Amyotrophic Lateral Sclerosis
Conditions
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.
Interventions
DRUGLevosimendan
Levosimendan 1 mg capsule for oral administration
Sponsors
Orion Corporation, Orion Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events Recording | 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 |
| Pulse/Heart Rate Assessment | 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 . |
| 12-lead Electrocardiogram Assessments | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Need for Respiratory Support Device | Time to event at study completion (subject's last visit, 2-48 weeks after study entry) | Time to respiratory device support (non invasive) or death |
| 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) | Patients rated their perception of the severity of their dyspnea using the Borg Category Ration 10 scale (CR 10). The scale ranges from 0(no dysponea) to 10 (maximal dyspnea). each category is numbered and most but not all have verbal cues. At each assessment the patient scored the category they felt best described their symptoms. The analysis measured change from baseline to the end of the study in both a supine and sitting position where a negative score indicates improvement and a positive score reflects worsening. |
| Number of Subjects Requiring Health and Home Care Resource Use | Baseline through study completion (2- 48 weeks after study entry) | The number of study subjects requiring Health and home care resource use was aggregated over the course of the study for each subject and summarised using descriptive statistics. |
| Disease Progression | From Baseline through study completion(subject's last visit, 2-48 weeks after study entry) | Count of study withdrawals due to disease progression |
| Health Care Service Use During the Study(Stays in Hospital) | From baseline to the end of the study(2-48 weeks after study entry) | The number of night stays in hospital were recorded throughout the study using a diary given to the study subjects |
| 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) | The number of visits to the emergency room were recorded throughout the study using a diary given to the study subjects |
| 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) | The number of days spent in an institutional facility were recorded throughout the study using a diary given to the study subjects |
| Subject's Status for Tracheostomy and Survival | Baseline to end of study (average 2-48 weeks after study entry | Number of patients with the need for tracheostomy or who died whilst on treatment from baseline to the end of the study was summarised using descriptive statistics. |
| 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) | Change from baseline in supine and sitting SVC (all devices) through to the end of the study, expressed as a % of predicted normal |
| 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) | ALSFRS-R scale contains 3 parameters related to respiratory function: Severity of dyspnea, occurrence of orthopnea (shortness of breath when in supine position i.e. lying flat), and the use of mechanical ventilation for respiratory in sufficiency. These 3 parameters are combined to create the respiratory domain with a score of 0-12(where 12 is normal function). Although individual items and patients vary, ALSFRS-R typically declines at a relatively constant rate over time. Plotted over time the slope of the line obtained indicates the speed of progression and thus an effective treatment might be expected ro reduce the slope of decline. |
Countries
Australia, Austria, Belgium, Canada, Finland, France, Germany, Ireland, Italy, Netherlands, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
Patients with amyotrophic lateral sclerosis (ALS) who completed 48 weeks of treatment in the REFALS study (NCT03505021) were recruited
Pre-assignment details
Male or female subjects with a diagnosis of probable or definite ALS having completed 48 weeks of treatment in the REFALS Study (NCT03505021) and able to swallow study treatment capsules at the time of completing 48 weeks of dosing in the REFALS study. Written or verbal informed consent obtained.
Participants by arm
| Arm | Count |
|---|---|
| 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.
Levosimendan: Levosimendan 1 mg capsule for oral administration | 227 |
| Total | 227 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Disease progression | 30 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Personal reason | 14 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Reason not known | 2 |
| Overall Study | Sponsor terminated study | 164 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Levosimendan |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 67 Participants |
| Age, Categorical Between 18 and 65 years | 160 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 224 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) White | 218 Participants |
| Sex: Female, Male Female | 85 Participants |
| Sex: Female, Male Male | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 227 |
| other Total, other adverse events | 215 / 227 |
| serious Total, serious adverse events | 44 / 227 |
Outcome results
Primary
12-lead Electrocardiogram Assessments
Summarisation of any abnormal 12-lead ECG findings using descriptive statistics.
Time frame: Baseline, week 2, week 4, month 3, month 6, end-of-study(subject's last visit, 2-48 weeks after study entry)
Population: Analysis of patients in the safety population defined as all patients who had received at least one dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levosimendan | 12-lead Electrocardiogram Assessments | Baseline abnormal ECG | 69 Participants |
| Levosimendan | 12-lead Electrocardiogram Assessments | Week 2 abnormal ECG | 56 Participants |
| Levosimendan | 12-lead Electrocardiogram Assessments | Week 4 abnormal ECG | 43 Participants |
| Levosimendan | 12-lead Electrocardiogram Assessments | Month 3 abnormal ECG | 27 Participants |
| Levosimendan | 12-lead Electrocardiogram Assessments | Month 6 abnormal ECG | 11 Participants |
| Levosimendan | 12-lead Electrocardiogram Assessments | End-of study abnormal ECG | 36 Participants |
Primary
Adverse Events Recording
Adverse Events as subject counts and proportions (%) of subject per Adverse Event
Time frame: From signing informed consent until 14-25 days after the last study treatment for all patients, an average of 23.5 weeks.
Population: Analysis is reported for the safety population which included all subjects receiving any study treatment. Treatment emergent AEs are defined as any event arising or worsening after the start of study treatment until 25 days after the individual subject's last study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Levosimendan | Adverse Events Recording | 161 Participants |
Primary
Pulse/Heart Rate Assessment
Actual values and changes from baseline in supine pre-dose pulse/heart rate were summarised using descriptive statistics .
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)
Population: Analysis was performed on the safety population which included all patients who had received at least one dose of study treatment. The change from baseline in pulse and heart rate was measured at week 2, week 4, week 6 (pulse rate only) Month 3, Month 6 and the individual subject 's last visit in the study. The number of subjects analysed at each timepoint differs from the total number of subjects that entered the study as some study subjects did not undergo the assessment at all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levosimendan | Pulse/Heart Rate Assessment | Change in pulse rate at week 2 | 7.0 beats per minute (bpm) | Standard Deviation 8.8 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in pulse rate at 4 weeks | 10.0 beats per minute (bpm) | Standard Deviation 10.4 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in pulse rate at week 6 | 8.5 beats per minute (bpm) | Standard Deviation 12 |
| Levosimendan | Pulse/Heart Rate Assessment | chnage in pulse rate at Month 3 | 10.4 beats per minute (bpm) | Standard Deviation 10.6 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in pulse rate at month 6 | 12.8 beats per minute (bpm) | Standard Deviation 10.6 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in pulse rate at end-of-study | 3.5 beats per minute (bpm) | Standard Deviation 12.6 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in Heart rate at week 2 | 9.1 beats per minute (bpm) | Standard Deviation 10.1 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in Heart rate at week 4 | 12.8 beats per minute (bpm) | Standard Deviation 9.4 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in heart rate at Month 3 | 12.6 beats per minute (bpm) | Standard Deviation 9.3 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in heart rate at month 6 | 15.0 beats per minute (bpm) | Standard Deviation 9.9 |
| Levosimendan | Pulse/Heart Rate Assessment | Change in heart rate at end-of-study | 5.3 beats per minute (bpm) | Standard Deviation 10.9 |
| Levosimendan | Pulse/Heart Rate Assessment | Baseline supine pulse rate | 75.8 beats per minute (bpm) | Standard Deviation 12.5 |
| Levosimendan | Pulse/Heart Rate Assessment | Baseline supine heart rate | 73.5 beats per minute (bpm) | Standard Deviation 12 |
Secondary
Borg Category Ratio 10 Scale (CR 10)
Patients rated their perception of the severity of their dyspnea using the Borg Category Ration 10 scale (CR 10). The scale ranges from 0(no dysponea) to 10 (maximal dyspnea). each category is numbered and most but not all have verbal cues. At each assessment the patient scored the category they felt best described their symptoms. The analysis measured change from baseline to the end of the study in both a supine and sitting position where a negative score indicates improvement and a positive score reflects worsening.
Time frame: 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)
Population: Analysis was performed on the safety population which included all patients who had received at least one dose of study treatment. The change from baseline in pulse and heart rate was measured at week 2, week 4, week 6 (pulse rate only) Month 3, Month 6 and the individual subject 's last visit in the study. The number of subjects analysed at each timepoint differs from the total number of subjects that entered the study as some study subjects did not undergo the assessment at all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Baseline in Borg score Supine position | 2.52 units on a scale | Standard Deviation 2.62 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score supine at week 2 | 0.15 units on a scale | Standard Deviation 2.16 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | chenge from baseline in Borg score week 4 | 0.40 units on a scale | Standard Deviation 2.21 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score supine at month 3 | 0.54 units on a scale | Standard Deviation 2.05 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score supine at month 6 | 1.61 units on a scale | Standard Deviation 2.07 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score supine at end of study | 1.58 units on a scale | Standard Deviation 2.78 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Baseline Borg score sitting | 2.19 units on a scale | Standard Deviation 2.33 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score sitting at week 2 | 0.01 units on a scale | Standard Deviation 1.71 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score sitting at week 4 | 0.34 units on a scale | Standard Deviation 1.94 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score sitting at month 3 | 0.61 units on a scale | Standard Deviation 2.08 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score sitting month 6 | 1.2 units on a scale | Standard Deviation 1.87 |
| Levosimendan | Borg Category Ratio 10 Scale (CR 10) | Change from baseline in Borg score sitting at end of study | 1.07 units on a scale | Standard Deviation 2.54 |
Secondary
Disease Progression
Count of study withdrawals due to disease progression
Time frame: From Baseline through study completion(subject's last visit, 2-48 weeks after study entry)
Population: Number of study withdrawals due to disease progression were collected for all subjects entered into the study. The study sponsor terminated the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levosimendan | Disease Progression | Total withdrawal due to sponsor terminating the study | 164 Participants |
| Levosimendan | Disease Progression | Number of withdrawals due to disease progression | 30 Participants |
Secondary
Health Care Service Use During the Study (Days Spent in an Institutional Facility)
The number of days spent in an institutional facility were recorded throughout the study using a diary given to the study subjects
Time frame: From baseline to the end of the study(2-48 weeks after study entry)
Population: Analysis performed on the safety population defined as any subject receiving at least one dose of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levosimendan | Health Care Service Use During the Study (Days Spent in an Institutional Facility) | 4.7 days | Standard Deviation 28.2 |
Secondary
Health Care Service Use During the Study(Stays in Hospital)
The number of night stays in hospital were recorded throughout the study using a diary given to the study subjects
Time frame: From baseline to the end of the study(2-48 weeks after study entry)
Population: Analysis performed on the safety population defined as any subject receiving at least one dose of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levosimendan | Health Care Service Use During the Study(Stays in Hospital) | 0.7 Nights | Standard Deviation 2.7 |
Secondary
Health Care Service Use During the Study(Visits to the Emergency Room)
The number of visits to the emergency room were recorded throughout the study using a diary given to the study subjects
Time frame: From baseline to the end of the study(2-48 weeks after study entry)
Population: Analysis performed on the safety population defined as any subject receiving at least one dose of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levosimendan | Health Care Service Use During the Study(Visits to the Emergency Room) | 0.1 visits | Standard Deviation 0.4 |
Secondary
Need for Respiratory Support Device
Time to respiratory device support (non invasive) or death
Time frame: Time to event at study completion (subject's last visit, 2-48 weeks after study entry)
Population: Analyses were performed in the safety population in which all subjects received at least one dose of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Levosimendan | Need for Respiratory Support Device | 259.5 days | Standard Error 10.46 |
Secondary
Number of Subjects Requiring Health and Home Care Resource Use
The number of study subjects requiring Health and home care resource use was aggregated over the course of the study for each subject and summarised using descriptive statistics.
Time frame: Baseline through study completion (2- 48 weeks after study entry)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Levosimendan | Number of Subjects Requiring Health and Home Care Resource Use | 95 Participants |
Secondary
Revised ALS Functional Rating Scale (ALSFRS-R)
ALSFRS-R scale contains 3 parameters related to respiratory function: Severity of dyspnea, occurrence of orthopnea (shortness of breath when in supine position i.e. lying flat), and the use of mechanical ventilation for respiratory in sufficiency. These 3 parameters are combined to create the respiratory domain with a score of 0-12(where 12 is normal function). Although individual items and patients vary, ALSFRS-R typically declines at a relatively constant rate over time. Plotted over time the slope of the line obtained indicates the speed of progression and thus an effective treatment might be expected ro reduce the slope of decline.
Time frame: Change from Baseline in respiratory function of ALSFRS-R at study completion (subject's last visit, 2-48 weeks after study entry)
Population: Analysis was performed on the safety population which included all patients who had received at least one dose of study treatment. The change from baseline in pulse and heart rate was measured at week 2, week 4, week 6 (pulse rate only) Month 3, Month 6 and the individual subject 's last visit in the study. The number of subjects analysed at each timepoint differs from the total number of subjects that entered the study as some study subjects did not undergo the assessment at all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levosimendan | Revised ALS Functional Rating Scale (ALSFRS-R) | Change from baseline in respiratory function ALSFR-S at end of study | -1.2 Score on a scale | Standard Deviation 2.3 |
| Levosimendan | Revised ALS Functional Rating Scale (ALSFRS-R) | Baseline respiratory ALSFRS-R | 9.4 Score on a scale | Standard Deviation 3 |
Secondary
Subject's Status for Tracheostomy and Survival
Number of patients with the need for tracheostomy or who died whilst on treatment from baseline to the end of the study was summarised using descriptive statistics.
Time frame: Baseline to end of study (average 2-48 weeks after study entry
Population: Analysis was performed on the safety population which includes all subjects receiving at least one dose of study treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Levosimendan | Subject's Status for Tracheostomy and Survival | Number of participants who died from baseline to end of the study treatment | 5 Participants |
| Levosimendan | Subject's Status for Tracheostomy and Survival | Number of participants requiring tracheostomy from baseline to the end of the study treatment | 0 Participants |
Secondary
Supine Slow Vital Capacity (SVC)
Change from baseline in supine and sitting SVC (all devices) through to the end of the study, expressed as a % of predicted normal
Time frame: 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)
Population: Analysis was performed on the safety population which included all patients who had received at least one dose of study treatment. The change from baseline in pulse and heart rate was measured at week 2, week 4, week 6 (pulse rate only) Month 3, Month 6 and the individual subject 's last visit in the study. The number of subjects analysed at each timepoint differs from the total number of subjects that entered the study as some study subjects did not undergo the assessment at all timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in supine SVC at the end of the study | -5.6 % of predicted normal | Standard Deviation 17.4 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in supine SVC at week 2 | 1.5 % of predicted normal | Standard Deviation 7.2 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in supine SVC at week 4 | 0.8 % of predicted normal | Standard Deviation 10.2 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in supine SVC at month 3 | -3.5 % of predicted normal | Standard Deviation 10.4 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in supine SVC at month 6 | -5.3 % of predicted normal | Standard Deviation 13.2 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in sitting SVC at week 2 | 1.4 % of predicted normal | Standard Deviation 6.6 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in sitting SVC at week 4 | 2.1 % of predicted normal | Standard Deviation 9.8 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in sitting SVC month 3 | -1.9 % of predicted normal | Standard Deviation 11.9 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in sitting SVC month 6 | -6.1 % of predicted normal | Standard Deviation 12.4 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Change from baseline in sitting SVC at the end of the study | -7.3 % of predicted normal | Standard Deviation 12.1 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Baseline Supine SVC (% predicted normal | 54.4 % of predicted normal | Standard Deviation 21.6 |
| Levosimendan | Supine Slow Vital Capacity (SVC) | Baseline Sitting SVC (% predicted normal) | 61.4 % of predicted normal | Standard Deviation 19.4 |