Trial Outcomes & Findings for A Study in Painful Diabetic Neuropathy (NCT NCT01089556)
NCT ID: NCT01089556
Last Updated: 2013-01-24
Results Overview
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
811 participants
Primary outcome timeframe
Week 8, Week 16
Results posted on
2013-01-24
Participant Flow
The study consisted of 4 study periods (SP): 2 weeks screening and washout (SP I), 8 weeks initial treatment (SP II), 8 weeks intensive treatment (SP III), 2 weeks tapering (SP IV). Participants who did not achieve good pain control during SP II (\<30% improvement) were considered non-responders and continued in the study and entered SP III.
Participant milestones
| Measure |
Duloxetine (SP II)
Duloxetine 30 milligram (mg) daily for Week 1 and 60 mg daily for Weeks 2-8 in Study Period II (SP II).
|
Pregabalin (SP II)
Pregabalin 150 mg daily for Week 1 and 300 mg daily for Weeks 2-8 in Study Period II.
|
Duloxetine (SP III)
Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16 in Study Period III (SP III).
|
DLX + PGB (SP III)
Duloxetine (DLX) 60 mg plus Pregabalin (PGB) 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16 in Study Period III.
|
PGB + DLX (SP III)
Pregabalin (PGB) 300 mg plus Duloxetine (DLX) 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16 in Study Period III.
|
Pregabalin (SP III)
Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16 in Study Period III.
|
|---|---|---|---|---|---|---|
|
Study Period II (Weeks 1-8)
STARTED
|
404
|
407
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Safety Population
|
401
|
403
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Non-responders Who Completed SPII
|
158
|
205
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
COMPLETED
|
333
|
333
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
NOT COMPLETED
|
71
|
74
|
0
|
0
|
0
|
0
|
|
Study Period III (Weeks 9-16)
STARTED
|
0
|
0
|
74
|
75
|
95
|
99
|
|
Study Period III (Weeks 9-16)
Efficacy and Safety Population
|
0
|
0
|
73
|
75
|
94
|
97
|
|
Study Period III (Weeks 9-16)
COMPLETED
|
0
|
0
|
60
|
66
|
83
|
92
|
|
Study Period III (Weeks 9-16)
NOT COMPLETED
|
0
|
0
|
14
|
9
|
12
|
7
|
Reasons for withdrawal
| Measure |
Duloxetine (SP II)
Duloxetine 30 milligram (mg) daily for Week 1 and 60 mg daily for Weeks 2-8 in Study Period II (SP II).
|
Pregabalin (SP II)
Pregabalin 150 mg daily for Week 1 and 300 mg daily for Weeks 2-8 in Study Period II.
|
Duloxetine (SP III)
Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16 in Study Period III (SP III).
|
DLX + PGB (SP III)
Duloxetine (DLX) 60 mg plus Pregabalin (PGB) 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16 in Study Period III.
|
PGB + DLX (SP III)
Pregabalin (PGB) 300 mg plus Duloxetine (DLX) 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16 in Study Period III.
|
Pregabalin (SP III)
Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16 in Study Period III.
|
|---|---|---|---|---|---|---|
|
Study Period II (Weeks 1-8)
Adverse Event
|
35
|
39
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Entry Criteria Not Met
|
12
|
8
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Lack of Efficacy
|
1
|
2
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Lost to Follow-up
|
0
|
3
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Physician Decision
|
4
|
0
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Protocol Violation
|
4
|
4
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Withdrawal by Subject
|
12
|
14
|
0
|
0
|
0
|
0
|
|
Study Period II (Weeks 1-8)
Not received any study drug
|
3
|
4
|
0
|
0
|
0
|
0
|
|
Study Period III (Weeks 9-16)
Adverse Event
|
0
|
0
|
4
|
2
|
4
|
3
|
|
Study Period III (Weeks 9-16)
Entry Criteria Not Met
|
0
|
0
|
1
|
1
|
1
|
1
|
|
Study Period III (Weeks 9-16)
Lack of Efficacy
|
0
|
0
|
0
|
2
|
1
|
0
|
|
Study Period III (Weeks 9-16)
Lost to Follow-up
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Study Period III (Weeks 9-16)
Protocol Violation
|
0
|
0
|
1
|
1
|
1
|
0
|
|
Study Period III (Weeks 9-16)
Satisfactory Response
|
0
|
0
|
4
|
3
|
4
|
1
|
|
Study Period III (Weeks 9-16)
Withdrawal by Subject
|
0
|
0
|
3
|
0
|
1
|
2
|
Baseline Characteristics
A Study in Painful Diabetic Neuropathy
Baseline characteristics by cohort
| Measure |
Duloxetine
n=401 Participants
Duloxetine 30 milligram (mg) daily for Week 1 and 60 mg daily for Weeks 2-8 in Study Period II.
|
Pregabalin
n=403 Participants
Pregabalin 150 mg daily for Week 1 and 300 mg daily for Weeks 2-8 in Study Period II.
|
Total
n=804 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
61.5 years
STANDARD_DEVIATION 10.62 • n=5 Participants
|
61.9 years
STANDARD_DEVIATION 10.95 • n=7 Participants
|
61.7 years
STANDARD_DEVIATION 10.78 • n=5 Participants
|
|
Sex: Female, Male
Female
|
182 Participants
n=5 Participants
|
174 Participants
n=7 Participants
|
356 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
219 Participants
n=5 Participants
|
229 Participants
n=7 Participants
|
448 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
37 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
34 Participants
n=5 Participants
|
34 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
324 Participants
n=5 Participants
|
328 Participants
n=7 Participants
|
652 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
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
Greece
|
16 participants
n=5 Participants
|
12 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
6 participants
n=5 Participants
|
8 participants
n=7 Participants
|
14 participants
n=5 Participants
|
|
Region of Enrollment
Turkey
|
5 participants
n=5 Participants
|
7 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
31 participants
n=5 Participants
|
31 participants
n=7 Participants
|
62 participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
16 participants
n=5 Participants
|
18 participants
n=7 Participants
|
34 participants
n=5 Participants
|
|
Region of Enrollment
France
|
22 participants
n=5 Participants
|
24 participants
n=7 Participants
|
46 participants
n=5 Participants
|
|
Region of Enrollment
Mexico
|
75 participants
n=5 Participants
|
71 participants
n=7 Participants
|
146 participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
19 participants
n=5 Participants
|
19 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
56 participants
n=5 Participants
|
57 participants
n=7 Participants
|
113 participants
n=5 Participants
|
|
Region of Enrollment
Croatia
|
27 participants
n=5 Participants
|
29 participants
n=7 Participants
|
56 participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
27 participants
n=5 Participants
|
22 participants
n=7 Participants
|
49 participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
9 participants
n=5 Participants
|
|
Region of Enrollment
Germany
|
52 participants
n=5 Participants
|
54 participants
n=7 Participants
|
106 participants
n=5 Participants
|
|
Region of Enrollment
Korea, Republic of
|
31 participants
n=5 Participants
|
32 participants
n=7 Participants
|
63 participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
13 participants
n=5 Participants
|
15 participants
n=7 Participants
|
28 participants
n=5 Participants
|
|
Clinical Global Impressions of Severity Scale (CGI-S)
|
4.0 units on a scale
STANDARD_DEVIATION 1.07 • n=5 Participants
|
4.0 units on a scale
STANDARD_DEVIATION 1.09 • n=7 Participants
|
4.0 units on a scale
STANDARD_DEVIATION 1.08 • n=5 Participants
|
|
Patient Global Impressions of Severity Scale (PGI-S)
|
3.4 units on a scale
STANDARD_DEVIATION 1.42 • n=5 Participants
|
3.4 units on a scale
STANDARD_DEVIATION 1.41 • n=7 Participants
|
3.4 units on a scale
STANDARD_DEVIATION 1.42 • n=5 Participants
|
|
Brief Pain Inventory (BPI) Severity: Average Pain Score
|
6.0 units on a scale
STANDARD_DEVIATION 1.55 • n=5 Participants
|
6.0 units on a scale
STANDARD_DEVIATION 1.57 • n=7 Participants
|
6.0 units on a scale
STANDARD_DEVIATION 1.56 • n=5 Participants
|
|
Neuropathic Pain Symptom Inventory (NPSI)
|
47.3 units on a scale
STANDARD_DEVIATION 19.16 • n=5 Participants
|
47.7 units on a scale
STANDARD_DEVIATION 20.46 • n=7 Participants
|
47.5 units on a scale
STANDARD_DEVIATION 19.81 • n=5 Participants
|
|
Hospital Anxiety and Depression Scale (HADS) - Anxiety Subscale Score
|
6.8 units on a scale
STANDARD_DEVIATION 4.31 • n=5 Participants
|
6.6 units on a scale
STANDARD_DEVIATION 4.32 • n=7 Participants
|
6.7 units on a scale
STANDARD_DEVIATION 4.31 • n=5 Participants
|
|
Hospital Anxiety and Depression Scale (HADS) - Depression Subscale Score
|
5.5 units on a scale
STANDARD_DEVIATION 4.19 • n=5 Participants
|
5.5 units on a scale
STANDARD_DEVIATION 3.88 • n=7 Participants
|
5.5 units on a scale
STANDARD_DEVIATION 4.04 • n=5 Participants
|
|
Sheehan Disability Scale (SDS)
|
13.3 units on a scale
STANDARD_DEVIATION 7.47 • n=5 Participants
|
13.3 units on a scale
STANDARD_DEVIATION 7.59 • n=7 Participants
|
13.3 units on a scale
STANDARD_DEVIATION 7.52 • n=5 Participants
|
|
Average number of hours worked for pay per week
|
39.5 hours
STANDARD_DEVIATION 20.33 • n=5 Participants
|
41.4 hours
STANDARD_DEVIATION 16.36 • n=7 Participants
|
40.4 hours
STANDARD_DEVIATION 18.47 • n=5 Participants
|
|
Number of days of work/school missed
|
2.3 days
STANDARD_DEVIATION 7.98 • n=5 Participants
|
1.3 days
STANDARD_DEVIATION 4.69 • n=7 Participants
|
1.8 days
STANDARD_DEVIATION 6.56 • n=5 Participants
|
|
Number of days hospitalized
|
0.0 days
STANDARD_DEVIATION 0.45 • n=5 Participants
|
0.1 days
STANDARD_DEVIATION 0.67 • n=7 Participants
|
0.1 days
STANDARD_DEVIATION 0.57 • n=5 Participants
|
|
Blood pressure (BP)
Systolic BP
|
135.0 millimeter of mercury (mm Hg)
STANDARD_DEVIATION 16.27 • n=5 Participants
|
134.3 millimeter of mercury (mm Hg)
STANDARD_DEVIATION 15.62 • n=7 Participants
|
134.7 millimeter of mercury (mm Hg)
STANDARD_DEVIATION 15.94 • n=5 Participants
|
|
Blood pressure (BP)
Diastolic BP
|
77.6 millimeter of mercury (mm Hg)
STANDARD_DEVIATION 10.04 • n=5 Participants
|
76.7 millimeter of mercury (mm Hg)
STANDARD_DEVIATION 9.43 • n=7 Participants
|
77.1 millimeter of mercury (mm Hg)
STANDARD_DEVIATION 9.74 • n=5 Participants
|
|
Pulse rate
|
76.0 beats per minute (bpm)
STANDARD_DEVIATION 10.81 • n=5 Participants
|
75.6 beats per minute (bpm)
STANDARD_DEVIATION 11.05 • n=7 Participants
|
75.8 beats per minute (bpm)
STANDARD_DEVIATION 10.92 • n=5 Participants
|
PRIMARY outcome
Timeframe: Week 8, Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one BPI measurements during Weeks 9-16 (Study Period III).
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=170 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Change From Week 8 to Week 16 Endpoint in 24 Hour Average Pain Item Score on the Brief Pain Inventory (BPI) Modified Short Form
|
-2.353 units on a scale
Interval -2.688 to -2.017
|
-2.161 units on a scale
Interval -2.509 to -1.812
|
SECONDARY outcome
Timeframe: Week 8, Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one BPI measurements during Weeks 9-16 (Study Period III).
BPI Modified Short Form worst pain score is a self-reported scale that measures the severity of pain based on the worst pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=170 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change From Week 8 to Week 16 Endpoint in Items of the Brief Pain Inventory (BPI) Modified Short Form Worst Pain Score
|
-2.374 units on a scale
Interval -2.757 to -1.99
|
-2.371 units on a scale
Interval -2.771 to -1.971
|
SECONDARY outcome
Timeframe: Week 8 through Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one BPI measurements during Weeks 9-16 (Study Period III). Last observation carried forward (LOCF) principle was used.
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Outcome measures
| Measure |
Combination
n=165 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=163 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Percentage of Participants With a Reduction of Greater Than or Equal to 30% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint
|
61.8 percentage of participants
|
55.8 percentage of participants
|
SECONDARY outcome
Timeframe: Week 8 through Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one BPI measurements during Weeks 9-16 (Study Period III). Last observation carried forward (LOCF) principle was used.
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Outcome measures
| Measure |
Combination
n=165 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=163 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Percentage of Participants With a Reduction of Greater Than or Equal to 50% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint
|
52.1 percentage of participants
|
39.3 percentage of participants
|
SECONDARY outcome
Timeframe: Week 8 through Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one BPI measurements during Weeks 9-16 (Study Period III). Last observation carried forward (LOCF) principle was used.
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Outcome measures
| Measure |
Combination
n=165 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=163 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Percentage of Participants With a Decrease of Greater Than or Equal to 2 Points on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 16 Endpoint
|
66.7 percentage of participants
|
64.4 percentage of participants
|
SECONDARY outcome
Timeframe: Week 16Population: All randomized participants who received at least one dose of study drug, and had at least one CGI-I measurement during Weeks 9-16 (Study Period III).
Measures clinician's perception of participant improvement at the time of assessment compared with the start of treatment for Study Period III. Scores range from 1 (very much better) to 7 (very much worse). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=170 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Clinical Global Impression of Improvement (CGI-I) at Week 16 Endpoint
|
2.286 units on a scale
Interval 2.127 to 2.444
|
2.359 units on a scale
Interval 2.193 to 2.524
|
SECONDARY outcome
Timeframe: Week 8, Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one NPSI measurements during Weeks 9-16 (Study Period III).
The NPSI is a 12-item self-administered questionnaire to assess 5 different dimensions of neuropathic pain: superficial spontaneous burning pain, deep spontaneous pressing pain, paroxysmal pain, evoked pains, and paresthesias/dysesthesias. A total score ranges from 0 to 100. Higher score indicates a greater intensity of pain. Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=170 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change From Week 8 to Week 16 Endpoint on the Neuropathic Pain Symptom Inventory (NPSI) Questionnaire
|
-13.734 units on a scale
Interval -16.588 to -10.88
|
-11.801 units on a scale
Interval -14.774 to -8.828
|
SECONDARY outcome
Timeframe: Week 8, Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one SDS measurement during Weeks 9-16 (Study Period III). Last observation carried forward (LOCF) principle was used.
The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work (Item 1), social (Item 2), and family life (Item 3). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Total scores is the sum of the 3 items and range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Least Squares (LS) Mean values are controlled for treatment, site, baseline value, treatment\*site and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=108 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=106 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change From Week 8 to Week 16 Endpoint in Sheehan Disability Scale (SDS)
|
-2.625 units on a scale
Interval -3.589 to -1.661
|
-2.431 units on a scale
Interval -3.41 to -1.453
|
SECONDARY outcome
Timeframe: Week 8, Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one HADS measurements during Weeks 9-16 (Study Period III).
A 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and for depression. Scores of 11 or more on either subscale are considered to be a significant case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal.' Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=170 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change From Week 8 to Week 16 Endpoint in Hospital Anxiety and Depression Scale (HADS)
Anxiety Subscale Score (n=169, 169)
|
-0.860 units on a scale
Interval -1.342 to -0.377
|
-0.245 units on a scale
Interval -0.742 to 0.253
|
|
Mean Change From Week 8 to Week 16 Endpoint in Hospital Anxiety and Depression Scale (HADS)
Depression Subscale Score (n=168, 170)
|
-0.461 units on a scale
Interval -0.916 to -0.007
|
-0.083 units on a scale
Interval -0.55 to 0.384
|
SECONDARY outcome
Timeframe: Week 8 through Week 16Population: All randomized participants who received at least one dose of study drug and provided information of hospitalization and sick leave during Weeks 9-16 (Study Period III).
Data presented are the number of days hospitalized and work/school missed (sick leave) due to diabetic peripheral neuropathic pain (DPNP) during the last 8 weeks.
Outcome measures
| Measure |
Combination
n=140 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=146 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Resource Utilization (Number of Days Hospitalized, Number of Days of Sick Leave) Week 8 Through Week 16
Days hospitalized (n=140, 146)
|
0 days
Standard Deviation 0.00
|
0 days
Standard Deviation 0.00
|
|
Resource Utilization (Number of Days Hospitalized, Number of Days of Sick Leave) Week 8 Through Week 16
Days of sick leave (n=41, 36)
|
0.1 days
Standard Deviation 0.65
|
0.4 days
Standard Deviation 2.67
|
SECONDARY outcome
Timeframe: Week 16Population: All randomized participants who received at least one dose of study drug, and at least one PGI-I measurement during Weeks 9-16 (Study Period III).
Measures participant's perception of improvement at the time of assessment compared with the start of treatment for Study Period III. The score ranges from 1 (very much better) to 7 (very much worse). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit, baseline\*visit and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=170 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Patient Global Impression of Improvement (PGI-I) Score at Week 16 Endpoint
|
2.256 units on a scale
Interval 2.085 to 2.426
|
2.350 units on a scale
Interval 2.174 to 2.526
|
SECONDARY outcome
Timeframe: Week 8, Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one BP measurement during Weeks 9-16 (Study Period III). Last observation carried forward (LOCF) principle was used.
Least Squares (LS) mean values are controlled for treatment, site, baseline value, treatment\*site and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=168 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change in Blood Pressure (BP) From Week 8 to Week 16 Endpoint
Systolic BP
|
-1.206 millimeter of mercury (mm Hg)
Interval -3.202 to 0.79
|
0.124 millimeter of mercury (mm Hg)
Interval -1.891 to 2.138
|
|
Mean Change in Blood Pressure (BP) From Week 8 to Week 16 Endpoint
Diastolic BP
|
-0.555 millimeter of mercury (mm Hg)
Interval -1.865 to 0.755
|
-0.551 millimeter of mercury (mm Hg)
Interval -1.873 to 0.771
|
SECONDARY outcome
Timeframe: Week 8, Week 16Population: All randomized participants who received at least one dose of study drug, and had Week 8 and at least one heart rate measurement during Weeks 9- 16 (Study Period III). Last observation carried forward (LOCF) principle was used.
Least Squares (LS) mean values are controlled for treatment, site, baseline value, treatment\*site and treatment in Study Period II.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=168 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change in Heart Rate From Week 8 to Week 16 Endpoint
|
1.025 beats per minute (bpm)
Interval -0.326 to 2.376
|
1.968 beats per minute (bpm)
Interval 0.602 to 3.333
|
SECONDARY outcome
Timeframe: Week 8 through Week 16Population: All randomized participants who received at least one dose of study drug during Weeks 9-16 (Study Period III).
TEAEs in Study Period III are events that began or worsened after Week 8 compared with the period before Week 8.
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=170 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Between Week 8 and Week 16 Endpoint
|
62 participants
|
57 participants
|
SECONDARY outcome
Timeframe: Week 8 through Week 16Population: All randomized participants who received at least one dose of study drug during Weeks 9-16 (Study Period III).
Outcome measures
| Measure |
Combination
n=169 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=170 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Number of Participants Who Discontinued From Study Between Week 8 and Week 16 Endpoint
|
21 participants
|
21 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline BPI measurements during Weeks 1-8 (Study Period II).
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit and baseline\*visit.
Outcome measures
| Measure |
Combination
n=401 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=401 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change From Baseline to Week 8 Endpoint in 24 Hour Average Pain Item Score on the Brief Pain Inventory (BPI) Modified Short Form
|
-2.295 units on a scale
Interval -2.508 to -2.083
|
-1.682 units on a scale
Interval -1.893 to -1.471
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline BPI measurements during Weeks 1-8 (Study Period II). Last observation carried forward (LOCF) principle was used.
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Outcome measures
| Measure |
Combination
n=375 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=374 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Percentage of Participants With a Reduction of Greater Than or Equal to 30% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 8 Endpoint
|
52.0 percentage of participants
|
36.9 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline BPI measurements during Weeks 1-8 (Study Period II). Last observation carried forward (LOCF) principle was used.
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Outcome measures
| Measure |
Combination
n=375 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=374 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Percentage of Participants With a Reduction of Greater Than or Equal to 50% on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 8 Endpoint
|
40.3 percentage of participants
|
27.8 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline BPI measurements during Weeks 1-8 (Study Period II). Last observation carried forward (LOCF) principle was used.
BPI Modified Short Form 24-Hour average pain item score is a self-reported scale that measures the severity of pain based on the average pain experienced over the past 24 hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine).
Outcome measures
| Measure |
Combination
n=375 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=374 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Percentage of Participants With a Decrease of Greater Than or Equal to 2 Points on Brief Pain Inventory (BPI) Modified Short Form 24-Hour Average Pain Item Score at Week 8 Endpoint
|
57.1 percentage of participants
|
45.7 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 8Population: All randomized participants who received at least one dose of study drug, and had at least one post-baseline CGI-I measurement during Weeks 1-8 (Study Period II).
Measures clinician's perception of participant improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, visit, and treatment\*visit.
Outcome measures
| Measure |
Combination
n=400 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=401 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Clinical Global Impression of Improvement (CGI-I) at Week 8 Endpoint
|
2.508 units on a scale
Interval 2.396 to 2.619
|
2.848 units on a scale
Interval 2.737 to 2.959
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline NPSI measurements during Weeks 1-8 (Study Period II).
The NPSI is a 12-item self-administered questionnaire to assess 5 different dimensions of neuropathic pain: superficial spontaneous burning pain, deep spontaneous pressing pain, paroxysmal pain, evoked pains, and paresthesias/dysesthesias. A total score ranges from 0 to 100. Higher score indicates a greater intensity of pain. Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit and baseline\*visit.
Outcome measures
| Measure |
Combination
n=399 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=397 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change From Baseline to Week 8 Endpoint on the Neuropathic Pain Symptom Inventory (NPSI) Questionnaire
|
-19.442 units on a scale
Interval -21.366 to -17.518
|
-14.684 units on a scale
Interval -16.606 to -12.762
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline SDS measurement during Weeks 1-8 (Study Period II). Last observation carried forward (LOCF) principle was used.
The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work (Item 1), social (Item 2), and family life (Item 3). Each item is measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Total scores is the sum of the 3 items and range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Least Squares (LS) mean values are controlled for treatment, site, baseline value and treatment\*site.
Outcome measures
| Measure |
Combination
n=235 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=234 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change From Baseline to Week 8 Endpoint in Sheehan Disability Scale (SDS)
|
-4.387 units on a scale
Interval -5.185 to -3.59
|
-3.367 units on a scale
Interval -4.133 to -2.601
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline HADS measurements during Weeks 1-8 (Study Period II).
A 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for anxiety and for depression. Scores of 11 or more on either subscale are considered to be a significant case of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 represent 'normal.' Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, baseline value, visit, treatment\*visit and baseline\*visit.
Outcome measures
| Measure |
Combination
n=399 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=402 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change From Baseline to Week 8 Endpoint in Hospital Anxiety and Depression Scale (HADS)
Anxiety Subscale Score (n= 398, 400)
|
-1.991 units on a scale
Interval -2.301 to -1.681
|
-1.433 units on a scale
Interval -1.739 to -1.127
|
|
Mean Change From Baseline to Week 8 Endpoint in Hospital Anxiety and Depression Scale (HADS)
Depression Subscale Score
|
-1.064 units on a scale
Interval -1.351 to -0.778
|
-0.642 units on a scale
Interval -0.925 to -0.359
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 8Population: All randomized participants who received at least one dose of study drug and provided information of hospitalization and sick leave during Weeks 1-8 (Study Period II).
Data presented are the number of days hospitalized and work/school missed (sick leave) due to diabetic peripheral neuropathic pain (DPNP) during the last 8 weeks.
Outcome measures
| Measure |
Combination
n=314 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=319 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Resource Utilization (Number of Days Hospitalized, Number of Days of Sick Leave) Baseline Through Week 8
Days hospitalized
|
0 days
Standard Deviation 0.00
|
0 days
Standard Deviation 0.00
|
|
Resource Utilization (Number of Days Hospitalized, Number of Days of Sick Leave) Baseline Through Week 8
Days of sick leave (n=108, 101)
|
1.9 days
Standard Deviation 8.34
|
0.3 days
Standard Deviation 2.04
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 8Population: All randomized participants who received at least one dose of study drug and had worked for pay during Weeks 1-8 (Study Period II).
Data presented are the average number of hours worked for pay per week during the last 8 weeks.
Outcome measures
| Measure |
Combination
n=102 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=100 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Average Number of Hours Worked for Pay Per Week Baseline Through Week 8
|
37.6 hours
Standard Deviation 18.72
|
42.4 hours
Standard Deviation 15.52
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 8 through Week 16Population: All randomized participants who received at least one dose of study drug and had worked for pay during Weeks 9-16 (Study Period III).
Data presented are the average number of hours worked for pay per week during the last 8 weeks.
Outcome measures
| Measure |
Combination
n=42 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=36 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Average Number of Hours Worked for Pay Per Week Week 8 Through Week 16
|
39.8 hours
Standard Deviation 15.98
|
34.7 hours
Standard Deviation 21.46
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 8Population: All randomized participants who received at least one dose of study drug, and at least one post-baseline PGI-I measurement during Weeks 1-8 (Study Period II).
Measures participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). Mixed-effects model repeated measures (MMRM) analysis was used to calculate Least Squares (LS) Mean and 95% Confidence Interval (CI). LS Mean values are controlled for treatment, site, visit, and treatment\*visit.
Outcome measures
| Measure |
Combination
n=401 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=403 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Patient Global Impression of Improvement (PGI-I) Score at Week 8 Endpoint
|
2.601 units on a scale
Interval 2.477 to 2.725
|
2.944 units on a scale
Interval 2.821 to 3.067
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline BP measurement during Week 1-8 (Study Period II). Last observation carried forward (LOCF) principle was used.
Least Squares (LS) mean values are controlled for treatment, site, baseline value, and treatment\*site.
Outcome measures
| Measure |
Combination
n=386 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=389 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change in Blood Pressure (BP) From Baseline to Week 8 Endpoint
Systolic BP
|
-3.702 millimeter of mercury (mm Hg)
Interval -5.216 to -2.188
|
-1.682 millimeter of mercury (mm Hg)
Interval -3.191 to -0.174
|
|
Mean Change in Blood Pressure (BP) From Baseline to Week 8 Endpoint
Diastolic BP
|
-0.816 millimeter of mercury (mm Hg)
Interval -1.766 to 0.134
|
-0.951 millimeter of mercury (mm Hg)
Interval -1.898 to -0.003
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Week 8Population: All randomized participants who received at least one dose of study drug, and had baseline and at least one post-baseline heart rate measurement during Weeks 1-8 (Study Period II). Last observation carried forward (LOCF) principle was used.
Least Squares (LS) mean values are controlled for treatment, site, baseline value, and treatment\*site.
Outcome measures
| Measure |
Combination
n=384 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=389 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Mean Change in Heart Rate From Baseline to Week 8 Endpoint
|
0.839 beats per minute (bpm)
Interval -0.062 to 1.741
|
-2.478 beats per minute (bpm)
Interval -3.369 to -1.588
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 8Population: All randomized participants who received at least one dose of study drug during Weeks 1-8 (Study Period II).
TEAEs in Study Period II are events that began or worsened after Week 0 compared with the period before Week 0.
Outcome measures
| Measure |
Combination
n=401 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=403 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE) Between Baseline and Week 8 Endpoint
|
223 participants
|
232 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline through Week 8Population: All randomized participants who received at least one dose of study drug during Weeks 1-8 (Study Period II).
Outcome measures
| Measure |
Combination
n=401 Participants
All participants who received Duloxetine Combination therapy (Duloxetine 60 milligram \[mg\] plus Pregabalin 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16) or Pregabalin Combination therapy (Pregabalin 300 mg plus Duloxetine 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
Monotherapy
n=403 Participants
All participants who received Duloxetine Monotherapy (Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16) or Pregabalin Monotherapy (Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16) in Study Period III were pooled together.
|
|---|---|---|
|
Number of Participants Who Discontinued From Study Between Baseline and Week 8 Endpoint
|
68 participants
|
70 participants
|
Adverse Events
Duloxetine (SP II)
Serious events: 12 serious events
Other events: 216 other events
Deaths: 0 deaths
Pregabalin (SP II)
Serious events: 13 serious events
Other events: 225 other events
Deaths: 0 deaths
Duloxetine (SP III)
Serious events: 3 serious events
Other events: 18 other events
Deaths: 0 deaths
DLX + PGB (SP III)
Serious events: 3 serious events
Other events: 21 other events
Deaths: 0 deaths
PGB + DLX (SP III)
Serious events: 5 serious events
Other events: 39 other events
Deaths: 0 deaths
Pregabalin (SP III)
Serious events: 2 serious events
Other events: 37 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Duloxetine (SP II)
n=401 participants at risk
Duloxetine 30 milligram (mg) daily for Week 1 and 60 mg daily for Weeks 2-8 in Study Period II (SP II).
|
Pregabalin (SP II)
n=403 participants at risk
Pregabalin 150 mg daily for Week 1 and 300 mg daily for Weeks 2-8 in Study Period II.
|
Duloxetine (SP III)
n=73 participants at risk
Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16 in Study Period III (SP III).
|
DLX + PGB (SP III)
n=75 participants at risk
Duloxetine (DLX) 60 mg plus Pregabalin (PGB) 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16 in Study Period III.
|
PGB + DLX (SP III)
n=94 participants at risk
Pregabalin (PGB) 300 mg plus Duloxetine (DLX) 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16 in Study Period III.
|
Pregabalin (SP III)
n=97 participants at risk
Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16 in Study Period III.
|
|---|---|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Gastrointestinal disorders
Duodenal ulcer
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Gastrointestinal disorders
Duodenitis
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Gastritis
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
General disorders
Chest pain
|
0.25%
1/401 • Number of events 1
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
General disorders
Hernia
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Infections and infestations
Cellulitis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Erysipelas
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Infections and infestations
Gastrointestinal infection
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Pilonidal cyst
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Pneumonia
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Respiratory tract infection viral
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Viral infection
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Injury, poisoning and procedural complications
Brain contusion
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Investigations
Haemoglobin decreased
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Investigations
Hepatitis c antibody positive
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/401
|
0.74%
3/403 • Number of events 3
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large intestine carcinoma
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Nervous system disorders
Myelitis transverse
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Nervous system disorders
Presyncope
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Psychiatric disorders
Confusional state
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Psychiatric disorders
Disorientation
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Psychiatric disorders
Hallucination
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Psychiatric disorders
Suicidal ideation
|
0.00%
0/401
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Vascular disorders
Hypertension
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Vascular disorders
Hypertensive crisis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
Other adverse events
| Measure |
Duloxetine (SP II)
n=401 participants at risk
Duloxetine 30 milligram (mg) daily for Week 1 and 60 mg daily for Weeks 2-8 in Study Period II (SP II).
|
Pregabalin (SP II)
n=403 participants at risk
Pregabalin 150 mg daily for Week 1 and 300 mg daily for Weeks 2-8 in Study Period II.
|
Duloxetine (SP III)
n=73 participants at risk
Duloxetine 90 mg daily for Week 9 and 120 mg daily for Weeks 10-16 in Study Period III (SP III).
|
DLX + PGB (SP III)
n=75 participants at risk
Duloxetine (DLX) 60 mg plus Pregabalin (PGB) 150 mg daily for Week 9 and Duloxetine 60 mg plus Pregabalin 300 mg daily for Weeks 10-16 in Study Period III.
|
PGB + DLX (SP III)
n=94 participants at risk
Pregabalin (PGB) 300 mg plus Duloxetine (DLX) 30 mg daily for Week 9 and Pregabalin 300 mg plus Duloxetine 60 mg daily for Weeks 10-16 in Study Period III.
|
Pregabalin (SP III)
n=97 participants at risk
Pregabalin 450 mg daily for Week 9 and Pregabalin 600 mg daily for Weeks 10-16 in Study Period III.
|
|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 2
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/401
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Cardiac disorders
Cardiac failure chronic
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Cardiac disorders
Palpitations
|
1.00%
4/401 • Number of events 4
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Cardiac disorders
Tachycardia
|
1.00%
4/401 • Number of events 4
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Ear and labyrinth disorders
Hearing impaired
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Ear and labyrinth disorders
Vertigo
|
2.0%
8/401 • Number of events 8
|
6.5%
26/403 • Number of events 27
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Endocrine disorders
Hyperthyroidism
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Eye disorders
Eyelid oedema
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Eye disorders
Vision blurred
|
1.2%
5/401 • Number of events 6
|
0.74%
3/403 • Number of events 3
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Eye disorders
Visual impairment
|
0.50%
2/401 • Number of events 2
|
0.25%
1/403 • Number of events 1
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.50%
2/401 • Number of events 2
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
2.1%
2/94 • Number of events 2
|
0.00%
0/97
|
|
Gastrointestinal disorders
Abdominal pain upper
|
1.2%
5/401 • Number of events 5
|
0.74%
3/403 • Number of events 3
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Gastrointestinal disorders
Chapped lips
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Constipation
|
4.0%
16/401 • Number of events 17
|
3.2%
13/403 • Number of events 14
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
3.5%
14/401 • Number of events 14
|
2.7%
11/403 • Number of events 12
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
3.1%
3/97 • Number of events 3
|
|
Gastrointestinal disorders
Dry mouth
|
4.0%
16/401 • Number of events 17
|
2.2%
9/403 • Number of events 11
|
2.7%
2/73 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
2.1%
2/94 • Number of events 2
|
0.00%
0/97
|
|
Gastrointestinal disorders
Dyspepsia
|
1.00%
4/401 • Number of events 4
|
0.99%
4/403 • Number of events 4
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Gastrointestinal disorders
Flatulence
|
1.00%
4/401 • Number of events 4
|
1.2%
5/403 • Number of events 5
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Gastrointestinal disorders
Gastritis
|
1.2%
5/401 • Number of events 5
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.50%
2/401 • Number of events 2
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Gastrointestinal disorders
Nausea
|
14.2%
57/401 • Number of events 61
|
6.2%
25/403 • Number of events 26
|
2.7%
2/73 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
4.3%
4/94 • Number of events 4
|
1.0%
1/97 • Number of events 1
|
|
Gastrointestinal disorders
Paraesthesia oral
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Gastrointestinal disorders
Vomiting
|
3.0%
12/401 • Number of events 13
|
1.5%
6/403 • Number of events 7
|
0.00%
0/73
|
0.00%
0/75
|
4.3%
4/94 • Number of events 4
|
1.0%
1/97 • Number of events 1
|
|
General disorders
Asthenia
|
1.5%
6/401 • Number of events 8
|
1.7%
7/403 • Number of events 7
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
General disorders
Chest discomfort
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
General disorders
Chest pain
|
0.50%
2/401 • Number of events 2
|
0.74%
3/403 • Number of events 3
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
General disorders
Discomfort
|
0.50%
2/401 • Number of events 2
|
0.25%
1/403 • Number of events 1
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
General disorders
Facial pain
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
General disorders
Fatigue
|
4.5%
18/401 • Number of events 18
|
3.2%
13/403 • Number of events 13
|
2.7%
2/73 • Number of events 2
|
1.3%
1/75 • Number of events 1
|
2.1%
2/94 • Number of events 2
|
1.0%
1/97 • Number of events 1
|
|
General disorders
Gait disturbance
|
0.25%
1/401 • Number of events 1
|
0.99%
4/403 • Number of events 4
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
General disorders
Oedema
|
0.25%
1/401 • Number of events 1
|
1.7%
7/403 • Number of events 7
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
General disorders
Oedema peripheral
|
1.00%
4/401 • Number of events 5
|
5.2%
21/403 • Number of events 23
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
2.1%
2/97 • Number of events 2
|
|
General disorders
Pain
|
0.50%
2/401 • Number of events 2
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
General disorders
Therapeutic response unexpected
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Bronchitis
|
0.00%
0/401
|
0.74%
3/403 • Number of events 3
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
1.1%
1/94 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Cystitis
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Erysipelas
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Infections and infestations
Gastroenteritis
|
0.25%
1/401 • Number of events 1
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Gastroenteritis viral
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Infection
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Influenza
|
0.25%
1/401 • Number of events 1
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
0.75%
3/401 • Number of events 3
|
1.2%
5/403 • Number of events 5
|
0.00%
0/73
|
0.00%
0/75
|
2.1%
2/94 • Number of events 3
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Onychomycosis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/401
|
0.50%
2/403 • Number of events 2
|
1.4%
1/73 • Number of events 1
|
1.3%
1/75 • Number of events 1
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Infections and infestations
Pneumonia
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Upper respiratory tract infection
|
0.25%
1/401 • Number of events 1
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/401
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 2
|
|
Injury, poisoning and procedural complications
Concussion
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/401
|
0.74%
3/403 • Number of events 3
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.25%
1/401 • Number of events 1
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Injury, poisoning and procedural complications
Laceration
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Injury, poisoning and procedural complications
Muscle rupture
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Injury, poisoning and procedural complications
Subcutaneous haematoma
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
2.1%
2/97 • Number of events 2
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Investigations
Visual acuity tests abnormal
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Investigations
Vitamin b12 decreased
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Investigations
Weight increased
|
0.50%
2/401 • Number of events 2
|
2.2%
9/403 • Number of events 9
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
3.1%
3/97 • Number of events 3
|
|
Metabolism and nutrition disorders
Decreased appetite
|
4.2%
17/401 • Number of events 18
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.50%
2/401 • Number of events 2
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.00%
4/401 • Number of events 7
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
3.1%
3/97 • Number of events 3
|
|
Metabolism and nutrition disorders
Increased appetite
|
0.00%
0/401
|
1.5%
6/403 • Number of events 6
|
1.4%
1/73 • Number of events 1
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.75%
3/401 • Number of events 4
|
0.99%
4/403 • Number of events 4
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
1.1%
1/94 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.75%
3/401 • Number of events 3
|
1.2%
5/403 • Number of events 6
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
2.1%
2/97 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
0.25%
1/401 • Number of events 1
|
0.74%
3/403 • Number of events 3
|
0.00%
0/73
|
0.00%
0/75
|
2.1%
2/94 • Number of events 2
|
0.00%
0/97
|
|
Musculoskeletal and connective tissue disorders
Muscle contracture
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
1.00%
4/401 • Number of events 5
|
0.50%
2/403 • Number of events 2
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/401
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.75%
3/401 • Number of events 3
|
0.74%
3/403 • Number of events 4
|
4.1%
3/73 • Number of events 3
|
4.0%
3/75 • Number of events 3
|
2.1%
2/94 • Number of events 3
|
0.00%
0/97
|
|
Musculoskeletal and connective tissue disorders
Plantar fasciitis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 2
|
|
Nervous system disorders
Amnesia
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Nervous system disorders
Balance disorder
|
1.00%
4/401 • Number of events 5
|
1.7%
7/403 • Number of events 7
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
2.1%
2/97 • Number of events 2
|
|
Nervous system disorders
Disturbance in attention
|
0.50%
2/401 • Number of events 2
|
1.7%
7/403 • Number of events 8
|
0.00%
0/73
|
0.00%
0/75
|
2.1%
2/94 • Number of events 2
|
1.0%
1/97 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
7.2%
29/401 • Number of events 36
|
15.1%
61/403 • Number of events 69
|
5.5%
4/73 • Number of events 5
|
2.7%
2/75 • Number of events 2
|
2.1%
2/94 • Number of events 2
|
2.1%
2/97 • Number of events 2
|
|
Nervous system disorders
Dysaesthesia
|
0.25%
1/401 • Number of events 1
|
0.25%
1/403 • Number of events 1
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Nervous system disorders
Dysarthria
|
0.25%
1/401 • Number of events 1
|
0.50%
2/403 • Number of events 3
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Nervous system disorders
Headache
|
4.7%
19/401 • Number of events 21
|
3.2%
13/403 • Number of events 15
|
4.1%
3/73 • Number of events 3
|
0.00%
0/75
|
1.1%
1/94 • Number of events 4
|
0.00%
0/97
|
|
Nervous system disorders
Hypoaesthesia
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
2.7%
2/75 • Number of events 2
|
0.00%
0/94
|
0.00%
0/97
|
|
Nervous system disorders
Hypotonia
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Nervous system disorders
Lethargy
|
1.7%
7/401 • Number of events 7
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Nervous system disorders
Migraine with aura
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Nervous system disorders
Neuralgia
|
0.50%
2/401 • Number of events 2
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
2.1%
2/97 • Number of events 2
|
|
Nervous system disorders
Paraesthesia
|
0.25%
1/401 • Number of events 1
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Nervous system disorders
Psychomotor skills impaired
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Nervous system disorders
Sciatica
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Nervous system disorders
Sedation
|
0.75%
3/401 • Number of events 3
|
0.74%
3/403 • Number of events 5
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Nervous system disorders
Sensory loss
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Nervous system disorders
Somnolence
|
10.0%
40/401 • Number of events 46
|
10.9%
44/403 • Number of events 50
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
2.1%
2/94 • Number of events 2
|
5.2%
5/97 • Number of events 5
|
|
Nervous system disorders
Syncope
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.75%
3/401 • Number of events 3
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Apathy
|
0.50%
2/401 • Number of events 2
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Delirium
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Psychiatric disorders
Depression
|
0.00%
0/401
|
0.99%
4/403 • Number of events 6
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Dissociation
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Psychiatric disorders
Insomnia
|
2.0%
8/401 • Number of events 8
|
0.99%
4/403 • Number of events 4
|
1.4%
1/73 • Number of events 1
|
2.7%
2/75 • Number of events 2
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Libido decreased
|
0.50%
2/401 • Number of events 2
|
1.2%
5/403 • Number of events 5
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
0.00%
0/97
|
|
Psychiatric disorders
Loss of libido
|
0.25%
1/401 • Number of events 1
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Mood swings
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Paranoia
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Psychiatric disorders
Sleep disorder
|
1.5%
6/401 • Number of events 6
|
1.5%
6/403 • Number of events 6
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Renal and urinary disorders
Dysuria
|
2.2%
9/401 • Number of events 9
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
2.1%
2/97 • Number of events 2
|
|
Renal and urinary disorders
Urinary hesitation
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Renal and urinary disorders
Urine flow decreased
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
1.5%
6/401 • Number of events 6
|
0.99%
4/403 • Number of events 4
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.50%
2/401 • Number of events 2
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.25%
1/401 • Number of events 1
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Ecchymosis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/401
|
0.50%
2/403 • Number of events 2
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
4.0%
16/401 • Number of events 16
|
0.99%
4/403 • Number of events 4
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
1.0%
1/97 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
0.00%
0/401
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.25%
1/401 • Number of events 1
|
0.00%
0/403
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.25%
1/401 • Number of events 2
|
0.74%
3/403 • Number of events 3
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.75%
3/401 • Number of events 3
|
0.25%
1/403 • Number of events 1
|
1.4%
1/73 • Number of events 2
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
1.3%
1/75 • Number of events 1
|
0.00%
0/94
|
2.1%
2/97 • Number of events 3
|
|
Vascular disorders
Arteriosclerosis
|
0.75%
3/401 • Number of events 3
|
1.5%
6/403 • Number of events 6
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Vascular disorders
Hypertension
|
1.7%
7/401 • Number of events 7
|
0.74%
3/403 • Number of events 3
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Vascular disorders
Hypotension
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
1.4%
1/73 • Number of events 1
|
0.00%
0/75
|
0.00%
0/94
|
0.00%
0/97
|
|
Vascular disorders
Phlebitis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/401
|
0.00%
0/403
|
0.00%
0/73
|
0.00%
0/75
|
0.00%
0/94
|
1.0%
1/97 • Number of events 1
|
|
Vascular disorders
Venous insufficiency
|
0.00%
0/401
|
0.25%
1/403 • Number of events 1
|
0.00%
0/73
|
0.00%
0/75
|
1.1%
1/94 • Number of events 1
|
0.00%
0/97
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60