Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension

NCT ID: NCT03948178

Last Updated: 2023-03-09

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

227 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-26

Study Completion Date

2020-11-18

Brief Summary

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This study provides an opportunity for subjects in the REFALS (3119002; NCT03505021) study to continue treatment with oral levosimendan. The study will also provide more information about long-term safety and effectiveness of oral levosimendan in patients with ALS.

This is an open-label study, so that all eligible subjects that complete the double-blind REFALS study (48-weeks of treatment) will have the opportunity to receive oral levosimendan treatment. The primary objective, in addition to continuing treatment for subjects enrolled in the REFALS study, is to evaluate long-term safety of oral levosimendan in ALS patients. Another important objective is to explore long-term effectiveness of oral levosimendan in the treatment of patients with ALS.

This study is open only to patients taking part in the REFALS study.

Detailed Description

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Conditions

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Amyotrophic Lateral Sclerosis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Levosimendan

Oral Levosimendan; Levosimendan 1mg capsules for oral administration, once to twice a day, continued as long as clinically beneficial. The total study duration is up to 3 years.

Group Type EXPERIMENTAL

Levosimendan

Intervention Type DRUG

Levosimendan 1 mg capsule for oral administration

Interventions

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Levosimendan

Levosimendan 1 mg capsule for oral administration

Intervention Type DRUG

Other Intervention Names

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ODM-109

Eligibility Criteria

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Inclusion Criteria

* Written or verbal informed consent (IC) for participation in the study
* Subjects who completed 48 weeks of treatment according to the REFALS study protocol
* Able to swallow study treatment capsules at the time of completing 48 weeks dosing in the REFALS study

Exclusion Criteria

* Development (or significant worsening from baseline of the REFALS study) of serious cardiovascular disease (e.g.: myocardial infarction, heart failure, arrhythmia, stroke, or second or third degree atrioventricular (AV) block)
* Pulse/heart rate repeatedly \>100 bpm after 5-minute rest at baseline. If the pulse/heart rate is \>100 bpm in the first recording, then a second recording must be done after another 5 min rest to confirm pulse/heart rate \>100 bpm
* Systolic blood pressure (SBP) \<90 mmHg
* Severe renal impairment (creatinine clearance \< 30ml/min or creatine \>170 µmol/l at 48 week visit of the REFALS study, or on dialysis
* Severe hepatic impairment at the discretion of the investigator
* Women of reproductive age without a negative pregnancy test and without a commitment to using a highly effective method of contraception (e.g.: oral hormonal contraceptive associated with inhibition of ovulation, intrauterine devices and long acting progestin agent), 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
* Subject judged to be actively suicidal by the investigator
* Any other clinical 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Geneviève Nadeau, CSD

Role: STUDY_DIRECTOR

Orion Corporation, Orion Pharma

Locations

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Neuromuscular research Centre and Neuromuscular Clinic of Arizona

Phoenix, Arizona, United States

Site Status

University of California San Diego

La Jolla, California, United States

Site Status

University of California Irvine Medical Center

Orange, California, United States

Site Status

Hospital for Special Care

New Britain, Connecticut, United States

Site Status

Georgetown University

Washington D.C., District of Columbia, United States

Site Status

The George Washington Medical Faculty Associates

Washington D.C., District of Columbia, United States

Site Status

Holy Cross Hospital Neuroscience Institute

Fort Lauderdale, Florida, United States

Site Status

University of Florida McKnight Brain Institute

Gainesville, Florida, United States

Site Status

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status

University of South Florida/USF Health

Tampa, Florida, United States

Site Status

Augusta University, Medical Centre

Augusta, Georgia, United States

Site Status

Northwestern University Feinberg School of Medicine

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

University of Michigan, Michigan Medicine University Hospital

Ann Arbor, Michigan, United States

Site Status

Health Partners Speciality Center

Saint Paul, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Neurology Associates

Lincoln, Nebraska, United States

Site Status

Hospital for Special Surgery

New York, New York, United States

Site Status

Columbia Presbyterian Hospital

New York, New York, United States

Site Status

Neurosciences Institute - Neurology Charlotte

Charlotte, North Carolina, United States

Site Status

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

The Ohio State University Wexner Medical center

Columbus, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Providence Brain and Spine Institute

Portland, Oregon, United States

Site Status

Alleghenay General hospital

Pittsburgh, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

Nerve and Muscle Centre of Texas

Houston, Texas, United States

Site Status

University of Utah Health-Imaging & Neurosciences Center in research Park

Salt Lake City, Utah, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Brain and Mind Centre

Camperdown, New South Wales, Australia

Site Status

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

Flinders Medical Centre

Bedford Park, South Australia, Australia

Site Status

Calvary Health Care Bethlehem

Parkdale, Victoria, Australia

Site Status

Perron Institute for Neurological and Translational Science

Nedlands, Western Australia, Australia

Site Status

Medizinische Universitat Innsbruck

Innsbruck, Tyrol, Austria

Site Status

Salzqammergut-klinikum Vocklabruck, Neurologie

Vöcklabruck, Upper Austria, Austria

Site Status

Medizinische Universitat wein Universitatsklinik ffur Neurologie

Wein, , Austria

Site Status

Algemeen Ziekenhuis St Lucas Gent

Ghent, , Belgium

Site Status

Universitair Ziekenhuis Leuven

Leuven, , Belgium

Site Status

Centre Hospitalier Regional de la Vitadelle

Liège, , Belgium

Site Status

Alberta Health Services-Neuromuscular Clinic

Calgary, Alberta, Canada

Site Status

University of Alberta, Division of Neurology

Edmonton, Alberta, Canada

Site Status

Stan Cassidy Centre for Rehabilitation

Fredericton, New Brunswick, Canada

Site Status

McMaster University Medical Centre

Hamilton, Ontario, Canada

Site Status

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Site Status

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

Site Status

Centre Hospitalier Affilie Universitaire de Quebec

Québec, Quebec, Canada

Site Status

Helsinki University Central Hospital, Neurology Outpatients Clinic

Helsinki, , Finland

Site Status

Turku University Hospital

Turku, , Finland

Site Status

Centre Hospitalier Universitaire de Limoges Service de Neurologie

Limoges, , France

Site Status

Hopital Gui de Chauliac Service de Neurologie

Montpellier, , France

Site Status

Hopital Pasteur Centre de reference des Malades Neuromusculaires et SLA

Nice, , France

Site Status

Charite Universitatmedizin Berlin- Campus Virchow-Klinikum

Berlin, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Universitatsklinikum Jena, Klinik fur Neurologie

Jena, , Germany

Site Status

Universitatsklinikum Munster, Institut fur Schalfmedizin und Neuromuskalaire Erkrankungen

Münster, , Germany

Site Status

Universitatsmedizin Rostock, Klinik und Poliklinik fuer Neurologie

Rostock, , Germany

Site Status

Universitatsklinikum Ulm, Poliklinik fur Neurologie

Ulm, , Germany

Site Status

Deutsche Klinik fur Daignostik

Wiesbaden, , Germany

Site Status

Beaumont Hospital, Clinical Research Centre

Dublin, , Ireland

Site Status

Azienda Policlinico San Martino

Genova, , Italy

Site Status

ICS Maugeri Spa S UO Riabilitazione Nurologica

Milan, , Italy

Site Status

Azienda Ospedaliera Universitaria-maggiore della Carita di Novara

Novara, , Italy

Site Status

Azienda Ospedaliero Universitaria Pisana Ospedale Santa Chiara

Pisa, , Italy

Site Status

Policlinico Umberto I di Roma Clinica Neurologica

Rome, , Italy

Site Status

Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino

Torino, , Italy

Site Status

Univeritair Medisch Centrum Utrech

Utrecht, , Netherlands

Site Status

Hospital Universitari de Bellvitge

Barcelona, , Spain

Site Status

Hospital Universitario de Basurto

Bilbao, , Spain

Site Status

Hospital Universitario Reina Sofia Servicio Neurologia

Córdoba, , Spain

Site Status

Hospital San Rafael

Madrid, , Spain

Site Status

Hospital Universitario y Politecnico de La Fe

Valencia, , Spain

Site Status

Karlstad Central Hospital Neurology and Rehabilitation

Karlstad, , Sweden

Site Status

Karolinska University Horpital Huddinge Neurology Clinic

Stockholm, , Sweden

Site Status

Norrlanda University Hospital Neuro-huvud-hals-centrum Vasterbotten

Umeå, , Sweden

Site Status

The Walton Centre NHs Foundation Trust, Neurology and Neurosurgery

Liverpool, , United Kingdom

Site Status

Barts Health NHS Trust Royal London hospital

London, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium Canada Finland France Germany Ireland Italy Netherlands Spain Sweden United Kingdom

References

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Cudkowicz M, Genge A, Maragakis N, Petri S, van den Berg L, Aho VV, Sarapohja T, Kuoppamaki M, Garratt C, Al-Chalabi A; REFALS investigators. Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2021 Oct;20(10):821-831. doi: 10.1016/S1474-4422(21)00242-8.

Reference Type DERIVED
PMID: 34536404 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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3119003

Identifier Type: -

Identifier Source: org_study_id

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