Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Levosimendan
Intervention description: Levosimendan 1 mg capsule for oral administration
Intervention MeSH terms: Simendan
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 227.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No

Summary:

      This study provides an opportunity for subjects in the REFALS (3119002; NCT03505021) study to
      continue treatment with oral levosimendan. The study will also provide more information about
      long-term safety and effectiveness of oral levosimendan in patients with ALS.

      This is an open-label study, so that all eligible subjects that complete the double-blind
      REFALS study (48-weeks of treatment) will have the opportunity to receive oral levosimendan
      treatment. The primary objective, in addition to continuing treatment for subjects enrolled
      in the REFALS study, is to evaluate long-term safety of oral levosimendan in ALS patients.
      Another important objective is to explore long-term effectiveness of oral levosimendan in the
      treatment of patients with ALS.

      This study is open only to patients taking part in the REFALS study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written or verbal informed consent (IC) for participation in the study

          -  Subjects who completed 48 weeks of treatment according to the REFALS study protocol

          -  Able to swallow study treatment capsules at the time of completing 48 weeks dosing in
             the REFALS study

        Exclusion Criteria:

          -  Development (or significant worsening from baseline of the REFALS study) of serious
             cardiovascular disease (e.g.: myocardial infarction, heart failure, arrhythmia,
             stroke, or second or third degree atrioventricular (AV) block)

          -  Pulse/heart rate repeatedly >100 bpm after 5-minute rest at baseline. If the
             pulse/heart rate is >100 bpm in the first recording, then a second recording must be
             done after another 5 min rest to confirm pulse/heart rate >100 bpm

          -  Systolic blood pressure (SBP) <90 mmHg

          -  Severe renal impairment (creatinine clearance < 30ml/min or creatine >170 µmol/l at 48
             week visit of the REFALS study, or on dialysis

          -  Severe hepatic impairment at the discretion of the investigator

          -  Women of reproductive age without a negative pregnancy test and without a commitment
             to using a highly effective method of contraception (e.g.: oral hormonal contraceptive
             associated with inhibition of ovulation, intrauterine devices and long acting
             progestin agent), 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

          -  Subject judged to be actively suicidal by the investigator

          -  Any other clinical significant cardiovascular, 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