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A Study of Duloxetine (LY248686) in Participants With Chronic Low Back Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01855919
Recruitment Status : Completed
First Posted : May 17, 2013
Results First Posted : July 23, 2015
Last Update Posted : July 23, 2015
Sponsor:
Collaborator:
Shionogi
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Back Pain Lower Back Chronic
Interventions Drug: Duloxetine
Drug: Placebo
Enrollment 458

Recruitment Details  
Pre-assignment Details The participant flow includes information on participants who completed the study. 2 participants who were assigned to receive placebo received duloxetine instead. These participants were treated as placebo in efficacy analysis and as duloxetine in safety analysis. In the participant flow, these participants are included under placebo.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description Duloxetine 20 milligram (mg) during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15. Placebo administered in capsule form orally once every day for 15 weeks.
Period Title: Overall Study
Started 232 226
Received at Least 1 Dose of Study Drug 232 226
Completed 209 200
Not Completed 23 26
Reason Not Completed
Adverse Event             16             8
Lack of Efficacy             1             3
Withdrawal by Subject             4             10
Entry Criteria Not Met             1             1
Protocol Violation             1             4
Arm/Group Title Duloxetine Placebo Total
Hide Arm/Group Description Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15. Placebo administered in capsule form orally once every day for 15 weeks. Total of all reporting groups
Overall Number of Baseline Participants 230 226 456
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose Brief Pain Inventory (BPI) pain severity (average pain) scores.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 230 participants 226 participants 456 participants
60.0  (13.2) 57.8  (13.7) 58.9  (13.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 226 participants 456 participants
Female
115
  50.0%
122
  54.0%
237
  52.0%
Male
115
  50.0%
104
  46.0%
219
  48.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 226 participants 456 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
230
 100.0%
226
 100.0%
456
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 226 participants 456 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
230
 100.0%
226
 100.0%
456
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 230 participants 226 participants 456 participants
230 226 456
1.Primary Outcome
Title Change From Baseline to Week 14 in Brief Pain Inventory (BPI) 24-Hour Average Pain Severity Item
Hide Description BPI is a self-reported scale that measures the severity of pain based on the average pain during the past 24-hours. The severity scores ranged from 0 (no pain) to 10 (pain as severe as you can imagine). Higher scores indicated worsening of pain. Least squares (LS) means calculated using mixed model repeating measure (MMRM) adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.43  (0.11) -1.96  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.46
Confidence Interval (2-Sided) 95%
-0.77 to -0.16
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Patient Global Impression of Improvement (PGI-I) at Week 14
Hide Description PGI-I measures a participant's perception of improvement at the time of assessment compared with the start of treatment. Score ranges from 1 (very much better) to 7 (very much worse). LS means calculated using MMRM adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.
Time Frame Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
2.46  (0.07) 2.76  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0026
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.48 to -0.10
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Roland Morris Disability Questionnaire (RMDQ-24) to Week 14
Hide Description The RMDQ-24 is a health status measure completed by participants to assess physical disability due to low back pain. Participants answered 24 questions about impairment of daily living activities (standing, walking, sitting, wearing clothes, working, etc.) resulting from low back pain. The number of statements marked was summed by the clinician for a total score. The total scores range from 0 (no disability) to 24 (severe disability). LS means calculated using analysis of covariance (ANCOVA) with treatment group as a fixed effect, and baseline value as a covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. The last observation carried forward (LOCF) was used.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.86  (0.22) -3.23  (0.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0439
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-1.25 to -0.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in BPI Pain Severity Items (BPI-S) and Interference Items (BPI-I) Scores to Week 14
Hide Description BPI-S and BPI-I are self-reported scales measuring severity of pain and interference on function. Severity scores range from: 0 (no pain) to 10 (severe pain) on each question assessing worst pain, least pain, and average pain in past 24 hours, and pain right now. Interference scores range from: 0 (does not interfere) to 10 (completely interferes) on each question assessing interference of pain in past 24 hours for general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life. Average interference is defined as the average of non-missing scores of individual interference items. Higher scores indicated worsening of pain. LS means calculated using MMRM adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Worst Pain -2.63  (0.13) -2.33  (0.13)
Least Pain -1.69  (0.10) -1.19  (0.11)
Current Pain -2.42  (0.12) -2.03  (0.12)
General Activity -2.46  (0.13) -2.16  (0.13)
Mood -2.15  (0.11) -1.83  (0.11)
Walking Ability -2.05  (0.11) -1.92  (0.11)
Normal Work -2.17  (0.12) -2.17  (0.12)
Relationship People -1.02  (0.10) -0.98  (0.10)
Sleep -1.41  (0.11) -1.40  (0.11)
Enjoyment of Life -1.52  (0.11) -1.48  (0.11)
Average of 7 Interference Items -1.83  (0.10) -1.70  (0.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1010
Comments p-value is for worst pain
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.66 to 0.06
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments p-value is for least pain
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.79 to -0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0230
Comments p-value is for Pain Right Now
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.74 to -0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0874
Comments p-value is for General Activity
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.66 to 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0436
Comments p-value is for Mood
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.63 to -0.01
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3902
Comments p-value is for Walking Ability
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.14
Confidence Interval (2-Sided) 95%
-0.45 to 0.18
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9910
Comments p-value is for Normal Work
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.33 to 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7848
Comments p-value is for Relationship People
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.30 to 0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9424
Comments p-value is for Sleep
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.32 to 0.30
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7932
Comments p-value is for Enjoyment of Life
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.35 to 0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3761
Comments p-value is for Average of 7 Items
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.40 to 0.15
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Weekly Mean of 24 Hour Average Pain and Worst Daily Pain Severity Scores to Week 14
Hide Description 24-hour average pain severity scores were recorded daily on an 11-point Likert scale, an ordinal scale, with scores ranging from 0 (no pain) to 10 (worst possible pain). The 11-point Likert scale was also used for assessment of average pain and worst pain within 24-hours. For the analysis, weekly mean was calculated. LS means calculated using MMRM adjusted for treatment, week, interaction between treatment and week as fixed effects and baseline value as covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Average Pain -2.15  (0.10) -1.73  (0.11)
Worst Pain -2.25  (0.12) -1.91  (0.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0049
Comments p-value is for Average Pain
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.71 to -0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0442
Comments p-value is for Worst pain
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.69 to -0.01
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Reduction of ≥30% and ≥50% in BPI Average Pain Score at Week 14
Hide Description Pain severity was measured using an 11 point BPI scale from 0 (no pain) to 10 (worst pain) to determine average pain in the past 24 hours (average pain). A 30% (or 50%) improvement was defined as a ≥30% (or ≥50%) reduction in BPI pain severity from baseline to endpoint. Percentage of participants = (number of participants with ≥30% or ≥50% pain reduction / total number of participants in treatment group) * 100.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Measure Type: Number
Unit of Measure: percentage of participants
≥30% pain reduction 68.7 52.2
≥50% pain reduction 56.5 39.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments p-value is for ≥30%
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
1.13 to 1.53
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments p-value is for ≥50%
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
1.18 to 1.75
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With Sustained Pain Reduction in BPI Average Pain Score
Hide Description Pain severity was measured using an 11 point BPI scale from 0 (no pain) to 10(worst pain) to determine average pain in the past 24 hours (average pain). Participants were considered to have sustained pain reduction of ≥30% in the BPI-severity score (average pain) at the time of final evaluation and at least 1 other time point prior to the time of final evaluation compared with baseline, and a reduction of ≥20% from baseline sustained at all evaluation time points between that period. Percentage of participants = (number of participants with sustained pain reduction / total number of participants in treatment group) * 100.
Time Frame Baseline through Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Measure Type: Number
Unit of Measure: percentage of participants
61.3 46.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method Mantel Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 1.33
Confidence Interval (2-Sided) 95%
1.12 to 1.58
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Clinical Global Impression of Severity (CGI-Severity) to Week 14
Hide Description CSI-S measures severity of illness at the time of assessment compared with start of treatment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). LS means calculated using MMRM adjusted for treatment, visit, interaction between treatment and visit as fixed effects and baseline value as covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.46  (0.06) -1.17  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.46 to -0.10
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Beck Depression Inventory-II (BDI-II) to Week 14
Hide Description BDI-II is a 21-question multiple-choice self-reported inventory about depressive symptoms (sadness, pessimism, past failure, loss of pleasure, guilty feelings, punishment feelings, self-dislike, self-criticalness, suicidal thoughts or wishes, crying, agitation, loss of interest, indecisiveness, worthlessness, loss of energy, changes in sleeping patterns, irritability, changes in appetite, concentration difficulties, tiredness or fatigue, and loss of interest in sex). The scores for each item range from 0 (best) to 3 (worst) with possible total scores of 0 to 63, where higher total scores indicate more severe depressive symptoms. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-1.39  (0.24) -1.04  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3012
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-1.03 to 0.32
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in 36-Item Short-Form Health Survey (SF-36) to Week 14
Hide Description SF-36 Health Status Survey is a generic, health-related scale assessing participant’s quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 milligram (mg) for first week, 40 mg for second week and 60 mg for next 12 weeks administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during the last week.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Physical Functioning 8.47  (0.79) 7.20  (0.80)
Role (Physical) 10.58  (1.15) 10.00  (1.16)
Bodily Pain 12.56  (0.94) 11.01  (0.95)
General Health 6.72  (0.85) 3.78  (0.86)
Vitality 5.56  (0.97) 4.41  (0.97)
Social Functioning 6.40  (1.00) 4.77  (1.01)
Role (Emotional) 5.78  (1.13) 6.18  (1.14)
Mental Health 5.63  (0.81) 2.42  (0.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2581
Comments p-value for Physical Functioning
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
-0.93 to 3.47
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7208
Comments p-value for Role (Physical)
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
-2.62 to 3.79
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2487
Comments p-value for Bodily Pain
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
-1.09 to 4.19
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0151
Comments p-value for General Health
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.94
Confidence Interval (2-Sided) 95%
0.57 to 5.31
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4000
Comments p-value for Vitality
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
-1.54 to 3.85
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2529
Comments p-value for Social Functioning
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.63
Confidence Interval (2-Sided) 95%
-1.17 to 4.43
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8042
Comments p-value for Role(Emotional)
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-3.55 to 2.75
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0058
Comments p-value is for Mental Health
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.21
Confidence Interval (2-Sided) 95%
0.94 to 5.48
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in European Quality of Life Questionnaire-5 Dimension (EQ-5D) to Week 14
Hide Description The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3 level scale (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the Japan population-based algorithm ranging from -0.111 to 1.0, with higher scores indicating better quality of life. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had baseline and at least 1 post-dose BPI pain severity (average pain) scores. LOCF.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.09  (0.01) 0.08  (0.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5237
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.02 to 0.03
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Work Productivity and Activity Impairment (WPAI) Instrument to Week 14
Hide Description WPAI is a self-administered instrument used to measure effect of general health and symptom severity on work productivity and regular activities, and yields 4 types of scores: Absenteeism (work time missed)=Question (Q)2/(Q2+4))*100); Presenteeism (impairment at work/reduced on-the-job effectiveness)=(Q5/10)*100); Work Productivity Loss (overall work impairment/absenteeism plus presenteeism)=(Q2/(Q2+Q4)+[(1-Q2/(Q2+Q4))x(Q5/10)])*100); and Activity Impairment=(Q6/10)*100. Scores range from 0 to 1 for each of the above 4 types; higher scores indicate greater impairment. LS means calculated using ANCOVA adjusted for treatment, as fixed effect and baseline as covariate.
Time Frame Baseline, Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: All randomized participants who received at least 1 dose of study drug and had at least 1 post-dose BPI pain severity (average pain) scores. LOCF was used.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 230 226
Least Squares Mean (Standard Error)
Unit of Measure: hours
Work time missed (n=135, 140) -0.01  (0.01) 0.02  (0.01)
Impairment at work (n=136, 140) -0.13  (0.02) -0.09  (0.02)
Work productivity loss (n=135, 140) -0.13  (0.02) -0.09  (0.02)
Work activity impairment (n=230, 226) -0.14  (0.01) -0.12  (0.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0460
Comments p-value for Work time missed
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.05 to 0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0753
Comments p-value for Impairment at work
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.08 to 0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0795
Comments p-value for Work productivity loss
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.08 to 0.00
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Duloxetine, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1466
Comments p-value for Work activity impairment
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.06 to 0.01
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Number of Participants With Suicidal Thoughts And Behaviors During Study [Columbia Suicide Severity Rating Scale (C-SSRS)]
Hide Description C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any 1 of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any 1 of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.
Time Frame Baseline through Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug, responded no at baseline to the suicide related questionnaire and had data at post-treatment for each question.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 232 224
Measure Type: Number
Unit of Measure: percentage of participants
Wish to be dead (n=226, 220) 0 0
Nonspecific active suicidal thoughts (n=231, 223) 0 0
Suicidal behavior (n=232, 224) 0 0
14.Secondary Outcome
Title Percentage of Participants With Fall Events in Fall Questionnaire
Hide Description Participants evaluated their experience with and details of falls which were recorded. Percentage = (number of participants with fall events) /(total in treatment group) * 100.
Time Frame Baseline through Week 14
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study drug.
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description:
Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15.
Placebo administered in capsule form orally once every day for 15 weeks.
Overall Number of Participants Analyzed 234 224
Measure Type: Number
Unit of Measure: percentage of participants
10.3 8.0
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Duloxetine Placebo
Hide Arm/Group Description Duloxetine 20 mg during Week 1, 40 mg during Week 2, and 60 mg during Weeks 3 to 14 administered in capsule form orally once daily. Tapering doses of 40 mg for first 3 days and 20 mg for last 4 days were administered during Week 15. Placebo administered in capsule form orally once every day for 15 weeks.
All-Cause Mortality
Duloxetine Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Duloxetine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/234 (1.71%)      4/224 (1.79%)    
Gastrointestinal disorders     
Gastric polyps  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Infections and infestations     
Pneumonia bacterial  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Pneumonia pneumococcal  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Musculoskeletal and connective tissue disorders     
Intervertebral disc protrusion  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Osteoarthritis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Nervous system disorders     
Cerebral haemorrhage  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Renal and urinary disorders     
Calculus urethral  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Haemothorax  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Duloxetine Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   167/234 (71.37%)      134/224 (59.82%)    
Blood and lymphatic system disorders     
Idiopathic thrombocytopenic purpura  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Cardiac disorders     
Bundle branch block right  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Palpitations  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Supraventricular extrasystoles  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Tachycardia  1  2/234 (0.85%)  2 0/224 (0.00%)  0
Ear and labyrinth disorders     
Motion sickness  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Tinnitus  1  2/234 (0.85%)  2 1/224 (0.45%)  1
Vertigo  1  5/234 (2.14%)  5 0/224 (0.00%)  0
Vertigo positional  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Endocrine disorders     
Autoimmune thyroiditis  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Eye disorders     
Conjunctivitis  1  2/234 (0.85%)  2 0/224 (0.00%)  0
Conjunctivitis allergic  1  2/234 (0.85%)  2 1/224 (0.45%)  1
Eye pain  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Eyelid ptosis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Photophobia  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Vision blurred  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Gastrointestinal disorders     
Abdominal discomfort  1  8/234 (3.42%)  8 3/224 (1.34%)  4
Abdominal distension  1  3/234 (1.28%)  3 1/224 (0.45%)  1
Abdominal pain  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Abdominal pain upper  1  2/234 (0.85%)  2 2/224 (0.89%)  2
Cheilitis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Constipation  1  25/234 (10.68%)  25 5/224 (2.23%)  5
Dental caries  1  4/234 (1.71%)  4 2/224 (0.89%)  2
Diarrhoea  1  9/234 (3.85%)  10 1/224 (0.45%)  1
Dyspepsia  1  4/234 (1.71%)  4 1/224 (0.45%)  1
Enterocolitis  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Gastritis  1  2/234 (0.85%)  2 1/224 (0.45%)  1
Gastritis atrophic  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Gastrointestinal motility disorder  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Gastrooesophageal reflux disease  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Haemorrhoids  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Hypoaesthesia oral  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Infrequent bowel movements  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Inguinal hernia  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Large intestine polyp  1  2/234 (0.85%)  2 0/224 (0.00%)  0
Nausea  1  21/234 (8.97%)  21 6/224 (2.68%)  6
Saliva altered  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Stomatitis  1  2/234 (0.85%)  2 0/224 (0.00%)  0
Vomiting  1  1/234 (0.43%)  1 0/224 (0.00%)  0
General disorders     
Asthenia  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Calcinosis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Chest pain  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Face oedema  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Feeling abnormal  1  2/234 (0.85%)  3 1/224 (0.45%)  1
Malaise  1  8/234 (3.42%)  9 3/224 (1.34%)  3
Oedema peripheral  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Thirst  1  14/234 (5.98%)  14 0/224 (0.00%)  0
Hepatobiliary disorders     
Hepatic function abnormal  1  2/234 (0.85%)  2 0/224 (0.00%)  0
Infections and infestations     
Acute tonsillitis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Bronchitis  1  7/234 (2.99%)  7 2/224 (0.89%)  2
Enteritis infectious  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Gastroenteritis  1  3/234 (1.28%)  3 1/224 (0.45%)  1
Gingival abscess  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Gingival infection  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Gingivitis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Hordeolum  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Infected dermal cyst  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Influenza  1  1/234 (0.43%)  1 3/224 (1.34%)  3
Nasopharyngitis  1  26/234 (11.11%)  33 39/224 (17.41%)  43
Oral herpes  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Otitis externa  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Otitis media chronic  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Periodontitis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Pertussis  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Pharyngitis  1  3/234 (1.28%)  3 0/224 (0.00%)  0
Pulpitis dental  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Purulence  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Subcutaneous abscess  1  0/234 (0.00%)  0 1/224 (0.45%)  2
Tinea pedis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Tonsillitis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Upper respiratory tract infection  1  2/234 (0.85%)  2 2/224 (0.89%)  3
Injury, poisoning and procedural complications     
Bone contusion  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Chillblains  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Contusion  1  16/234 (6.84%)  18 7/224 (3.13%)  8
Epicondylitis  1  0/234 (0.00%)  0 2/224 (0.89%)  2
Excoriation  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Fall  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Heat illness  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Joint dislocation  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Laceration  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Ligament injury  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Ligament sprain  1  5/234 (2.14%)  5 1/224 (0.45%)  1
Nerve root injury cervical  1  2/234 (0.85%)  2 0/224 (0.00%)  0
Post-traumatic neck syndrome  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Procedural pain  1  4/234 (1.71%)  5 2/224 (0.89%)  2
Radius fracture  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Rib fracture  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Spinal compression fracture  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Stab wound  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Thermal burn  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Wound  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Investigations     
Alanine aminotransferase increased  1  4/234 (1.71%)  4 0/224 (0.00%)  0
Aspartate aminotransferase increased  1  3/234 (1.28%)  3 0/224 (0.00%)  0
Blood bilirubin increased  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Blood creatine phosphokinase increased  1  4/234 (1.71%)  4 3/224 (1.34%)  3
Blood creatinine increased  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Blood lactate dehydrogenase increased  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Blood triglycerides increased  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Blood urea increased  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Blood urine present  1  1/234 (0.43%)  1 2/224 (0.89%)  2
Gamma-glutamyltransferase increased  1  2/234 (0.85%)  2 1/224 (0.45%)  1
Glucose urine present  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Liver function test abnormal  1  6/234 (2.56%)  6 3/224 (1.34%)  3
Platelet count increased  1  0/234 (0.00%)  0 1/224 (0.45%)  1
White blood cell count increased  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  10/234 (4.27%)  10 1/224 (0.45%)  1
Dehydration  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Periarthritis calcarea  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Type 2 diabetes mellitus  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  7/234 (2.99%)  7 6/224 (2.68%)  8
Arthritis  1  2/234 (0.85%)  2 0/224 (0.00%)  0
Back pain  1  4/234 (1.71%)  4 2/224 (0.89%)  3
Cartilage hypertrophy  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Chondrocalcinosis pyrophosphate  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Fasciitis  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Infrapatellar fat pad inflammation  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Jaw cyst  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Mixed connective tissue disease  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Muscle spasms  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Musculoskeletal pain  1  0/234 (0.00%)  0 3/224 (1.34%)  3
Musculoskeletal stiffness  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Myalgia  1  0/234 (0.00%)  0 3/224 (1.34%)  3
Neck pain  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Osteoarthritis  1  3/234 (1.28%)  3 8/224 (3.57%)  8
Pain in extremity  1  0/234 (0.00%)  0 4/224 (1.79%)  4
Periarthritis  1  3/234 (1.28%)  3 6/224 (2.68%)  9
Plantar fasciitis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Spinal osteoarthritis  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Tendonitis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Tenosynovitis  1  0/234 (0.00%)  0 5/224 (2.23%)  5
Tenosynovitis stenosans  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Trigger finger  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Nervous system disorders     
Carpal tunnel syndrome  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Cervicobrachial syndrome  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Dizziness  1  15/234 (6.41%)  16 2/224 (0.89%)  2
Dizziness postural  1  4/234 (1.71%)  4 0/224 (0.00%)  0
Dysarthria  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Dysgeusia  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Headache  1  9/234 (3.85%)  9 3/224 (1.34%)  3
Hypoaesthesia  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Migraine  1  2/234 (0.85%)  2 1/224 (0.45%)  1
Piriformis syndrome  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Sciatica  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Somnolence  1  45/234 (19.23%)  45 16/224 (7.14%)  17
Tension headache  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Tremor  1  4/234 (1.71%)  4 0/224 (0.00%)  0
Psychiatric disorders     
Anxiety  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Dysphoria  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Sleep talking  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Renal and urinary disorders     
Chromaturia  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Dysuria  1  5/234 (2.14%)  5 0/224 (0.00%)  0
Haematuria  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Hypertonic bladder  1  1/234 (0.43%)  1 1/224 (0.45%)  1
Pollakiuria  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Urinary retention  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Urine flow decreased  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Reproductive system and breast disorders     
Atrophic vulvovaginitis  1  1/118 (0.85%)  1 0/121 (0.00%)  0
Benign prostatic hyperplasia  1  1/116 (0.86%)  1 0/103 (0.00%)  0
Dysmenorrhoea  1  1/118 (0.85%)  1 1/121 (0.83%)  2
Menstruation irregular  1  0/118 (0.00%)  0 1/121 (0.83%)  1
Sexual dysfunction  1  2/234 (0.85%)  2 0/224 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Allergic pharyngitis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Asthma  1  1/234 (0.43%)  1 2/224 (0.89%)  2
Cough  1  3/234 (1.28%)  4 1/224 (0.45%)  1
Epistaxis  1  0/234 (0.00%)  0 1/224 (0.45%)  2
Hyperventilation  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Oropharyngeal pain  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Rhinitis allergic  1  2/234 (0.85%)  2 1/224 (0.45%)  1
Upper respiratory tract inflammation  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Skin and subcutaneous tissue disorders     
Asteatosis  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Dermatitis contact  1  0/234 (0.00%)  0 2/224 (0.89%)  2
Dry skin  1  0/234 (0.00%)  0 2/224 (0.89%)  2
Eczema  1  3/234 (1.28%)  4 3/224 (1.34%)  3
Eczema asteatotic  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Erythema  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Hyperhidrosis  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Pruritus  1  3/234 (1.28%)  3 1/224 (0.45%)  1
Rash  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Rash macular  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Skin erosion  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Swelling face  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Urticaria  1  0/234 (0.00%)  0 3/224 (1.34%)  3
Vascular disorders     
Hot flush  1  1/234 (0.43%)  1 0/224 (0.00%)  0
Peripheral arterial occlusive disease  1  0/234 (0.00%)  0 1/224 (0.45%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01855919     History of Changes
Other Study ID Numbers: 14376
F1J-JE-HMGY ( Other Identifier: Eli Lilly and Company )
First Submitted: May 14, 2013
First Posted: May 17, 2013
Results First Submitted: June 26, 2015
Results First Posted: July 23, 2015
Last Update Posted: July 23, 2015