Trial Outcomes & Findings for CORAL - Cebranopadol Versus Morphine Prolonged-release in Patients With Chronic Moderate to Severe Pain Related to Cancer (NCT NCT01964378)
NCT ID: NCT01964378
Last Updated: 2021-07-15
Results Overview
Morphine sulfate immediate release (IR) 10 mg tablets were supplied as rescue medication to trial participants. No dose adjustments of the morphine prolonged release or cebranopadol were allowed during the maintenance period. The daily use of morphine sulfate 10 mg IR tablets was documented by each participant in the trial. The total daily amount of morphine IR was subject to an upper limit recommendation. The primary endpoint is the average amount of daily rescue medication intake over the last 2 weeks of the maintenance period.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
200 participants
Primary outcome timeframe
The last 2 weeks of the expected 6-week treatment period.
Results posted on
2021-07-15
Participant Flow
The trial started on 29 Oct 2013 with the enrollment of the first subject and was completed on 16 Oct 2015 when the last subject completed the last follow-up examination.
200 Participants were enrolled (signed consent): enrollment failures did not meet inclusion or met exclusion criteria (62 participants), died (1), withdrew consent (4), or met other reasons (1). 132 Participants were allocated to treatment and 126 were dosed (Safety Set).
Participant milestones
| Measure |
Cebranopadol
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Overall Study
STARTED
|
66
|
66
|
|
Overall Study
Participants Treated (Safety Set)
|
65
|
61
|
|
Overall Study
COMPLETED
|
41
|
45
|
|
Overall Study
NOT COMPLETED
|
25
|
21
|
Reasons for withdrawal
| Measure |
Cebranopadol
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Overall Study
Disc. due to death before first dosing
|
0
|
1
|
|
Overall Study
Disc. due to AE before first dosing
|
1
|
0
|
|
Overall Study
Death
|
3
|
2
|
|
Overall Study
Adverse Event
|
12
|
5
|
|
Overall Study
Lack of Efficacy
|
0
|
1
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
7
|
5
|
|
Overall Study
Inclusion/exclusion criteria not met
|
1
|
3
|
|
Overall Study
Other
|
1
|
2
|
Baseline Characteristics
CORAL - Cebranopadol Versus Morphine Prolonged-release in Patients With Chronic Moderate to Severe Pain Related to Cancer
Baseline characteristics by cohort
| Measure |
Cebranopadol
n=65 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
Total
n=126 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
36 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
29 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Age, Continuous
|
63.8 years
STANDARD_DEVIATION 9.18 • n=5 Participants
|
61 years
STANDARD_DEVIATION 10.64 • n=7 Participants
|
62.4 years
STANDARD_DEVIATION 9.98 • n=5 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
49 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
77 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
58 Participants
n=5 Participants
|
60 Participants
n=7 Participants
|
118 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
65 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
126 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Romania
|
2 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Hungary
|
4 participants
n=5 Participants
|
5 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Austria
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
4 participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
16 participants
n=5 Participants
|
16 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Region of Enrollment
Slovakia
|
13 participants
n=5 Participants
|
13 participants
n=7 Participants
|
26 participants
n=5 Participants
|
|
Region of Enrollment
Bulgaria
|
7 participants
n=5 Participants
|
4 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
Chile
|
2 participants
n=5 Participants
|
0 participants
n=7 Participants
|
2 participants
n=5 Participants
|
|
Region of Enrollment
Serbia
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
13 participants
n=5 Participants
|
14 participants
n=7 Participants
|
27 participants
n=5 Participants
|
|
Region of Enrollment
Croatia
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Prior opioid treatment
WHO Step II analgesic
|
27 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Prior opioid treatment
WHO Step III analgesic excluding morphine
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
|
Prior opioid treatment
Morphine
|
16 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
ECOG Status
Status 0
|
17 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
ECOG Status
Status 1
|
30 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
ECOG Status
Status 2
|
18 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
ECOG Status
Status 3
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
ECOG Status
Status 4
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
ECOG Status
Status 5
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Cancer history - Stage IV
Stage IV
|
52 Participants
n=5 Participants
|
45 Participants
n=7 Participants
|
97 Participants
n=5 Participants
|
|
Cancer history - Stage IV
Other
|
13 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Participants with a neuropathic pain component
Neuropathic component present
|
28 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Participants with a neuropathic pain component
No neuropathic component present
|
37 Participants
n=5 Participants
|
37 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Participants with a visceral pain component
Visceral pain present
|
31 Participants
n=5 Participants
|
28 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
|
Participants with a visceral pain component
No visceral pain present
|
34 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
|
Participants with a somatic pain component
Somatic pain component present
|
39 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Participants with a somatic pain component
No somatic pain component present
|
26 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
53 Participants
n=5 Participants
|
|
Height
|
1.6889 meter
STANDARD_DEVIATION 0.09097 • n=5 Participants
|
1.692 meter
STANDARD_DEVIATION 0.07952 • n=7 Participants
|
1.6904 meter
STANDARD_DEVIATION 0.08529 • n=5 Participants
|
|
Weight
|
73.52 kilogram(s)
STANDARD_DEVIATION 14.126 • n=5 Participants
|
71.23 kilogram(s)
STANDARD_DEVIATION 12.807 • n=7 Participants
|
72.41 kilogram(s)
STANDARD_DEVIATION 13.499 • n=5 Participants
|
|
Body Mass Index (BMI)
|
25.74 kilogram(s)/square meter
STANDARD_DEVIATION 4.39 • n=5 Participants
|
24.84 kilogram(s)/square meter
STANDARD_DEVIATION 4.022 • n=7 Participants
|
25.31 kilogram(s)/square meter
STANDARD_DEVIATION 4.223 • n=5 Participants
|
|
Baseline pain intensity
|
6.23 units on a scale
STANDARD_DEVIATION 1.000 • n=5 Participants
|
6.30 units on a scale
STANDARD_DEVIATION 1.230 • n=7 Participants
|
6.26 units on a scale
STANDARD_DEVIATION 1.114 • n=5 Participants
|
|
Worst daily pain intensity
|
7.27 units on a scale
STANDARD_DEVIATION 1.222 • n=5 Participants
|
7.29 units on a scale
STANDARD_DEVIATION 1.117 • n=7 Participants
|
7.28 units on a scale
STANDARD_DEVIATION 1.168 • n=5 Participants
|
|
Time since cancer pain onset
|
62.25 weeks
STANDARD_DEVIATION 111.915 • n=5 Participants
|
60.22 weeks
STANDARD_DEVIATION 79.792 • n=7 Participants
|
61.27 weeks
STANDARD_DEVIATION 97.313 • n=5 Participants
|
PRIMARY outcome
Timeframe: The last 2 weeks of the expected 6-week treatment period.Population: The Per Protocol Set (PPS) describes a subset of subjects in the Full Analysis Set (FAS). The PPS included all allocated participants who completed at least 2 weeks of treatment in the maintenance phase and had no major protocol deviations relevant for efficacy evaluations.
Morphine sulfate immediate release (IR) 10 mg tablets were supplied as rescue medication to trial participants. No dose adjustments of the morphine prolonged release or cebranopadol were allowed during the maintenance period. The daily use of morphine sulfate 10 mg IR tablets was documented by each participant in the trial. The total daily amount of morphine IR was subject to an upper limit recommendation. The primary endpoint is the average amount of daily rescue medication intake over the last 2 weeks of the maintenance period.
Outcome measures
| Measure |
Cebranopadol
n=43 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=45 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Average Amount of Daily Rescue Medication at the End of the Maintenance Period (Per Protocol Set)
|
4.25 milligram(s)/24 hours
Standard Error 1.7
|
8.92 milligram(s)/24 hours
Standard Error 1.72
|
PRIMARY outcome
Timeframe: The last 2 weeks of the expected 6-week treatment period.Population: The Full Analysis Set includes all allocated participants who took at least 1 dose of the investigational medicinal product (IMP) and had at least 1 day with information for the amount of rescue medication intake after the first intake of double-blind IMP (study drug).
Morphine sulfate IR 10 mg tablets were supplied as rescue medication to trial participants. No dose adjustments of the morphine prolonged release or cebranopadol were allowed during the maintenance period. The daily use of morphine sulfate 10 mg IR tablets was documented by each participant in the trial. The total daily amount of morphine IR was subject to an upper limit recommendation. The primary endpoint is the average amount of daily rescue medication intake over the last 2 weeks of the maintenance period.
Outcome measures
| Measure |
Cebranopadol
n=64 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Average Amount of Daily Rescue Medication at the End of the Maintenance Period (Full Analysis Set)
|
3.46 milligram(s)/24 hours
Standard Error 1.71
|
10.94 milligram(s)/24 hours
Standard Error 1.75
|
SECONDARY outcome
Timeframe: The last 2 weeks of the expected 6-week treatment period.Population: Full Analysis Set (FAS). Clinically relevant pain reduction (Yes/No) in Maintenance Week 3 and Week 4. Missing data were imputed using a multiple imputation on the weekly average pain intensity. Participants that discontinued from the trial due to a lack of efficacy were classified as non-responders.
Each participant indicated the level of pain on an 11-point numerical rating scale (NRS), where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The participants entered their pain intensity in their diary on a daily basis. The pain intensity score in the 2 weeks prior to the final evaluation in the maintenance period was compared with the baseline, the baseline pain intensity was calculated based on the 3 days prior to treatment allocation. The definition of a clinically relevant pain reduction (yes/no) was the presence of at least 1 of the 3 following conditions: * Average pain intensity (i.e., average of the 24-hour pain intensities over the last 2 weeks of the Maintenance Phase) of less than 4 points on the 11-point NRS, or * Reduction in average pain intensity by at least 30% (compared to the baseline assessment), or * Reduction in average pain intensity by at least 2 points (compared to the baseline assessment).
Outcome measures
| Measure |
Cebranopadol
n=64 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Proportion of Participants With Clinically Relevant Pain Reduction at the End of the Maintenance Period
Clinically relevant pain reduction (Yes)
|
48 Participants
|
51 Participants
|
|
Proportion of Participants With Clinically Relevant Pain Reduction at the End of the Maintenance Period
Clinically relevant pain reduction (No)
|
16 Participants
|
10 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; last 2 weeks of the expected 6-week treatment periodPopulation: Full Analysis Set (FAS)
Participants will be asked: "Please rate your pain by selecting the one number that best describes your pain on average during the last 24 hours." every day in the morning. They will score their pain intensity on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The weekly mean value of the 24-h average pain intensity will be calculated as a mean score of these daily entries of average pain intensity for each trial week.
Outcome measures
| Measure |
Cebranopadol
n=64 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Change in Weekly Mean of the Daily Average Pain Intensity Score From Baseline
|
-3.4 units on a scale
Standard Deviation 2.11
|
-3.2 units on a scale
Standard Deviation 1.60
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; last 2 weeks of the expected 6-week treatment periodPopulation: Full Analysis Set (FAS). Worsening in 24-hour pain or premature discontinuation due to lack of efficacy or Adverse Event was regarded a non-response, other missing data is imputed using last observation carried forward (LOCF).
Pain intensity will be recorded daily by each participant in the morning on an 11-point Numerical Rating Scale, ranging from 0 (no pain) to 10 (worst imaginable pain). From this, the weekly average 24-hour pain intensity will be calculated. The number of participants with a 0, 10, 20, 30, up to a 100% reduction in weekly mean pain intensity will be reported over each week and over the last 2 weeks of the maintenance period.
Outcome measures
| Measure |
Cebranopadol
n=64 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Response Rate to Treatment
Non-responder
|
13 Participants
|
9 Participants
|
|
Response Rate to Treatment
>= 0% pain reduction
|
51 Participants
|
52 Participants
|
|
Response Rate to Treatment
>= 10% pain reduction
|
50 Participants
|
52 Participants
|
|
Response Rate to Treatment
>= 20% pain reduction
|
44 Participants
|
50 Participants
|
|
Response Rate to Treatment
>= 30% pain reduction
|
39 Participants
|
42 Participants
|
|
Response Rate to Treatment
>= 40% pain reduction
|
31 Participants
|
37 Participants
|
|
Response Rate to Treatment
>= 50% pain reduction
|
26 Participants
|
27 Participants
|
|
Response Rate to Treatment
>= 60% pain reduction
|
19 Participants
|
18 Participants
|
|
Response Rate to Treatment
>= 70% pain reduction
|
13 Participants
|
11 Participants
|
|
Response Rate to Treatment
>= 80% pain reduction
|
10 Participants
|
8 Participants
|
|
Response Rate to Treatment
>= 90% pain reduction
|
5 Participants
|
2 Participants
|
|
Response Rate to Treatment
100% pain reduction
|
3 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (Week 6)Population: Subset of participants that were assessed to have Neuropathic Pain (using the DN4 questionnaire) at baseline.
Participants with neuropathic pain (determined by the completion of the Douleur Neuropathique En 4 Questions \[DN4\] questionnaire at allocation) rated their symptoms of neuropathic pain on the Neuropathic Pain Symptom Inventory (NPSI). Ten out of 12 questions were answered on an 11-point scale 0 (no symptom present) to 10 (worst imaginable); 2 out of 12 questions assessed the duration of spontaneous pain and the number of pain attacks and were answered by selecting 1 of 5 possible responses. Mean scores of NPSI were calculated. The overall NPSI score was calculated by the summation of all responses in the ranges between 0 (all symptoms absent) and 1 (all symptoms present and at the worst intensity). A negative change indicates that the intensity of all the neuropathic symptom components have decreased since the start of treatment.
Outcome measures
| Measure |
Cebranopadol
n=11 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=17 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Overall Score of the Neuropathic Pain Symptom Inventory (NPSI)
|
-0.15 units on a scale
Standard Deviation 0.126
|
-0.10 units on a scale
Standard Deviation 0.129
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (6 weeks)Population: Full Analysis Set; means (standard deviations) are presented for the number of participants at the End-of-Treatment Visit with respective data available.
The EuroQol-5 Dimension Health Questionnaire is a generic health related quality of life instrument. The participants will answer 5 questions on 5 dimensions of their health related quality of life: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each question has 3 possible answers reflecting 3 levels of impact on the quality of life. The weighted EQ-5D health status index values are derived and reported as change from baseline. The responses to the 5 EQ-5D dimensions were scored using a utility-weighted algorithm to derive an EQ-5D health status index score (with 1 indicating "full health" and 0 representing "dead"). The higher the values (the closer the value is to 1) the better the health status in a treatment group. A positive change indicates an improvement.
Outcome measures
| Measure |
Cebranopadol
n=49 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=52 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
EuroQol-5 Dimension (EQ-5D) Health Questionnaire: Weighted EQ-5D Health Status Index
|
0.1 units on a scale
Standard Deviation 0.331
|
0.2 units on a scale
Standard Deviation 0.287
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (6 weeks)Population: Full Analysis Set; means (standard deviations) are presented for the number of participants at the End-of-Treatment Visit with respective data available.
The EuroQol-5 Dimension Health Questionnaire is a generic health related quality of life instrument. EuroQoL-5D Health State Visual Analog Scale (VAS) is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. The values indicated represent the change from the baseline, a positive value indicates an improvement.
Outcome measures
| Measure |
Cebranopadol
n=47 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=52 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
EuroQol-5 Dimension (EQ-5D) Health Questionnaire: Visual Analog Scale (VAS) Score
|
-0.1 units on a scale
Standard Deviation 22.983
|
15.1 units on a scale
Standard Deviation 24.305
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (6 weeks)Population: Full Analysis Set (FAS). End of Treatment (End of Maintenance Period Visit).
The Physical and Mental Component Scores are calculated from the responses by participants to 12 questions. These 12 questions cover 8 domains, (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role participation with emotional health problems, and mental health) that a participant was asked to rate over the last week. Questions are scored on a Likert-scale. The Physical and Mental Component Scores were not derived as the trial was terminated. Changes in the individual item scores are therefore reported. A higher score indicates a better participant perceived state of health. All domains were scored on a scale from 0 (lowest level of health) to 100 (highest level of health), with 100 representing the best possible health state. If the values are positive there was an improvement. The higher the value the greater the improvement.
Outcome measures
| Measure |
Cebranopadol
n=64 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Change in the Physical and Mental Component Scores From the Short Form 12® Health Survey (SF-12)
Role physical
|
5.1 units on a scale
Standard Deviation 27.23
|
6.4 units on a scale
Standard Deviation 24.10
|
|
Change in the Physical and Mental Component Scores From the Short Form 12® Health Survey (SF-12)
Social function
|
7.1 units on a scale
Standard Deviation 28.87
|
5.2 units on a scale
Standard Deviation 33.38
|
|
Change in the Physical and Mental Component Scores From the Short Form 12® Health Survey (SF-12)
Role emotional
|
3.3 units on a scale
Standard Deviation 28.39
|
0.2 units on a scale
Standard Deviation 27.57
|
|
Change in the Physical and Mental Component Scores From the Short Form 12® Health Survey (SF-12)
Mental health
|
3.1 units on a scale
Standard Deviation 20.18
|
6.1 units on a scale
Standard Deviation 21.32
|
|
Change in the Physical and Mental Component Scores From the Short Form 12® Health Survey (SF-12)
Physical function
|
7.1 units on a scale
Standard Deviation 31.04
|
9.9 units on a scale
Standard Deviation 24.68
|
|
Change in the Physical and Mental Component Scores From the Short Form 12® Health Survey (SF-12)
Bodily pain
|
10.2 units on a scale
Standard Deviation 29.28
|
9.0 units on a scale
Standard Deviation 31.43
|
|
Change in the Physical and Mental Component Scores From the Short Form 12® Health Survey (SF-12)
General health
|
5.4 units on a scale
Standard Deviation 20.13
|
9.2 units on a scale
Standard Deviation 27.38
|
|
Change in the Physical and Mental Component Scores From the Short Form 12® Health Survey (SF-12)
Vitality
|
0.0 units on a scale
Standard Deviation 25.00
|
10.4 units on a scale
Standard Deviation 28.77
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (6 weeks)Population: Full Analysis Set (FAS). End of Treatment (End of Maintenance Period Visit). Participants with data available.
In the Patient Global Impression of Change (PGIC) the participant indicates the perceived change over the treatment period compared to his condition prior to the start of treatment. The participant is requested to choose one of seven categories. Scores range from very much improved to very much worse.
Outcome measures
| Measure |
Cebranopadol
n=56 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=56 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Patient Global Impression of Change (PGIC)
Very much improved
|
5 Participants
|
3 Participants
|
|
Patient Global Impression of Change (PGIC)
Much improved
|
18 Participants
|
17 Participants
|
|
Patient Global Impression of Change (PGIC)
Minimally improved
|
17 Participants
|
17 Participants
|
|
Patient Global Impression of Change (PGIC)
No change
|
4 Participants
|
10 Participants
|
|
Patient Global Impression of Change (PGIC)
Minimally worse
|
4 Participants
|
4 Participants
|
|
Patient Global Impression of Change (PGIC)
Much worse
|
2 Participants
|
2 Participants
|
|
Patient Global Impression of Change (PGIC)
Very much worse
|
0 Participants
|
0 Participants
|
|
Patient Global Impression of Change (PGIC)
Missing
|
6 Participants
|
3 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (6 weeks)Population: Full Analysis Set (FAS). End of Treatment (End of Maintenance Period Visit). Participants with data available.
In the Clinical Global Impression of Change (CGIC) the clinician indicates the perceived change in patient's condition over the treatment period as compared to patient's condition prior to the start of treatment. The clinician is requested to choose one of seven categories. Scores range from very much improved to very much worse.
Outcome measures
| Measure |
Cebranopadol
n=56 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=56 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Clinical Global Impression of Change (CGIC)
Very much improved
|
8 Participants
|
4 Participants
|
|
Clinical Global Impression of Change (CGIC)
Much worse
|
2 Participants
|
1 Participants
|
|
Clinical Global Impression of Change (CGIC)
Very much worse
|
0 Participants
|
2 Participants
|
|
Clinical Global Impression of Change (CGIC)
Missing
|
6 Participants
|
3 Participants
|
|
Clinical Global Impression of Change (CGIC)
Much improved
|
20 Participants
|
26 Participants
|
|
Clinical Global Impression of Change (CGIC)
Minimally improved
|
10 Participants
|
9 Participants
|
|
Clinical Global Impression of Change (CGIC)
No change
|
7 Participants
|
5 Participants
|
|
Clinical Global Impression of Change (CGIC)
Minimally worse
|
3 Participants
|
6 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (6 weeks)Population: Safety Set; number of participants with data available.
The PAC-SYM is a 12-item self-administered questionnaire that assesses the severity of constipation-related symptoms during past 2 weeks. Items are rated on a 5-point Likert scale, where 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe.The PAC-SYM contains 3 subscales: stool symptoms (5 items), abdominal symptoms (4 items), rectal symptoms (3 items). If at least 6 items are assessed, the PAC-SYM overall score is calculated as the sum of the scores of all non-missing items divided by number of non-missing items. The minimum overall score is 0, the maximum overall score is 4. If more than 6 items are missing, no overall score is calculated. Changes from baseline for the overall score are presented. If the changes in the overall (or subscale) scores are positive then there is a worsening in symptoms associated with constipation.
Outcome measures
| Measure |
Cebranopadol
n=49 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=53 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Overall Score of the Patient Assessment of Constipation Symptoms (PAC-SYM)
|
0.07 units on a scale
Standard Deviation 0.536
|
0.07 units on a scale
Standard Deviation 0.632
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (6 weeks)Population: Full analysis set (FAS)
Participants will be asked: "Please rate your pain by selecting the one number that best describes your pain at its worst during the last 24 hours." every day in the morning. They will score their pain intensity on an 11-point Numerical Rating Scale (NRS) where a score of 0 indicated "no pain" and a score of 10 indicated "pain as bad as you can imagine". The weekly mean value of the 24 h worst pain intensity will be calculated as a mean score of these daily entries of worst pain intensity for each trial week. A positive change from baseline will indicate a worsening, whilst a negative change will indicate an improvement of pain.
Outcome measures
| Measure |
Cebranopadol
n=64 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Change in Weekly Mean of the Daily Worst Pain Intensity Score From Baseline
|
-3.3 units on a scale
Standard Deviation 2.68
|
-3.3 units on a scale
Standard Deviation 2.11
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline; End-of-Treatment Visit (6 weeks)Population: Full Analysis Set
The CPSI measures 5 items on 100-mm visual analog scales: trouble falling asleep (CPSI1), needing sleep medication (CPSI2), awakened by pain during the night (CPSI3) and in the morning (CPSI4) \[all with anchors for 0 = never and 100 = always\], and overall quality of sleep (CPSI5) \[with anchors of 0 = very poor and 100 = excellent\]. The sleep problem index is the sum of items CPSI1, CPSI3 and CPSI4. The minimum sleep problem index is 0 mm, the maximum 300 mm, the higher the worse. For the overall quality of sleep, minimum and maximum are 0 and 100 mm, the higher the better. A decrease in the sleep problem index indicates an improvement as does an increase in the overall quality of sleep. Changes from baseline to the End-of-Treatment Visit of the Maintenance Phase (scheduled for Week 6) were calculated.
Outcome measures
| Measure |
Cebranopadol
n=64 Participants
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 Participants
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Change From Baseline to End-of-Treatment Visit in Chronic Pain Sleep Inventory (CPSI) Scores
Sleep Problem Index
|
-62.7 units on a scale
Standard Deviation 77.91
|
-53.7 units on a scale
Standard Deviation 77.71
|
|
Change From Baseline to End-of-Treatment Visit in Chronic Pain Sleep Inventory (CPSI) Scores
Overall Quality of Sleep
|
20.5 units on a scale
Standard Deviation 36.11
|
8.1 units on a scale
Standard Deviation 30.4
|
Adverse Events
Cebranopadol
Serious events: 14 serious events
Other events: 52 other events
Deaths: 3 deaths
Morphine Prolonged Release
Serious events: 11 serious events
Other events: 48 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Cebranopadol
n=65 participants at risk
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 participants at risk
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
7.7%
5/65 • Number of events 5 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
11.5%
7/61 • Number of events 7 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Cardiac disorders
Myocardial infarction
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract haemorrhage
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Nervous system disorders
Hemiparesis
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
General disorders
Asthenia
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Gastrointestinal disorders
Vomiting
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Musculoskeletal and connective tissue disorders
Pathological fracture
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Metabolism and nutrition disorders
Dehydration
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
3.3%
2/61 • Number of events 2 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Infections and infestations
Fungal infection
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Infections and infestations
Infected skin ulcer
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Infections and infestations
Pneumonia
|
1.5%
1/65 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Infections and infestations
Wound infection
|
0.00%
0/65 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
Other adverse events
| Measure |
Cebranopadol
n=65 participants at risk
Once daily oral administration. 200, 400 or 600 µg film coated tablets. Dosage 200 µg to 1000 µg per day.
Cebranopadol: Participant will take one or two tablet(s) of cebranopadol in the morning and one or two placebo double-dummy morphine-like capsule(s) in the morning and the evening.
|
Morphine Prolonged Release
n=61 participants at risk
Twice daily oral administration. 15, 30 or 45 mg morphine sulfate capsules. Dosage 30 to 150 mg per day.
Morphine Prolonged Release: Participant will take one or two morphine capsule(s) in the morning and in the evening and one or two placebo double-dummy cebranopadol-like tablet(s) in the morning.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
4.6%
3/65 • Number of events 3 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
8.2%
5/61 • Number of events 5 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Nervous system disorders
Somnolence
|
9.2%
6/65 • Number of events 7 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
8.2%
5/61 • Number of events 5 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Nervous system disorders
Paraesthesia
|
6.2%
4/65 • Number of events 4 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Nervous system disorders
Dizziness
|
3.1%
2/65 • Number of events 2 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
9.8%
6/61 • Number of events 6 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Ear and labyrinth disorders
Vertigo
|
3.1%
2/65 • Number of events 2 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
6.6%
4/61 • Number of events 4 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
General disorders
Fatigue
|
10.8%
7/65 • Number of events 7 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
16.4%
10/61 • Number of events 10 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
General disorders
Oedema peripheral
|
10.8%
7/65 • Number of events 8 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
0.00%
0/61 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
General disorders
Asthenia
|
9.2%
6/65 • Number of events 6 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
13.1%
8/61 • Number of events 9 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
General disorders
Pyrexia
|
6.2%
4/65 • Number of events 6 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
6.6%
4/61 • Number of events 5 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Psychiatric disorders
Anxiety
|
6.2%
4/65 • Number of events 4 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
1.6%
1/61 • Number of events 1 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Gastrointestinal disorders
Constipation
|
12.3%
8/65 • Number of events 11 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
24.6%
15/61 • Number of events 15 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Gastrointestinal disorders
Nausea
|
12.3%
8/65 • Number of events 11 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
16.4%
10/61 • Number of events 12 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Gastrointestinal disorders
Vomiting
|
12.3%
8/65 • Number of events 13 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
8.2%
5/61 • Number of events 6 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
4/65 • Number of events 4 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
8.2%
5/61 • Number of events 8 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Metabolism and nutrition disorders
Decreased appetite
|
7.7%
5/65 • Number of events 5 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
14.8%
9/61 • Number of events 10 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
|
Infections and infestations
Urinary tract infection
|
3.1%
2/65 • Number of events 2 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
9.8%
6/61 • Number of events 6 • From first IMP intake up to day of last IMP in Week 6 + 3 weeks follow-up (max. 9 weeks in total). The All-Cause Mortality is reported for the Allocated Set. Serious and non-serious treatment emergent adverse events (i.e. events documented after the first dose of study medication and events which started before treatment and worsened after first dose of study medication) are reported for the Safety Set (all participants with at least one dose of study medication).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.
- Publication restrictions are in place
Restriction type: OTHER