Effects of ODM109 on respiratory function in patients with ALS. A randomised, double blind, placebocontrolled, crossover, 3 period, multicentre study with openlabel followup extension.

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 7

Inclusion Criteria

1. Written informed consent (IC) for participation in the study will be obtained from the subject (or from the subject*s next of kin, caregiver, or other legally acceptable representative in case the study subject him/herself cannot sign the IC due to severe muscle weakness).
2. Age of at least 18 years.
3. Male or female subjects with diagnosis of laboratory supported probable, probable or definite Amyotrophic Lateral Sclerosis (ALS) according to El Escorial revised criteria (Brooks BR et al., 2000). Full electromyogram report available consistent with ALS (but not necessarily fulfilling electrodiagnostic criteria for ALS) according to an experienced neurophysiologist.
4. Ability to swallow the study treatment capsules.
5. An upright (sitting position) Slow Vital Capacity between 60-90% of the predicted value for age, height and sex at screening visit.
6. Normal oxygen saturation during daytime (measure of >= 95% when steady state has been reached with a reliable read) in sitting position measured by pulse oximetry.
7. Disease duration from symptom onset. This is defined by first muscle weakness or difficulty speaking (dysarthria) of 12-48 months at the time of baselin/day 1 of the first treatment period.
8. Patients with or withour riluzole. If using riluzole, the dose must have been stable for at least 4 weeks prior to screening and should not be changed during the cross-over, double blind part of the study.

Exclusion Criteria

1. Subject in whom other causes of neuromuscular weakness have not been excluded.
2. Subject with a diagnosis of another neurodegenerative disease
3. Assisted ventilation or gastrostomy of any type during the preceding 3 months prior to screening or predicted to be required within the randomised, doubleblind crossover
part of the study
4. Recorded diagnosis or evidence of major psychiatric diagnosis, significant cognitive impairment or clinically evident dementia
5. Haemodynamically significant uncorrected valve disease or hypertrophic cardiomyopathy or restrictive cardiomyopathy
6. Acute myocardial infarction or any other acute coronary event within 1 month before the screening visit
7. Any major surgery within 1 month before the screening visit or patients who are scheduled for any major surgery during the planned study period
8. History of Torsades de Pointes, family history of long QTsyndromeor history of lifethreatening
ventricular arrhythmia within 3 months before screening
9. Heart Rate of less than 50 or greater than 100 beats per minute as an average over the 24hour ambulatory HolterECG recording at screening
10. Systolic blood pressure (SBP) less than 100 mmHg or greater than 180 mmHg, or diastolic blood pressure (DBP) greater than 100 mmHg at screening.
11. Ventricular tachycardia (wide complex tachycardia greater than 100/min, greater than 5 consecutive beats) in the 24hour ambulatory HolterECG recording at screening.
12. Episode of atrial fibrillation or atrial flutter lasting greater than 60 seconds in 24hour
ambulatory HolterECG recording at screening.
13. Second or third degree atrioventricular (AV) block in the 12lead ECG or in the 24hour
ambulatory HolterECG recording at screening.
14. Potassium less than 3.7 mmol/l or greater than 5.5 mmol/l at screening
15. Creatinine greater than 170 µmol/l at screening or on dialysis.
16. Blood haemoglobin less than 10 g/dl at screening.
17. Clinically significant hepatic impairment at the discretion of the investigator.
18. 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.
19. Known hypersensitivity to levosimendan.
20. Administration of levosimendan within 30 days prior to screening visit.
21. Any botulinum toxin use within 3 months from screening. Use of botulinum toxin is not allowed during double-blind, cross-over part of the study.
22. Patients with known history of human immunodeficiency virus (HIV) infection.
23. Any other clinically significant cardiovascular, pulmonary, 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.
24. Blood donation or loss of significant amount of blood within 60 days prior to screening.
25. Participation in a clinical trial with any experimen

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Efficacy of levosimendan on respiratory functions.<br /><br>The primary efficacy variable will be the upright slow vital capacity (SVC)<br /><br>measured in sitting position with a spirometer. SVC is the maximum volume of<br /><br>air that can be exhaled slowly after slow maximum inhalation. The best read<br /><br>from 3 assessments will be chosen. The volume is measured in letres and the SVC<br /><br>variable will be % of predicted (normal) value for age, height and sex/ SVC is<br /><br>measured once during screening, three times during each treatment period in the<br /><br>cross-over part of the study and three time during the 6 months open-label part<br /><br>of the study.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Effect oral levosimendan on hand grip strength, hand grip endurance as well as<br /><br>quality of life and daily functions.<br /><br><br /><br>Safety and tolerability of the IMP.<br /><br><br /><br>Effects of the IMP on Riluzole.</p><br>