Trial Outcomes & Findings for Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension (NCT NCT03948178)
NCT ID: NCT03948178
Last Updated: 2023-03-09
Results Overview
Adverse Events as subject counts and proportions (%) of subject per Adverse Event
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
227 participants
Primary outcome timeframe
From signing informed consent until 14-25 days after the last study treatment for all patients, an average of 23.5 weeks.
Results posted on
2023-03-09
Participant Flow
Patients with amyotrophic lateral sclerosis (ALS) who completed 48 weeks of treatment in the REFALS study (NCT03505021) were recruited
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.
Participant milestones
| Measure |
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
|
|---|---|
|
Overall Study
STARTED
|
227
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
227
|
Reasons for withdrawal
| Measure |
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
|
|---|---|
|
Overall Study
Protocol Violation
|
1
|
|
Overall Study
Lost to Follow-up
|
2
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Reason not known
|
2
|
|
Overall Study
Personal reason
|
14
|
|
Overall Study
Disease progression
|
30
|
|
Overall Study
Adverse Event
|
12
|
|
Overall Study
Sponsor terminated study
|
164
|
Baseline Characteristics
Effects of Oral Levosimendan on Respiratory Function in Patients With Amyotrophic Lateral Sclerosis (ALS): Open-Label Extension
Baseline characteristics by cohort
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
160 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
67 Participants
n=93 Participants
|
|
Sex: Female, Male
Female
|
85 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
142 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
224 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
218 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
9 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 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.
Adverse Events as subject counts and proportions (%) of subject per Adverse Event
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Adverse Events Recording
|
161 Participants
|
PRIMARY outcome
Timeframe: 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.
Actual values and changes from baseline in supine pre-dose pulse/heart rate were summarised using descriptive statistics .
Outcome measures
| Measure |
Levosimendan
n=224 Participants
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
|
|---|---|
|
Pulse/Heart Rate Assessment
Change in pulse rate at week 2
|
7.0 beats per minute (bpm)
Standard Deviation 8.8
|
|
Pulse/Heart Rate Assessment
Change in pulse rate at 4 weeks
|
10.0 beats per minute (bpm)
Standard Deviation 10.4
|
|
Pulse/Heart Rate Assessment
Change in pulse rate at week 6
|
8.5 beats per minute (bpm)
Standard Deviation 12.0
|
|
Pulse/Heart Rate Assessment
chnage in pulse rate at Month 3
|
10.4 beats per minute (bpm)
Standard Deviation 10.6
|
|
Pulse/Heart Rate Assessment
Change in pulse rate at month 6
|
12.8 beats per minute (bpm)
Standard Deviation 10.6
|
|
Pulse/Heart Rate Assessment
Change in pulse rate at end-of-study
|
3.5 beats per minute (bpm)
Standard Deviation 12.6
|
|
Pulse/Heart Rate Assessment
Change in Heart rate at week 2
|
9.1 beats per minute (bpm)
Standard Deviation 10.1
|
|
Pulse/Heart Rate Assessment
Change in Heart rate at week 4
|
12.8 beats per minute (bpm)
Standard Deviation 9.4
|
|
Pulse/Heart Rate Assessment
Change in heart rate at Month 3
|
12.6 beats per minute (bpm)
Standard Deviation 9.3
|
|
Pulse/Heart Rate Assessment
Change in heart rate at month 6
|
15.0 beats per minute (bpm)
Standard Deviation 9.9
|
|
Pulse/Heart Rate Assessment
Change in heart rate at end-of-study
|
5.3 beats per minute (bpm)
Standard Deviation 10.9
|
|
Pulse/Heart Rate Assessment
Baseline supine pulse rate
|
75.8 beats per minute (bpm)
Standard Deviation 12.5
|
|
Pulse/Heart Rate Assessment
Baseline supine heart rate
|
73.5 beats per minute (bpm)
Standard Deviation 12.0
|
PRIMARY outcome
Timeframe: 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
Summarisation of any abnormal 12-lead ECG findings using descriptive statistics.
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
12-lead Electrocardiogram Assessments
Baseline abnormal ECG
|
69 Participants
|
|
12-lead Electrocardiogram Assessments
Week 2 abnormal ECG
|
56 Participants
|
|
12-lead Electrocardiogram Assessments
Week 4 abnormal ECG
|
43 Participants
|
|
12-lead Electrocardiogram Assessments
Month 3 abnormal ECG
|
27 Participants
|
|
12-lead Electrocardiogram Assessments
Month 6 abnormal ECG
|
11 Participants
|
|
12-lead Electrocardiogram Assessments
End-of study abnormal ECG
|
36 Participants
|
SECONDARY outcome
Timeframe: 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.
Count of study withdrawals due to disease progression
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Disease Progression
Total withdrawal due to sponsor terminating the study
|
164 Participants
|
|
Disease Progression
Number of withdrawals due to disease progression
|
30 Participants
|
SECONDARY outcome
Timeframe: 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.
Change from baseline in supine and sitting SVC (all devices) through to the end of the study, expressed as a % of predicted normal
Outcome measures
| Measure |
Levosimendan
n=185 Participants
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
|
|---|---|
|
Supine Slow Vital Capacity (SVC)
Change from baseline in supine SVC at week 2
|
1.5 % of predicted normal
Standard Deviation 7.2
|
|
Supine Slow Vital Capacity (SVC)
Change from baseline in supine SVC at week 4
|
0.8 % of predicted normal
Standard Deviation 10.2
|
|
Supine Slow Vital Capacity (SVC)
Change from baseline in supine SVC at month 3
|
-3.5 % of predicted normal
Standard Deviation 10.4
|
|
Supine Slow Vital Capacity (SVC)
Change from baseline in supine SVC at month 6
|
-5.3 % of predicted normal
Standard Deviation 13.2
|
|
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
|
|
Supine Slow Vital Capacity (SVC)
Change from baseline in sitting SVC at week 2
|
1.4 % of predicted normal
Standard Deviation 6.6
|
|
Supine Slow Vital Capacity (SVC)
Change from baseline in sitting SVC at week 4
|
2.1 % of predicted normal
Standard Deviation 9.8
|
|
Supine Slow Vital Capacity (SVC)
Change from baseline in sitting SVC month 3
|
-1.9 % of predicted normal
Standard Deviation 11.9
|
|
Supine Slow Vital Capacity (SVC)
Change from baseline in sitting SVC month 6
|
-6.1 % of predicted normal
Standard Deviation 12.4
|
|
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
|
|
Supine Slow Vital Capacity (SVC)
Baseline Supine SVC (% predicted normal
|
54.4 % of predicted normal
Standard Deviation 21.6
|
|
Supine Slow Vital Capacity (SVC)
Baseline Sitting SVC (% predicted normal)
|
61.4 % of predicted normal
Standard Deviation 19.4
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Levosimendan
n=226 Participants
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
|
|---|---|
|
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
|
|
Revised ALS Functional Rating Scale (ALSFRS-R)
Baseline respiratory ALSFRS-R
|
9.4 Score on a scale
Standard Deviation 3.0
|
SECONDARY outcome
Timeframe: 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
Time to respiratory device support (non invasive) or death
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Need for Respiratory Support Device
|
259.5 days
Standard Error 10.46
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Levosimendan
n=203 Participants
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
|
|---|---|
|
Borg Category Ratio 10 Scale (CR 10)
Baseline in Borg score Supine position
|
2.52 units on a scale
Standard Deviation 2.62
|
|
Borg Category Ratio 10 Scale (CR 10)
Baseline Borg score sitting
|
2.19 units on a scale
Standard Deviation 2.33
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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
|
|
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 outcome
Timeframe: 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.
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Number of Subjects Requiring Health and Home Care Resource Use
|
95 Participants
|
SECONDARY outcome
Timeframe: Baseline to end of study (average 2-48 weeks after study entryPopulation: Analysis was performed on the safety population which includes all subjects receiving at least one dose of study treatment
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.
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Subject's Status for Tracheostomy and Survival
Number of participants who died from baseline to end of the study treatment
|
5 Participants
|
|
Subject's Status for Tracheostomy and Survival
Number of participants requiring tracheostomy from baseline to the end of the study treatment
|
0 Participants
|
SECONDARY outcome
Timeframe: 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
The number of night stays in hospital were recorded throughout the study using a diary given to the study subjects
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Health Care Service Use During the Study(Stays in Hospital)
|
0.7 Nights
Standard Deviation 2.7
|
SECONDARY outcome
Timeframe: 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
The number of visits to the emergency room were recorded throughout the study using a diary given to the study subjects
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Health Care Service Use During the Study(Visits to the Emergency Room)
|
0.1 visits
Standard Deviation 0.4
|
SECONDARY outcome
Timeframe: 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
The number of days spent in an institutional facility were recorded throughout the study using a diary given to the study subjects
Outcome measures
| Measure |
Levosimendan
n=227 Participants
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
|
|---|---|
|
Health Care Service Use During the Study (Days Spent in an Institutional Facility)
|
4.7 days
Standard Deviation 28.2
|
Adverse Events
Levosimendan
Serious events: 44 serious events
Other events: 215 other events
Deaths: 19 deaths
Serious adverse events
| Measure |
Levosimendan
n=227 participants at risk
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
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.8%
11/227 • Number of events 11 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Choking
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Dysponea
|
0.88%
2/227 • Number of events 2 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory arrest
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory depression
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Infections and infestations
Pneumonia
|
1.8%
4/227 • Number of events 5 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Infections and infestations
Urinary Tract Infection
|
0.88%
2/227 • Number of events 2 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Infections and infestations
Cystitis bacterial
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Infections and infestations
Systemic Viral Infection
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Infections and infestations
Urosepsis
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Infections and infestations
Cellulitis
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Diarrhoea
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Dysphagia
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Intestinal Obstruction
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Lower Intestinal Hemorrhage
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Saliva altered
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Constipation
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Injury, poisoning and procedural complications
Stoma Site Pain
|
0.88%
2/227 • Number of events 2 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Injury, poisoning and procedural complications
Fall
|
0.88%
2/227 • Number of events 2 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Injury, poisoning and procedural complications
Subdural Hematoma
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Injury, poisoning and procedural complications
Humerus Fracture
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Injury, poisoning and procedural complications
Meniscus Injury
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Cardiac disorders
Cardiac Failure
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Cardiac disorders
Supraventricular Tachycardia
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Cardiac disorders
Cardiac Arrest
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
General disorders
Chest Pain
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
General disorders
Pyrexia
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
General disorders
Euthanesia
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Metabolism and nutrition disorders
Back Pain
|
0.88%
2/227 • Number of events 2 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive Ductal Breast Carcinoma
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastasis to lymph nodes
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Renal and urinary disorders
Haematuria
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Renal and urinary disorders
Renal Mass
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Psychiatric disorders
Suicide Attempt
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Investigations
Oxygen Saturation decreased
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.44%
1/227 • Number of events 1 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
Other adverse events
| Measure |
Levosimendan
n=227 participants at risk
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
|
|---|---|
|
Injury, poisoning and procedural complications
Fall
|
11.0%
25/227 • Number of events 42 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Nervous system disorders
Headache
|
8.8%
20/227 • Number of events 28 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Cardiac disorders
Tachycardia
|
7.9%
18/227 • Number of events 20 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Dysponea
|
6.2%
14/227 • Number of events 15 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
5.7%
13/227 • Number of events 13 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Investigations
Heart Rate Increased
|
5.3%
12/227 • Number of events 12 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Dysphagia
|
4.8%
11/227 • Number of events 11 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Constipation
|
4.4%
10/227 • Number of events 11 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Infections and infestations
Nasopharyngitis
|
4.4%
10/227 • Number of events 11 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Diarrhoea
|
4.0%
9/227 • Number of events 9 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.5%
8/227 • Number of events 8 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Infections and infestations
Urinary Tract Infection
|
3.5%
8/227 • Number of events 9 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
General disorders
Oedema peripheral
|
3.1%
7/227 • Number of events 8 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Respiratory, thoracic and mediastinal disorders
Hypoventilation
|
2.6%
6/227 • Number of events 7 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
2.6%
6/227 • Number of events 7 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Injury, poisoning and procedural complications
Skin Laceration
|
2.6%
6/227 • Number of events 7 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
2.2%
5/227 • Number of events 7 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Psychiatric disorders
Insomnia
|
2.2%
5/227 • Number of events 5 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Psychiatric disorders
Anxiety
|
2.6%
6/227 • Number of events 6 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Nervous system disorders
Dizziness
|
2.6%
6/227 • Number of events 7 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
General disorders
Pyrexia
|
2.2%
5/227 • Number of events 6 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
|
Gastrointestinal disorders
Vomiting
|
2.2%
5/227 • Number of events 5 • From signing informed consent until 14-25 days after the last study treatment administration, an average of 23.5 weeks.
Four enrolled subjects did not start study treatment and are excluded from the safety population
|
Additional Information
Head of Compliance and UK Study Management, Clinical Operations
Orion Corporation
Phone: +441159487100
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place