Clinical trial: Effects of ODM-109 on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (NCT02487407)

Eligibility criteria:
Inclusion Criteria:

          -  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).

          -  Age of at least 18 years.

          -  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 compatible with ALS according to an experienced
             neurophysiologist.

          -  Ability to swallow the study treatment capsules.

          -  An upright (sitting position) SVC between 60-90% of the predicted value for age,
             height and sex at screening visit.

          -  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.

          -  Disease duration from symptom onset (defined by first muscle weakness or dysarthria)
             of 12-48 months.

          -  Using riluzole. The dose must have been stable for at least 4 weeks prior to screening
             at a dose of 50 mg b.i.d.

        Exclusion Criteria:

          -  Subject in whom other causes of neuromuscular weakness have not been excluded.

          -  Subject with a diagnosis of another neurodegenerative disease (e.g. Parkinson's or
             Alzheimer's disease).

          -  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.

          -  Recorded diagnosis or evidence of major psychiatric diagnosis, significant cognitive
             impairment or clinically evident dementia.

          -  Any major surgery within 1 month before the screening visit or patients who are
             scheduled for any major surgery during the planned study period.

          -  Potassium < 3.7 mmol/l or > 5.5 mmol/l at screening.

          -  Creatinine > 170 μmol/l at screening or on dialysis.

          -  Blood haemoglobin < 10 g/dl at screening.

          -  Clinically significant hepatic impairment at the discretion of the investigator.

          -  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.

          -  Known hypersensitivity to levosimendan.

          -  Administration of levosimendan within 30 days prior to screening visit.

          -  Patients with history of botulinum toxin treatment for any reason.

          -  Patients with known history of human immunodeficiency virus infection.

          -  History of significant arrhythmias or other cardiac events

          -  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.

          -  Blood donation or loss of significant amount of blood within 60 days prior to
             screening.

          -  Participation in a clinical trial with any experimental treatment within 30 days prior
             to the screening visit or previous participation in the present study.

          -  Any other condition 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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient description (patient's own words): I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Does the patient match the trial criteria? 1