Effects of ODM-109 on respiratory function in patients with ALS.

Phase 1

• Conditions: Amyotrophic lateral sclerosis (ALS). A rapidly progressive neurological disease characterized by degeneration of upper and lower motor neurons with subsequent muscle atrophy and weakness and loss of respiratory function. The latter is due to the weakness and loss of the diaphragm muscle strength.; MedDRA version: 17.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2014-004567-21-GB
• Lead Sponsor: Orion Corporation Orion Pharma

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-03-10
• Study Completion: 2017-05-11
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 66

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 compatible with 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.

8. Using riluzole. The dose must have been stable for at least 4 weeks prior to screening at a dose of 50 mg twice a day (B.I.D.).
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 35

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, double-blind cross-over 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 QT-syndrome or history of life-threatening ventricular arrhythmia within 3 months before screening

9. Heart Rate of less that 50 or greater than 100 beats per minute as an average over the 24-hour ambulatory Holter-ECG 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 24-hour ambulatory Holter-ECG recording at screening.

12. Episode of atrial fibrillation or atrial flutter lasting greater than 60 seconds in 24-hour ambulatory Holter-ECG recording at screening.

13. Second or third degree atrioventricular (AV) block in the 12-lead ECG or in the 24-hour ambulatory Holter-ECG 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. Patients with history of botulinum toxin treatment for any reason.

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 resu

Study & Design

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