Effects of oral Levosimendan on breathing function in patients with the disease Amyotrophic Lateral Sclerosis (ALS)

Phase 1

• Conditions: Amyotrophic lateral sclerosis (ALS); MedDRA version: 20.0Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2017-002754-36-ES
• Lead Sponsor: Orion Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-03-14
• Study Completion: 2020-06-26
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 496

Inclusion Criteria

1. Written or verbal informed consent (IC) for participation in the study will be obtained from the subject. In case that the study subject him/herself cannot sign the IC due to severe muscle weakness, a witness may sign the consent form to indicate that the subject has given verbal consent.
2. Age at least 18 years.
3. Male or female subjects with diagnosis of laboratory supported probable, probable or definite ALS according to El Escorial revised criteria (Brooks BR et al., 2000). Full electromyogram (EMG) report available consistent with ALS (but not necessarily fulfilling the electrodiagnostic criteria for ALS) from an experienced neurophysiologist.
4. Able to swallow study treatment capsules, and in the opinion of the investigator, is expected to continue to do so during the study.
5. Sitting SVC between 60-90% of the predicted value for age, height and sex at screening visit.
6. Disease duration from symptom onset (defined by first muscle weakness or dysarthria) 12- 48 months at the time of visit 1 (baseline).
7. Able to perform supine SVC in an adequate and reliable way at screening and baseline visits as judged by the investigator.
8. Subjects with or without riluzole. 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 not on riluzole, the subjects should not start riluzole during the study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 440
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. Subject in whom other causes of neuromuscular weakness have not been excluded.
2. Subject with a diagnosis of another neurodegenerative disease (e.g. Parkinson’s or Alzheimer’s disease).
3. Assisted ventilation of any type within 3 months before the screening visit or at screening.
4. Any use of a diaphragm pacing system (DPS) within 3 months before the screening visit.
5. Any form of stem cell or gene therapy for the treatment of ALS.
6. Known hypersensitivity to levosimendan.
7. 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).
8. Any use of edaravone, tirasemtiv or CK-2127107 within 1 month before the screening visit.
9. 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.
10. Any botulinum toxin use within 3 months before the screening visit.
11. 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.
12. Pulmonary illness (e.g. asthma or COPD) requiring regular treatment.
13. Haemodynamically significant uncorrected valve disease or hypertrophic cardiomyopathy or restrictive cardiomyopathy.
14. Any cardiovascular event (e.g. myocardial infarction, HF, arrhythmia or stroke) requiring hospitalisation within 3 months before the screening visit.
15. History of Torsades de Pointes (TdP) or diagnosed long QT-syndrome.
16. 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).
17. History of second or third degree atrioventricular (AV) block or sinus node disease at screening, if not treated with pacemaker.
18. 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.
19. Systolic blood pressure (SBP) < 90 mmHg at screening.
20. Potassium < 3.7 mmol/l or > 5.5 mmol/l at screening.
21. Creatinine > 170 µmol/l at screening or on dialysis.
22. Blood haemoglobin < 10 g/dl at screening or blood donation or loss of significant amount of blood within 60 days before the screening visit.
23. Clinically significant hepatic impairment at the discretion of the investigator.
24. Body mass index (BMI) = 18.5kg/m2 (BMI = weight/height2).
25. Women of reproductive age without a negative pregnancy test and without a commitment to using an acceptable method of barrier or hormonal contraception (e.g. condoms, diaphragms, oral contraceptives 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.
26. Patient judged to be actively suicidal by the investigator during 3 months before the screening visit.
27. Patients with known history of human immunodeficiency virus (HIV) infection.
28. Any other clinically significant cardiovascular, gastrointestinal, hepatic, renal, neurological or psychiatr

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified