Effects of oral Levosimendan on breathing function in patients with the disease Amyotrophic Lateral Sclerosis (ALS)
- Conditions
- Amyotrophic lateral sclerosis (ALS)MedDRA version: 21.1Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- EUCTR2017-002754-36-IT
- Lead Sponsor
- ORION CORPORATION ORION PHARMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 496
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 and/or edavarone. 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 edavarone, 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 edavarone, the respective tretments should not be started 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
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 tirasemtiv or reldesemtiv 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 QTsyndrome.
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 pbm.
19. Systolic blood pressure (SBP) < 90 mmHg at screening.
20. Potassium < 3.7 mmol/l or > 5.5 mmol/l at screening.
21. Severe renal impairment (cretinine clearance <30 ml/min at screening), 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 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 associates with inhibition of ovulation, intrauterine devices and long acting progestin agents), if sexually active during the study, and for 1 month after 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method