Trial Outcomes & Findings for Cebranopadol Efficacy and Safety in Diabetic Patients Suffering From Chronic Pain Caused by Damage to the Nerves (NCT NCT01939366)
NCT ID: NCT01939366
Last Updated: 2021-07-15
Results Overview
Participants will be asked to record their pain intensity in the evening. Participants are asked to rate how much pain they had on average in the past 24 hours. The participant scores 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". Baseline average pain scores are calculated from the averages of all scores recorded during the 3 days prior to randomization. The average pain at week 6 will be the average pain scores calculated from all pain scores measured during week 6.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
699 participants
Primary outcome timeframe
Baseline; to End of Week 6 of the Maintenance Phase
Results posted on
2021-07-15
Participant Flow
The trial started on 27 Sep 2013 with the enrollment of the first participants and was completed on 28 Jan 2015 when the last participant completed the last follow-up examination according to the protocol.
Of the 699 participants enrolled 370 participants were not allocated (322 did not meet the eligibility criteria, 29 withdrew consent, 6 due to Adverse Events, 2 due to protocol deviations, 11 due to other reasons). 13 participants allocated to treatment were excluded from the PPS, FAS \& SAF analyses populations due to GCP non-compliance at 2 sites.
Participant milestones
| Measure |
Cebranopadol 100 µg
Cebranopadol 100 µg: Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.
|
Cebranopadol 300 µg
Cebranopadol 300 µg: Participants randomized to 300 μg cebranopadol will start with 100 μg per day and increase to 300 µg per day on day 4 and will remain on 300 µg per day.
|
Cebranopadol 600 µg
Cebranopadol 600 µg: Participants randomized to 600 μg cebranopadol will start with 200 μg per day and increase to 400 µg per day on day 4 and to 600 µg on day 7, thereafter they will remain on 600 µg per day.
|
Pregabalin
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
|
Matching Placebo
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
66
|
64
|
65
|
68
|
66
|
|
Overall Study
Allocated Set Excl. Non-compliant Sites
|
64
|
61
|
63
|
65
|
63
|
|
Overall Study
Safety Set
|
64
|
61
|
62
|
65
|
62
|
|
Overall Study
Full Analysis Set
|
64
|
60
|
61
|
65
|
62
|
|
Overall Study
Per Protocol Set
|
58
|
55
|
50
|
51
|
49
|
|
Overall Study
COMPLETED
|
52
|
41
|
27
|
51
|
48
|
|
Overall Study
NOT COMPLETED
|
14
|
23
|
38
|
17
|
18
|
Reasons for withdrawal
| Measure |
Cebranopadol 100 µg
Cebranopadol 100 µg: Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.
|
Cebranopadol 300 µg
Cebranopadol 300 µg: Participants randomized to 300 μg cebranopadol will start with 100 μg per day and increase to 300 µg per day on day 4 and will remain on 300 µg per day.
|
Cebranopadol 600 µg
Cebranopadol 600 µg: Participants randomized to 600 μg cebranopadol will start with 200 μg per day and increase to 400 µg per day on day 4 and to 600 µg on day 7, thereafter they will remain on 600 µg per day.
|
Pregabalin
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
|
Matching Placebo
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
8
|
17
|
30
|
8
|
5
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
1
|
1
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
0
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
2
|
2
|
3
|
|
Overall Study
Inclusion criteria not met
|
0
|
1
|
1
|
0
|
1
|
|
Overall Study
Other
|
0
|
0
|
2
|
2
|
1
|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Sponsor decision
|
0
|
0
|
0
|
0
|
2
|
|
Overall Study
GCP non-compliance at site
|
2
|
3
|
2
|
3
|
3
|
Baseline Characteristics
Cebranopadol Efficacy and Safety in Diabetic Patients Suffering From Chronic Pain Caused by Damage to the Nerves
Baseline characteristics by cohort
| Measure |
Cebranopadol 100 µg
n=64 Participants
Cebranopadol 100 µg: Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.
|
Cebranopadol 300 µg
n=61 Participants
Cebranopadol 300 µg: Participants randomized to 300 μg cebranopadol will start with 100 μg per day and increase to 300 µg per day on day 4 and will remain on 300 µg per day.
|
Cebranopadol 600 µg
n=62 Participants
Cebranopadol 600 µg: Participants randomized to 600 μg cebranopadol will start with 200 μg per day and increase to 400 µg per day on day 4 and to 600 µg on day 7, thereafter they will remain on 600 µg per day.
|
Pregabalin
n=65 Participants
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
|
Matching Placebo
n=62 Participants
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
|
Total
n=314 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
62.2 years
STANDARD_DEVIATION 8.6 • n=5 Participants
|
61.6 years
STANDARD_DEVIATION 8.7 • n=7 Participants
|
62.2 years
STANDARD_DEVIATION 8.1 • n=5 Participants
|
61.7 years
STANDARD_DEVIATION 9.9 • n=4 Participants
|
63.3 years
STANDARD_DEVIATION 10.3 • n=21 Participants
|
62.2 years
STANDARD_DEVIATION 9.1 • n=8 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
94 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
49 Participants
n=21 Participants
|
220 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
34 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
57 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
55 Participants
n=4 Participants
|
57 Participants
n=21 Participants
|
280 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
4 Participants
n=8 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
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
61 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
61 Participants
n=21 Participants
|
295 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
|
Region of Enrollment
Austria
|
5 participants
n=5 Participants
|
6 participants
n=7 Participants
|
5 participants
n=5 Participants
|
6 participants
n=4 Participants
|
5 participants
n=21 Participants
|
27 participants
n=8 Participants
|
|
Region of Enrollment
Netherlands
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
4 participants
n=5 Participants
|
2 participants
n=4 Participants
|
4 participants
n=21 Participants
|
16 participants
n=8 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
10 participants
n=7 Participants
|
9 participants
n=5 Participants
|
13 participants
n=4 Participants
|
10 participants
n=21 Participants
|
55 participants
n=8 Participants
|
|
Region of Enrollment
Denmark
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
2 participants
n=21 Participants
|
9 participants
n=8 Participants
|
|
Region of Enrollment
Italy
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
2 participants
n=4 Participants
|
1 participants
n=21 Participants
|
9 participants
n=8 Participants
|
|
Region of Enrollment
France
|
7 participants
n=5 Participants
|
7 participants
n=7 Participants
|
8 participants
n=5 Participants
|
8 participants
n=4 Participants
|
8 participants
n=21 Participants
|
38 participants
n=8 Participants
|
|
Region of Enrollment
Germany
|
31 participants
n=5 Participants
|
30 participants
n=7 Participants
|
30 participants
n=5 Participants
|
32 participants
n=4 Participants
|
31 participants
n=21 Participants
|
154 participants
n=8 Participants
|
|
Region of Enrollment
Spain
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
2 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
6 participants
n=8 Participants
|
|
Height
|
1.721 meter
STANDARD_DEVIATION 0.098 • n=5 Participants
|
1.736 meter
STANDARD_DEVIATION 0.092 • n=7 Participants
|
1.717 meter
STANDARD_DEVIATION 0.104 • n=5 Participants
|
1.736 meter
STANDARD_DEVIATION 0.110 • n=4 Participants
|
1.736 meter
STANDARD_DEVIATION 0.076 • n=21 Participants
|
1.729 meter
STANDARD_DEVIATION 0.097 • n=8 Participants
|
|
Weight
|
95.77 kilogram
STANDARD_DEVIATION 15.62 • n=5 Participants
|
96.51 kilogram
STANDARD_DEVIATION 18.12 • n=7 Participants
|
93.72 kilogram
STANDARD_DEVIATION 16.05 • n=5 Participants
|
92.25 kilogram
STANDARD_DEVIATION 17.28 • n=4 Participants
|
99.00 kilogram
STANDARD_DEVIATION 15.99 • n=21 Participants
|
95.42 kilogram
STANDARD_DEVIATION 16.69 • n=8 Participants
|
|
BMI
|
32.30 kilogram per square meter
STANDARD_DEVIATION 4.41 • n=5 Participants
|
31.87 kilogram per square meter
STANDARD_DEVIATION 4.39 • n=7 Participants
|
31.70 kilogram per square meter
STANDARD_DEVIATION 4.29 • n=5 Participants
|
30.66 kilogram per square meter
STANDARD_DEVIATION 5.26 • n=4 Participants
|
32.80 kilogram per square meter
STANDARD_DEVIATION 4.53 • n=21 Participants
|
31.86 kilogram per square meter
STANDARD_DEVIATION 4.62 • n=8 Participants
|
|
Pain Assessment - Average 24-hour pain
|
6.92 units on a scale
STANDARD_DEVIATION 1.34 • n=5 Participants
|
6.80 units on a scale
STANDARD_DEVIATION 1.37 • n=7 Participants
|
6.80 units on a scale
STANDARD_DEVIATION 1.25 • n=5 Participants
|
6.78 units on a scale
STANDARD_DEVIATION 1.22 • n=4 Participants
|
6.84 units on a scale
STANDARD_DEVIATION 1.15 • n=21 Participants
|
6.83 units on a scale
STANDARD_DEVIATION 1.26 • n=8 Participants
|
|
Pain Assessment - Worst 24-hour pain
|
7.41 units on a scale
STANDARD_DEVIATION 1.36 • n=5 Participants
|
7.32 units on a scale
STANDARD_DEVIATION 1.28 • n=7 Participants
|
7.38 units on a scale
STANDARD_DEVIATION 1.21 • n=5 Participants
|
7.32 units on a scale
STANDARD_DEVIATION 1.16 • n=4 Participants
|
7.33 units on a scale
STANDARD_DEVIATION 1.14 • n=21 Participants
|
7.35 units on a scale
STANDARD_DEVIATION 1.23 • n=8 Participants
|
|
Pain Assessment - Current Morning Pain
|
6.60 units on a scale
STANDARD_DEVIATION 1.58 • n=5 Participants
|
6.58 units on a scale
STANDARD_DEVIATION 1.53 • n=7 Participants
|
6.44 units on a scale
STANDARD_DEVIATION 1.46 • n=5 Participants
|
6.61 units on a scale
STANDARD_DEVIATION 1.44 • n=4 Participants
|
6.58 units on a scale
STANDARD_DEVIATION 1.48 • n=21 Participants
|
6.56 units on a scale
STANDARD_DEVIATION 1.49 • n=8 Participants
|
|
Pain Assessment - Current Evening Pain
|
6.98 units on a scale
STANDARD_DEVIATION 1.50 • n=5 Participants
|
6.87 units on a scale
STANDARD_DEVIATION 1.46 • n=7 Participants
|
6.68 units on a scale
STANDARD_DEVIATION 1.33 • n=5 Participants
|
6.75 units on a scale
STANDARD_DEVIATION 1.36 • n=4 Participants
|
6.55 units on a scale
STANDARD_DEVIATION 1.34 • n=21 Participants
|
6.80 units on a scale
STANDARD_DEVIATION 1.40 • n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline; to End of Week 6 of the Maintenance PhasePopulation: Full Analysis Set (FAS). Mixed-effects model for repeated measures (MMRM).
Participants will be asked to record their pain intensity in the evening. Participants are asked to rate how much pain they had on average in the past 24 hours. The participant scores 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". Baseline average pain scores are calculated from the averages of all scores recorded during the 3 days prior to randomization. The average pain at week 6 will be the average pain scores calculated from all pain scores measured during week 6.
Outcome measures
| Measure |
Cebranopadol 100 µg
n=64 Participants
Cebranopadol 100 µg: Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.
|
Cebranopadol 300 µg
n=60 Participants
Cebranopadol 300 µg: Participants randomized to 300 μg cebranopadol will start with 100 μg per day and increase to 300 µg per day on day 4 and will remain on 300 µg per day.
|
Cebranopadol 600 µg
n=58 Participants
Cebranopadol 600 µg: Participants randomized to 600 μg cebranopadol will start with 200 μg per day and increase to 400 µg per day on day 4 and to 600 µg on day 7, thereafter they will remain on 600 µg per day.
|
Pregabalin
n=64 Participants
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
|
Matching Placebo
n=61 Participants
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
|
|---|---|---|---|---|---|
|
Change in Average Pain Intensity.
|
-2.24 units on a scale
Interval -2.78 to -1.7
|
-2.28 units on a scale
Interval -2.86 to -1.71
|
-2.56 units on a scale
Interval -3.2 to -1.91
|
-2.79 units on a scale
Interval -3.33 to -2.26
|
-1.55 units on a scale
Interval -2.1 to -1.0
|
Adverse Events
Cebranopadol 100 µg
Serious events: 1 serious events
Other events: 47 other events
Deaths: 0 deaths
Cebranopadol 300 µg
Serious events: 2 serious events
Other events: 50 other events
Deaths: 0 deaths
Cebranopadol 600 µg
Serious events: 4 serious events
Other events: 53 other events
Deaths: 0 deaths
Pregabalin
Serious events: 1 serious events
Other events: 49 other events
Deaths: 0 deaths
Matching Placebo
Serious events: 2 serious events
Other events: 43 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Cebranopadol 100 µg
n=64 participants at risk
Cebranopadol 100 µg: Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.
|
Cebranopadol 300 µg
n=61 participants at risk
Cebranopadol 300 µg: Participants randomized to 300 μg cebranopadol will start with 100 μg per day and increase to 300 µg per day on day 4 and will remain on 300 µg per day.
|
Cebranopadol 600 µg
n=62 participants at risk
Cebranopadol 600 µg: Participants randomized to 600 μg cebranopadol will start with 200 μg per day and increase to 400 µg per day on day 4 and to 600 µg on day 7, thereafter they will remain on 600 µg per day.
|
Pregabalin
n=65 participants at risk
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
|
Matching Placebo
n=62 participants at risk
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Gastrointestinal disorders
Diverticulum Intestinal Haemorrhagic
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.5%
1/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.2%
2/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
General disorders
Peripheral Swelling
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Metabolism and nutrition disorders
Diabetes Mellitus
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Nervous system disorders
Hypoglycaemic Coma
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Renal and urinary disorders
Renal Failure Acute
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Vascular disorders
Haematoma
|
1.6%
1/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
Other adverse events
| Measure |
Cebranopadol 100 µg
n=64 participants at risk
Cebranopadol 100 µg: Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.
|
Cebranopadol 300 µg
n=61 participants at risk
Cebranopadol 300 µg: Participants randomized to 300 μg cebranopadol will start with 100 μg per day and increase to 300 µg per day on day 4 and will remain on 300 µg per day.
|
Cebranopadol 600 µg
n=62 participants at risk
Cebranopadol 600 µg: Participants randomized to 600 μg cebranopadol will start with 200 μg per day and increase to 400 µg per day on day 4 and to 600 µg on day 7, thereafter they will remain on 600 µg per day.
|
Pregabalin
n=65 participants at risk
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
|
Matching Placebo
n=62 participants at risk
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.8%
6/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.2%
2/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Gastrointestinal disorders
Constipation
|
4.7%
3/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.8%
6/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
11.3%
7/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.2%
6/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.2%
2/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
4/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.3%
2/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
4.8%
3/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.1%
2/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
8.1%
5/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Gastrointestinal disorders
Dry mouth
|
1.6%
1/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
12.9%
8/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.5%
1/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Gastrointestinal disorders
Nausea
|
9.4%
6/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
36.1%
22/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
25.8%
16/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.2%
6/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.7%
6/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Gastrointestinal disorders
Vomiting
|
3.1%
2/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
16.4%
10/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
27.4%
17/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.5%
1/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.2%
2/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
General disorders
Fatigue
|
12.5%
8/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
18.0%
11/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
16.1%
10/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
7.7%
5/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.2%
2/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
General disorders
Oedema peripheral
|
4.7%
3/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
4.9%
3/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.2%
6/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Infections and infestations
Bacteriuria
|
7.8%
5/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
4.9%
3/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
4.8%
3/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.2%
6/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.7%
6/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Infections and infestations
Nasopharyngitis
|
4.7%
3/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
7.7%
5/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.7%
6/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Investigations
Weight increased
|
0.00%
0/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
7.7%
5/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Nervous system disorders
Dizziness
|
12.5%
8/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
16.4%
10/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
33.9%
21/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
18.5%
12/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.7%
6/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Nervous system disorders
Headache
|
4.7%
3/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.8%
6/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
4.8%
3/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
6.2%
4/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.2%
2/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Nervous system disorders
Somnolence
|
4.7%
3/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
13.1%
8/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
12.9%
8/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
4.6%
3/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Nervous system disorders
Tremor
|
1.6%
1/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
6.2%
4/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Psychiatric disorders
Depressed mood
|
1.6%
1/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.6%
1/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.2%
2/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
0.00%
0/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
6.5%
4/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
4.7%
3/64 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
13.1%
8/61 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
9.7%
6/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
1.5%
1/65 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
3.2%
2/62 • Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The sponsor reserves the right to review any proposed presentation of the results of this trial before they are submitted for publication or public disclosure. Neither party has the right to prohibit publication or public disclosure unless it can be shown to affect possible patent rights.
- Publication restrictions are in place
Restriction type: OTHER