-9307
?
mi
from
Milwaukee, WI
Click here to add this to my saved trials
New York, New York 10003
Phone: 212-844-8490
?
mi
from
New York, NY
Click here to add this to my saved trials
535 E 70th St
New York, New York 10021
(212) 606-1000
Phone: 646-797-8592
Hospital for Special Surgery Founded in 1863, Hospital for Special Surgery is the nation
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10021
?
mi
from
New York, NY
Click here to add this to my saved trials
Philadelphia, Pennsylvania 19140
Phone: 215-707-4171
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Phoenix, Arizona 85028
Phone: 480-314-1007
?
mi
from
Phoenix, AZ
Click here to add this to my saved trials
200 Lothrop St
Pittsburgh, Pennsylvania 15213
Phone: 412-864-2873
University of Pittsburgh Medical Center UPMC is one of the leading nonprofit health systems in...
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
320 E North Ave
Pittsburgh, Pennsylvania 15212
(412) 359-3131
Allegheny General Hospital At Allegheny General Hospital, our physicians and healthcare staff have earned an...
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
Portland, Oregon 97225
Phone: 503-962-1171
?
mi
from
Portland, OR
Click here to add this to my saved trials
200 First Street SW
Rochester, Minnesota 55905
507-284-2511
Mayo Clinic Rochester Mayo Clinic is a nonprofit worldwide leader in medical care, research and...
?
mi
from
Rochester, MN
Click here to add this to my saved trials
660 S Euclid Ave
Saint Louis, Missouri 63110
(314) 362-5000
Washington University School of Medicine Washington University Physicians is the clinical practice of the School...
?
mi
from
Saint Louis, MO
Click here to add this to my saved trials
Saint Paul, Minnesota 55130
Phone: 651-495-6363
?
mi
from
Saint Paul, MN
Click here to add this to my saved trials
Salt Lake City, Utah 84108
Phone: 801-585-7575
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials
45 Castro Street
San Francisco, California 94114
(415) 600-6000
California Pacific Medical Center California Pacific Medical Center is one of the largest private, not-for-profit,...
?
mi
from
San Francisco, CA
Click here to add this to my saved trials
Seattle, Washington 98122
Phone: 206-320-2334
?
mi
from
Seattle, WA
Click here to add this to my saved trials
1959 NE Pacific St
Seattle, Washington 98195
(206) 598-3300
Phone: 206-543-0081
University of Washington Medical Center University of Washington Medical Center is one of the nation's...
?
mi
from
Seattle, WA
Click here to add this to my saved trials
Washington, District of Columbia 20037
Phone: 202-741-2745
?
mi
from
Washington,
Click here to add this to my saved trials
3700 O St NW
Washington, District of Columbia 20057
(202) 687-0100
Phone: 202-444-6941
Georgetown University Georgetown University is one of the world's leading academic and research institutions, offering...
?
mi
from
Washington,
Click here to add this to my saved trials
1 Medical Center Blvd
Winston-Salem, North Carolina 27103
(336) 716-2011
Phone: 336-713-8577
Wake Forest University Baptist Medical Center Welcome to Wake Forest Baptist Medical Center, a fully...
?
mi
from
Winston-Salem, NC
Click here to add this to my saved trials