Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
- Registration Number
- NCT03948178
- Lead Sponsor
- Orion Corporation, Orion Pharma
- Brief Summary
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
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 227
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Levosimendan 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.
- Primary Outcome Measures
Name Time Method Adverse Events Recording From signing informed consent until 14-25 days after the last study treatment for all patients, an average of 23.5 weeks. Adverse Events as subject counts and proportions (%) of subject per Adverse Event
12-lead Electrocardiogram Assessments Baseline, week 2, week 4, month 3, month 6, end-of-study(subject's last visit, 2-48 weeks after study entry) Summarisation of any abnormal 12-lead ECG findings using descriptive statistics.
Pulse/Heart Rate Assessment Change in pulse and heart rate(from ECG recording) from Baseline, week 2, week 4, week 6 (pulse rate only), Month 3, Month 6, end of study (subject's last visit, 2-48 weeks after study entry) Actual values and changes from baseline in supine pre-dose pulse/heart rate were summarised using descriptive statistics .
- Secondary Outcome Measures
Name Time Method Need for Respiratory Support Device Time to event at study completion (subject's last visit, 2-48 weeks after study entry) Time to respiratory device support (non invasive) or death
Subject's Status for Tracheostomy and Survival Baseline to end of study (average 2-48 weeks after study entry Number of patients with the need for tracheostomy or who died whilst on treatment from baseline to the end of the study was summarised using descriptive statistics.
Health Care Service Use During the Study(Visits to the Emergency Room) From baseline to the end of the study(2-48 weeks after study entry) The number of visits to the emergency room were recorded throughout the study using a diary given to the study subjects
Supine Slow Vital Capacity (SVC) The change from Baseline, week 2, week 4, month 3, month 6, end-of-study (subject's last visit, 2-48 weeks after study entry) Change from baseline in supine and sitting SVC (all devices) through to the end of the study, expressed as a % of predicted normal
Borg Category Ratio 10 Scale (CR 10) Baseline through study completion (week 2, week 4, month 3, month 6, end of study (subject's last visit, 2-48 weeks after study entry) Patients rated their perception of the severity of their dyspnea using the Borg Category Ration 10 scale (CR 10). The scale ranges from 0(no dysponea) to 10 (maximal dyspnea). each category is numbered and most but not all have verbal cues. At each assessment the patient scored the category they felt best described their symptoms. The analysis measured change from baseline to the end of the study in both a supine and sitting position where a negative score indicates improvement and a positive score reflects worsening.
Number of Subjects Requiring Health and Home Care Resource Use Baseline through study completion (2- 48 weeks after study entry) The number of study subjects requiring Health and home care resource use was aggregated over the course of the study for each subject and summarised using descriptive statistics.
Health Care Service Use During the Study(Stays in Hospital) From baseline to the end of the study(2-48 weeks after study entry) The number of night stays in hospital were recorded throughout the study using a diary given to the study subjects
Health Care Service Use During the Study (Days Spent in an Institutional Facility) From baseline to the end of the study(2-48 weeks after study entry) The number of days spent in an institutional facility were recorded throughout the study using a diary given to the study subjects
Disease Progression From Baseline through study completion(subject's last visit, 2-48 weeks after study entry) Count of study withdrawals due to disease progression
Revised ALS Functional Rating Scale (ALSFRS-R) Change from Baseline in respiratory function of ALSFRS-R at study completion (subject's last visit, 2-48 weeks after study entry) ALSFRS-R scale contains 3 parameters related to respiratory function: Severity of dyspnea, occurrence of orthopnea (shortness of breath when in supine position i.e. lying flat), and the use of mechanical ventilation for respiratory in sufficiency. These 3 parameters are combined to create the respiratory domain with a score of 0-12(where 12 is normal function). Although individual items and patients vary, ALSFRS-R typically declines at a relatively constant rate over time. Plotted over time the slope of the line obtained indicates the speed of progression and thus an effective treatment might be expected ro reduce the slope of decline.
Trial Locations
- Locations (79)
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Augusta University, Medical Centre
🇺🇸Augusta, Georgia, United States
Neurology Associates
🇺🇸Lincoln, Nebraska, United States
The Ohio State University Wexner Medical center
🇺🇸Columbus, Ohio, United States
Alleghenay General hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Nerve and Muscle Centre of Texas
🇺🇸Houston, Texas, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Perron Institute for Neurological and Translational Science
🇦🇺Nedlands, Western Australia, Australia
Centre Hospitalier Regional de la Vitadelle
🇧🇪Liège, Belgium
Medizinische Universitat Innsbruck
🇦🇹Innsbruck, Tyrol, Austria
Hospital for Special Care
🇺🇸New Britain, Connecticut, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Algemeen Ziekenhuis St Lucas Gent
🇧🇪Gent, Belgium
Calvary Health Care Bethlehem
🇦🇺Parkdale, Victoria, Australia
Universitair Ziekenhuis Leuven
🇧🇪Leuven, Belgium
Univeritair Medisch Centrum Utrech
🇳🇱Utrecht, Netherlands
Georgetown University
🇺🇸Washington, District of Columbia, United States
The George Washington Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
University of Alberta, Division of Neurology
🇨🇦Edmonton, Alberta, Canada
Alberta Health Services-Neuromuscular Clinic
🇨🇦Calgary, Alberta, Canada
Norrlanda University Hospital Neuro-huvud-hals-centrum Vasterbotten
🇸🇪Umeå, Sweden
The Walton Centre NHs Foundation Trust, Neurology and Neurosurgery
🇬🇧Liverpool, United Kingdom
Barts Health NHS Trust Royal London hospital
🇬🇧London, United Kingdom
Medizinische Universitat wein Universitatsklinik ffur Neurologie
🇦🇹Wein, Austria
Charite Universitatmedizin Berlin- Campus Virchow-Klinikum
🇩🇪Berlin, Germany
Montreal Neurological Institute and Hospital
🇨🇦Montréal, Quebec, Canada
Centre Hospitalier Affilie Universitaire de Quebec
🇨🇦Québec, Quebec, Canada
Turku University Hospital
🇫🇮Turku, Finland
Beaumont Hospital, Clinical Research Centre
🇮🇪Dublin, Ireland
Azienda Ospedaliera Universitaria-maggiore della Carita di Novara
🇮🇹Novara, Italy
Hospital Universitario Reina Sofia Servicio Neurologia
🇪🇸Córdoba, Spain
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Ontario, Canada
Karlstad Central Hospital Neurology and Rehabilitation
🇸🇪Karlstad, Sweden
Hospital Universitario y Politecnico de La Fe
🇪🇸Valencia, Spain
Stan Cassidy Centre for Rehabilitation
🇨🇦Fredericton, New Brunswick, Canada
Universitatsklinikum Jena, Klinik fur Neurologie
🇩🇪Jena, Germany
Helsinki University Central Hospital, Neurology Outpatients Clinic
🇫🇮Helsinki, Finland
Azienda Policlinico San Martino
🇮🇹Genova, Italy
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Hospital San Rafael
🇪🇸Madrid, Spain
Hopital Gui de Chauliac Service de Neurologie
🇫🇷Montpellier, France
Hopital Pasteur Centre de reference des Malades Neuromusculaires et SLA
🇫🇷Nice, France
ICS Maugeri Spa S UO Riabilitazione Nurologica
🇮🇹Milan, Italy
Azienda Ospedaliero Universitaria Pisana Ospedale Santa Chiara
🇮🇹Pisa, Italy
Policlinico Umberto I di Roma Clinica Neurologica
🇮🇹Rome, Italy
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
🇮🇹Torino, Italy
Karolinska University Horpital Huddinge Neurology Clinic
🇸🇪Stockholm, Sweden
Centre Hospitalier Universitaire de Limoges Service de Neurologie
🇫🇷Limoges, France
Universitatsklinikum Munster, Institut fur Schalfmedizin und Neuromuskalaire Erkrankungen
🇩🇪Münster, Germany
Universitatsmedizin Rostock, Klinik und Poliklinik fuer Neurologie
🇩🇪Rostock, Germany
Universitatsklinikum Ulm, Poliklinik fur Neurologie
🇩🇪Ulm, Germany
Deutsche Klinik fur Daignostik
🇩🇪Wiesbaden, Germany
Neuromuscular research Centre and Neuromuscular Clinic of Arizona
🇺🇸Phoenix, Arizona, United States
University of South Florida/USF Health
🇺🇸Tampa, Florida, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Providence Brain and Spine Institute
🇺🇸Portland, Oregon, United States
University of Utah Health-Imaging & Neurosciences Center in research Park
🇺🇸Salt Lake City, Utah, United States
University of California Irvine Medical Center
🇺🇸Orange, California, United States
Holy Cross Hospital Neuroscience Institute
🇺🇸Fort Lauderdale, Florida, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Health Partners Speciality Center
🇺🇸Saint Paul, Minnesota, United States
Neurosciences Institute - Neurology Charlotte
🇺🇸Charlotte, North Carolina, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Columbia Presbyterian Hospital
🇺🇸New York, New York, United States
Hospital for Special Surgery
🇺🇸New York, New York, United States
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Brain and Mind Centre
🇦🇺Camperdown, New South Wales, Australia
Flinders Medical Centre
🇦🇺Bedford Park, South Australia, Australia
Salzqammergut-klinikum Vocklabruck, Neurologie
🇦🇹Vocklabruck, Upper Austria, Austria
Hospital Universitario de Basurto
🇪🇸Bilbao, Spain
University of Michigan, Michigan Medicine University Hospital
🇺🇸Ann Arbor, Michigan, United States
University of Florida McKnight Brain Institute
🇺🇸Gainesville, Florida, United States
Wake Forest University Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
McMaster University Medical Centre
🇨🇦Hamilton, Ontario, Canada