Cebranopadol Efficacy and Safety in Diabetic Patients Suf... | NCT01939366 | Trialant
NCT01939366
Sponsor
Tris Pharma, Inc.
Status
Completed
Last Update Posted
Jul 15, 2021Actual
Enrollment
699Actual
Phase
Phase 2
Conditions
Chronic Pain
Diabetic Neuropathies
Diabetes Mellitus
Interventions
Cebranopadol 100 µg
Cebranopadol 300 µg
Cebranopadol 600 µg
Pregabalin
Matching Placebo
Countries
United States
Austria
Denmark
France
Germany
Italy
Netherlands
Spain
Protocol Section
Identification Module
NCT ID
NCT01939366
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
KF6005/08
Secondary IDs
ID
Type
Description
Link
2013-000473-68
EudraCT Number
U1111-1151-4331
Other Identifier
WHO UTN
Brief Title
Cebranopadol Efficacy and Safety in Diabetic Patients Suffering From Chronic Pain Caused by Damage to the Nerves
Official Title
Efficacy, Safety and Tolerability of Multiple Doses of Oral Cebranopadol in Subjects With Moderate to Severe Chronic Pain Due to Diabetic Peripheral Neuropathy.
Acronym
Not provided
Organization
Tris Pharma, Inc.INDUSTRY
Status Module
Record Verification Date
Jul 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 27, 2013Actual
Primary Completion Date
Jan 2015Actual
Completion Date
Jan 28, 2015Actual
First Submitted Date
Sep 6, 2013
First Submission Date that Met QC Criteria
Sep 6, 2013
First Posted Date
Sep 11, 2013Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 22, 2015
Results First Submitted that Met QC Criteria
Dec 11, 2019
Results First Posted Date
Dec 26, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jul 13, 2021
Last Update Posted Date
Jul 15, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Tris Pharma, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this trial is to evaluate if cebranopadol is safe and can decrease pain in patients when compared to placebo (a tablet that does not contain active product) and when compared to a marketed product containing pregabalin (Lyrica®). Furthermore, this trial will be undertaken to find out if the patient's general health and well-being improves under trial treatment.
The concentrations of cebranopadol in the blood will be investigated to get a better understanding of how it is absorbed from the gut, distributed and broken down in the body, and eliminated from the body.
Detailed Description
Not provided
Conditions Module
Conditions
Chronic Pain
Diabetic Neuropathies
Diabetes Mellitus
Keywords
Painful Diabetic Peripheral Neuropathy
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
699Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cebranopadol 300 µg
Experimental
Drug: Cebranopadol 300 µg
Cebranopadol 600 µg
Experimental
Drug: Cebranopadol 600 µg
Pregabalin
Active Comparator
Drug: Pregabalin
Matching Placebo
Placebo Comparator
Drug: Matching Placebo
Cebranopadol 100 µg
Experimental
Drug: Cebranopadol 100 µg
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Cebranopadol 100 µg
Drug
Participants randomized to 100 μg cebranopadol will start with 100 μg per day and will remain on 100 µg per day.
Cebranopadol 100 µg
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Change in Average Pain Intensity.
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.
Baseline; to End of Week 6 of the Maintenance Phase
Secondary Outcomes
Not provided
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
written signed informed consent
type 1 or type 2 diabetes mellitus
clinical diagnosis of painful Diabetic Polyneuropathic Neuropathy (DPN) with symptoms and signs for at least 3 months
must require medication (e.g., non-opioids or opioids up to an equivalent dose of 160 mg oral morphine/day) for the treatment of pain due to DPN for at least 1 month prior to Visit 1 and must be dissatisfied with the current treatment (in terms of efficacy and/or tolerability). Medication for the treatment of pain due to DPN should be required on at least 4 of 7 consecutive days.
blood glucose to be controlled by a diet, oral anti-hyperglycemic medication, and/or insulin for at least 3 months prior. Glycosylated hemoglobin (HbA1C) should not be greater than 11%
baseline pain intensity score greater or equal to 5 on the 11-point Numerical Rating Scale (NRS) without intake of any analgesic at allocation. For each of the last 3 days prior to allocation of treatment, a 24 hour NRS score greater or equal to 4 is required
women of childbearing potential must have a negative urine pregnancy test at enrollment
using medically acceptable and highly effective methods of birth control (and willing to use them during the trial).
Exclusion Criteria:
presence of other pain that could confound the painful Diabetic Polyneuropathy (DPN) assessments, e.g. pain due to nerve entrapment (tarsal tunnel syndrome, osteoarthritis of the knee etc), peripheral vascular disease, radiculopathy, plantar fasciitis, tendonitis, mononeuritis multiplex, postherpetic neuralgia, complex regional pain syndrome, or fibromyalgia.
neuropathy due to etiologies other than diabetes, e.g. autoimmune disorders, inflammatory neuropathies (e.g. chronic inflammatory demyelinating polyneuropathy), thyroid disease or endocrine disorders (other than diabetes), heavy metal or toxic neuropathy, nutritional deficiency, metabolic disorders, vasculitis, infections, injury, or paraneoplastic syndromes.
severe or extensive diabetic ulcers or amputations due to diabetes
Charcot's joints due to diabetes.
any clinically significant disease or laboratory findings, e.g., significant unstable cardiac, vascular, pulmonary, gastrointestinal, endocrine, metabolic, neurological, or psychiatric disorders.
inability to comply with the protocol and with the intake of trial medication that, in the investigator's opinion, might indicate that the participant is unsuitable for the trial.
conditions that require treatment with medication that is not allowed to be taken during the trial
previous or current alcohol or drug abuse or opioid dependency.
severe functional hepatic impairment corresponding to Child-Pugh classification C.
history of acute hepatitis
impaired renal function, a creatinine clearance less than 60 mL/min at the enrollment (Cockcroft-Gault calculated).
history of any major gastrointestinal procedures (e.g., gastric bypass) or gastrointestinal conditions (e.g. acute diarrhea, blind loop syndrome, gastric dumping syndrome, Whipple's disease) that might affect the absorption or metabolism of cebranopadol or pregabalin.
risk factors for or history of torsade de pointes and/or marked prolongation of the QT interval (e.g. heart failure, hypokalemia, or bradycardia).
history of seizure disorder and/or epilepsy or any condition associated with a significant risk for seizure disorder or epilepsy at the discretion of the investigator.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
80 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Director Clinical Trials
Grünenthal GmbH
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
US002
Mesa
Arizona
85215
United States
US001
References Module
No data available
No data is available for this block.
IPD Sharing Statement Module
Plan to Share IPD
No
Description
Not provided
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
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.
Recruitment Details
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.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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.
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 300 µg
Cebranopadol 600 µg
Drug
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.
Cebranopadol 600 µg
Pregabalin
Drug
Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
Pregabalin
Lyrica®
Matching Placebo
Drug
Placebo will be matched to pregabalin and cebranopadol.
Matching Placebo
Garden Grove
California
92843
United States
US019
Laguna Hills
California
92653
United States
US014
National City
California
91950
United States
US007
Orange
California
92868
United States
US011
Hialeah
Florida
33012
United States
US012
Miami
Florida
33135
United States
US009
Orlando
Florida
32806
United States
US004
Blackfoot
Idaho
83221
United States
US006
Elgin
Illinois
60123
United States
US016
West Long Branch
New Jersey
07764
United States
US008
Brooklyn
New York
11229
United States
US005
Brooklyn
New York
11235
United States
US021
New York
New York
10128
United States
US003
West Jordan
Utah
84088
United States
AT007
Graz
8036
Austria
AT005
Salzburg
5020
Austria
AT004
Senftenberg
3541
Austria
AT002
Vienna
1010
Austria
AT003
Vienna
1060
Austria
AT001
Vienna
1090
Austria
AT006
Vienna
1160
Austria
DK005
Aalborg
9100
Denmark
DK003
Aarhus
8000
Denmark
DK002
Copenhagen
2000
Denmark
DK001
Odense
5000
Denmark
FR008
Corbeil-Essonnes
91100
France
FR001
Lille
59037
France
FR007
Limoges
87042
France
FR005
Montauban
82013
France
FR002
Nantes
44200
France
FR004
Orléans
45000
France
FR006
Paris
75004
France
DE018
Aschaffenburg
63739
Germany
DE003
Bad Oeynhausen
32545
Germany
DE005
Berlin
10115
Germany
DE023
Berlin
10117
Germany
DE031
Berlin
10787
Germany
DE004
Berlin
12627
Germany
DE025
Berlin
13125
Germany
DE013
Bochum
44787
Germany
DE033
Dresden
01069
Germany
DE017
Düsseldorf
40210
Germany
DE012
Düsseldorf
40212
Germany
DE010
Essen
45136
Germany
DE034
Essen
45277
Germany
DE022
Essen
45355
Germany
DE006
Frankfurt
60596
Germany
DE007
Görlitz
02826
Germany
DE021
Hamburg
20253
Germany
DE020
Hanover
30159
Germany
DE016
Karlsruhe
76199
Germany
DE002
Kiel
24119
Germany
DE030
Künzing
94550
Germany
DE008
Leipzig
04103
Germany
DE009
Leipzig
04109
Germany
DE015
Magdeburg
39104
Germany
DE032
Magdeburg
39112
Germany
DE001
Mainz
55116
Germany
DE028
Mayen
56727
Germany
DE027
München
81477
Germany
DE014
Münster
48145
Germany
DE011
Neuss
41460
Germany
DE024
Schwerin
19055
Germany
IT005
Ancona
60127
Italy
IT004
Milan
20162
Italy
IT001
Rome
00133
Italy
IT002
Turin
10126
Italy
NL007
Amsterdam
1091 AC
Netherlands
NL004
Apeldoorn
7334 DZ
Netherlands
NL005
Beek
6191 JW
Netherlands
NL001
Eindhoven
5623 EJ
Netherlands
NL002
Rotterdam
3039 BD
Netherlands
NL006
Venlo
5912 BL
Netherlands
NL008
Zwijndrecht
3331 LZ
Netherlands
NL003
Zwolle
8025 AB
Netherlands
ES001
Cuenca
16002
Spain
ES011
Madrid
28031
Spain
ES010
Madrid
28040
Spain
ES009
Madrid
28041
Spain
ES003
Toledo
45600
Spain
ES006
Valencia
46010
Spain
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.
FG002
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.
FG003
Pregabalin
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
FG004
Matching Placebo
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
FG00066 subjects
FG00164 subjects
FG00265 subjects
FG00368 subjects
FG00466 subjects
Allocated Set Excl. Non-compliant Sites
FG00064 subjects
FG00161 subjects
FG00263 subjects
FG00365 subjects
FG00463 subjects
Safety Set
FG00064 subjects
FG00161 subjects
FG00262 subjects
FG00365 subjects
FG00462 subjects
Full Analysis Set
FG00064 subjects
FG00160 subjects
FG00261 subjects
FG00365 subjects
FG00462 subjects
Per Protocol Set
FG00058 subjects
FG00155 subjects
FG00250 subjects
FG00351 subjects
FG00449 subjects
COMPLETED
FG00052 subjects
FG00141 subjects
FG00227 subjects
FG00351 subjects
FG00448 subjects
NOT COMPLETED
FG00014 subjects
FG00123 subjects
FG00238 subjects
FG00317 subjects
FG00418 subjects
Type
Comment
Reasons
Adverse Event
FG0008 subjects
FG00117 subjects
FG00230 subjects
FG0038 subjects
FG0045 subjects
Lack of Efficacy
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG0031 subjects
FG004
Lost to Follow-up
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG0022 subjects
FG0032 subjects
FG004
Inclusion criteria not met
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Other
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0032 subjects
FG004
Protocol Violation
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Sponsor decision
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
GCP non-compliance at site
FG0002 subjects
FG0013 subjects
FG0022 subjects
FG0033 subjects
FG004
Full Analysis Set
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
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.
BG001
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.
BG002
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.
BG003
Pregabalin
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
BG004
Matching Placebo
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00064
BG00161
BG00262
BG00365
BG00462
BG005314
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00062.2± 8.6
BG00161.6± 8.7
BG00262.2± 8.1
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00020
BG00123
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0007
BG0016
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Austria
Title
Measurements
BG0005
BG0016
BG002
Height
Mean
Standard Deviation
meter
Title
Denominators
Categories
Title
Measurements
BG0001.721± 0.098
BG0011.736± 0.092
BG002
Weight
Mean
Standard Deviation
kilogram
Title
Denominators
Categories
Title
Measurements
BG00095.77± 15.62
BG00196.51± 18.12
BG002
BMI
Mean
Standard Deviation
kilogram per square meter
Title
Denominators
Categories
Title
Measurements
BG00032.30± 4.41
BG00131.87± 4.39
BG002
Pain Assessment - Average 24-hour pain
Participants recorded their current pain twice daily (morning and evening), and, with a recall period of 24 hours, their worst and 24-hour pain once daily in the evening. Pain was assessed using an 11-point numerical rating scale (NRS). Participants had to select a number corresponding to their pain, with anchors at 0 for "no pain" and 10 for "pain as bad as you can imagine". The average baseline pain was calculated as the average over the three 24-hour pain assessments of the last 3 days prior to the Baseline Visit.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0006.92± 1.34
BG001
Pain Assessment - Worst 24-hour pain
Participants recorded their current pain twice daily (morning and evening), and, with a recall period of 24 hours, their worst and 24-hour pain once daily in the evening. Pain was assessed using an 11-point numerical rating scale (NRS). Participants had to select a number corresponding to their pain, with anchors at 0 for "no pain" and 10 for "pain as bad as you can imagine". The worst 24-hour pain was calculated as the average over the three 24-hour pain assessments of the last 3 days prior to the Baseline Visit.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0007.41± 1.36
BG001
Pain Assessment - Current Morning Pain
Participants recorded their current pain twice daily (morning and evening), and, with a recall period of 24 hours, their worst and 24-hour pain once daily in the evening. Pain was assessed using an 11-point numerical rating scale (NRS). Participants had to select a number corresponding to their pain, with anchors at 0 for "no pain" and 10 for "pain as bad as you can imagine". The current morning pain at baseline was calculated as the average over the three pain assessments of the last 3 days prior to the Baseline Visit.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0006.60± 1.58
BG001
Pain Assessment - Current Evening Pain
Participants recorded their current pain twice daily (morning and evening), and, with a recall period of 24 hours, their worst and 24-hour pain once daily in the evening. Pain was assessed using an 11-point numerical rating scale (NRS). Participants had to select a number corresponding to their pain, with anchors at 0 for "no pain" and 10 for "pain as bad as you can imagine". The current evening pain at baseline was calculated as the average over the three pain assessments of the last 3 days prior to the Baseline Visit.
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
Title
Measurements
BG0006.98± 1.50
BG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Change in Average Pain Intensity.
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.
Full Analysis Set (FAS). Mixed-effects model for repeated measures (MMRM).
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline; to End of Week 6 of the Maintenance Phase
ID
Title
Description
OG000
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.
OG001
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.
OG002
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.
OG003
Pregabalin
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
OG004
Matching Placebo
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
Units
Counts
Participants
OG00064
OG00160
OG00258
OG003
Title
Denominators
Categories
Title
Measurements
OG000-2.24(-2.78 to -1.70)
OG001-2.28(-2.86 to -1.71)
OG002-2.56(-3.20 to -1.91)
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG004
The mixed model repeated measurement (MMRM) model included fixed effects of pooled sites, treatment, week, treatment-by-week interaction, baseline pain, and a subject-specific random effect. The model was based on the weekly average 24-hour pain intensity of the 2 weeks in the Titration Phase and 6 weeks in the Maintenance Phase. An unstructured covariance matrix was used to model the covariance structure, denominator degrees of freedom were estimated using the Kenward-Roger approximation.
Mixed Models Analysis
The analysis consisted of the contrasts (mixed model Wald tests) of individual cebranopadol doses versus placebo during Week 6 of Maintenance Phase.
0.0621
Due to the exploratory character of this trial, no multiple testing adjustment for control of the false positive rate was applied.
Mean Difference (Final Values)
-0.70
Standard Error of the Mean
0.37
2-Sided
95
-1.43
0.04
Time Frame
Safety Analysis Set Baseline Visit (Day 1) to End of Maintenance Phase (Day 57).
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
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.
0
64
1
64
47
64
EG001
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.
0
61
2
61
50
61
EG002
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.
0
62
4
62
53
62
EG003
Pregabalin
Pregabalin: Stepwise titration from 75 mg twice a day to 300 mg twice a day over 2 weeks.
0
65
1
65
49
65
EG004
Matching Placebo
Matching Placebo: Placebo will be matched to pregabalin and cebranopadol.
0
62
2
62
43
62
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal Pain
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0010 affected61 at risk
EG0021 affected62 at risk
EG0030 affected65 at risk
EG0041 affected62 at risk
Diverticulum Intestinal Haemorrhagic
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0010 affected61 at risk
EG0020 affected62 at risk
EG003
Gastrooesophageal Reflux Disease
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0010 affected61 at risk
EG0021 affected62 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0010 affected61 at risk
EG0022 affected62 at risk
EG003
Peripheral Swelling
General disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0010 affected61 at risk
EG0020 affected62 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0010 affected61 at risk
EG0021 affected62 at risk
EG003
Diabetes Mellitus
Metabolism and nutrition disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0011 affected61 at risk
EG0020 affected62 at risk
EG003
Hypoglycaemic Coma
Nervous system disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0010 affected61 at risk
EG0021 affected62 at risk
EG003
Renal Failure Acute
Renal and urinary disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0011 affected61 at risk
EG0020 affected62 at risk
EG003
Haematoma
Vascular disorders
MedDRA 17.1
Systematic Assessment
EG0001 affected64 at risk
EG0010 affected61 at risk
EG0020 affected62 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abdominal pain upper
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0016 affected61 at risk
EG0020 affected62 at risk
EG0030 affected65 at risk
EG0042 affected62 at risk
Constipation
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0003 affected64 at risk
EG0016 affected61 at risk
EG0027 affected62 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0004 affected64 at risk
EG0012 affected61 at risk
EG0023 affected62 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0001 affected64 at risk
EG0011 affected61 at risk
EG0028 affected62 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0006 affected64 at risk
EG00122 affected61 at risk
EG00216 affected62 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 17.1
Systematic Assessment
EG0002 affected64 at risk
EG00110 affected61 at risk
EG00217 affected62 at risk
EG003
Fatigue
General disorders
MedDRA 17.1
Systematic Assessment
EG0008 affected64 at risk
EG00111 affected61 at risk
EG00210 affected62 at risk
EG003
Oedema peripheral
General disorders
MedDRA 17.1
Systematic Assessment
EG0003 affected64 at risk
EG0013 affected61 at risk
EG0021 affected62 at risk
EG003
Bacteriuria
Infections and infestations
MedDRA 17.1
Systematic Assessment
EG0005 affected64 at risk
EG0013 affected61 at risk
EG0023 affected62 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 17.1
Systematic Assessment
EG0003 affected64 at risk
EG0011 affected61 at risk
EG0021 affected62 at risk
EG003
Weight increased
Investigations
MedDRA 17.1
Systematic Assessment
EG0000 affected64 at risk
EG0010 affected61 at risk
EG0020 affected62 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 17.1
Systematic Assessment
EG0008 affected64 at risk
EG00110 affected61 at risk
EG00221 affected62 at risk
EG003
Headache
Nervous system disorders
MedDRA 17.1
Systematic Assessment
EG0003 affected64 at risk
EG0016 affected61 at risk
EG0023 affected62 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 17.1
Systematic Assessment
EG0003 affected64 at risk
EG0018 affected61 at risk
EG0028 affected62 at risk
EG003
Tremor
Nervous system disorders
MedDRA 17.1
Systematic Assessment
EG0001 affected64 at risk
EG0011 affected61 at risk
EG0021 affected62 at risk
EG003
Depressed mood
Psychiatric disorders
MedDRA 17.1
Systematic Assessment
EG0001 affected64 at risk
EG0011 affected61 at risk
EG0022 affected62 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 17.1
Systematic Assessment
EG0003 affected64 at risk
EG0018 affected61 at risk
EG0026 affected62 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
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.
The mixed model repeated measurement (MMRM) model included fixed effects of pooled sites, treatment, week, treatment-by-week interaction, baseline pain, and a subject-specific random effect. The model was based on the weekly average 24-hour pain intensity of the 2 weeks in the Titration Phase and 6 weeks in the Maintenance Phase. An unstructured covariance matrix was used to model the covariance structure, denominator degrees of freedom were estimated using the Kenward-Roger approximation.
Mixed Models Analysis
The analysis consisted of the contrasts (mixed model Wald tests) of individual cebranopadol doses versus placebo during Week 6 of Maintenance Phase.
0.0564
Due to the exploratory character of this trial, no multiple testing adjustment for control of the false positive rate was applied.
Mean Difference (Final Values)
-0.74
Standard Error of the Mean
0.39
2-Sided
95
-1.50
0.02
Superiority or Other (legacy)
OG002
OG004
The mixed model repeated measurement (MMRM) model included fixed effects of pooled sites, treatment, week, treatment-by-week interaction, baseline pain, and a subject-specific random effect. The model was based on the weekly average 24-hour pain intensity of the 2 weeks in the Titration Phase and 6 weeks in the Maintenance Phase. An unstructured covariance matrix was used to model the covariance structure, denominator degrees of freedom were estimated using the Kenward-Roger approximation.
Mixed Models Analysis
The analysis consisted of the contrasts (mixed model Wald tests) of individual cebranopadol doses versus placebo during Week 6 of Maintenance Phase.
0.0153
Due to the exploratory character of this trial, no multiple testing adjustment for control of the false positive rate was applied.