Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS: Open-Label Extension for Patients Completing Study 3119002
Trial Snapshot
- Phase
- Phase 3
- Status
- Terminated
- Enrollment
- 227
- Locations
- 79
- Primary Endpoint
- Adverse Events Recording
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 120 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Levosimendan
Oral Levosimendan; Levosimendan 1mg capsules for oral administration, once to twice a day, continued as long as clinically beneficial. The total study duration is up to 3 years.
Intervention: Levosimendan (Drug)
Outcomes
Primary Outcomes
Adverse Events Recording
Time Frame: From signing informed consent until 14-25 days after the last study treatment for all patients, an average of 23.5 weeks.
Adverse Events as subject counts and proportions (%) of subject per Adverse Event
12-lead Electrocardiogram Assessments
Time Frame: Baseline, week 2, week 4, month 3, month 6, end-of-study(subject's last visit, 2-48 weeks after study entry)
Summarisation of any abnormal 12-lead ECG findings using descriptive statistics.
Pulse/Heart Rate Assessment
Time Frame: Change in pulse and heart rate(from ECG recording) from Baseline, week 2, week 4, week 6 (pulse rate only), Month 3, Month 6, end of study (subject's last visit, 2-48 weeks after study entry)
Actual values and changes from baseline in supine pre-dose pulse/heart rate were summarised using descriptive statistics .
Secondary Outcomes
- Need for Respiratory Support Device(Time to event at study completion (subject's last visit, 2-48 weeks after study entry))
- Subject's Status for Tracheostomy and Survival(Baseline to end of study (average 2-48 weeks after study entry)
- Health Care Service Use During the Study(Visits to the Emergency Room)(From baseline to the end of the study(2-48 weeks after study entry))
- Supine Slow Vital Capacity (SVC)(The change from Baseline, week 2, week 4, month 3, month 6, end-of-study (subject's last visit, 2-48 weeks after study entry))
- Borg Category Ratio 10 Scale (CR 10)(Baseline through study completion (week 2, week 4, month 3, month 6, end of study (subject's last visit, 2-48 weeks after study entry))
- Number of Subjects Requiring Health and Home Care Resource Use(Baseline through study completion (2- 48 weeks after study entry))
- Health Care Service Use During the Study(Stays in Hospital)(From baseline to the end of the study(2-48 weeks after study entry))
- Health Care Service Use During the Study (Days Spent in an Institutional Facility)(From baseline to the end of the study(2-48 weeks after study entry))
- Disease Progression(From Baseline through study completion(subject's last visit, 2-48 weeks after study entry))
- Revised ALS Functional Rating Scale (ALSFRS-R)(Change from Baseline in respiratory function of ALSFRS-R at study completion (subject's last visit, 2-48 weeks after study entry))