ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 7 of 39 for:    LY2189265

A Study of LY2189265 in Japanese Participants With Type 2 Diabetes Mellitus

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: NCT01558271
Recruitment Status : Completed
First Posted : March 20, 2012
Results First Posted : October 30, 2014
Last Update Posted : May 22, 2015
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Type 2 Diabetes Mellitus
Interventions Drug: LY2189265
Drug: Placebo
Drug: Liraglutide
Enrollment 492
Recruitment Details  
Pre-assignment Details  
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description Once-weekly subcutaneous (SC) injection of 0.75 milligrams (mg) of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy. Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy. Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Period Title: Overall Study
Started 281 70 141
Received at Least 1 Dose of Study Drug 280 70 137
Completed 26 Weeks 271 63 128
Completed 263 59 124
Not Completed 18 11 17
Reason Not Completed
Adverse Event             6             3             4
Lost to Follow-up             1             0             0
Protocol Violation             1             0             0
Withdrawal by Subject             10             6             12
Physician Decision             0             2             1
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide Total
Hide Arm/Group Description Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy. Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy. Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy. Total of all reporting groups
Overall Number of Baseline Participants 280 70 137 487
Hide Baseline Analysis Population Description
Participants who received at least 1 dose of study medication.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 280 participants 70 participants 137 participants 487 participants
57.15  (9.57) 57.66  (8.34) 57.91  (10.93) 57.44  (9.63)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 280 participants 70 participants 137 participants 487 participants
Female
52
  18.6%
15
  21.4%
24
  17.5%
91
  18.7%
Male
228
  81.4%
55
  78.6%
113
  82.5%
396
  81.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Asian Number Analyzed 280 participants 70 participants 137 participants 487 participants
280 70 137 487
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 280 participants 70 participants 137 participants 487 participants
280 70 137 487
1.Primary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 26 Weeks
Hide Description Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) analysis with treatment, visit, treatment-by-visit, prestudy therapy (oral antihyperglycemic medication [OAM] yes/no), baseline body mass index (BMI) group (<25 or >=25 kilograms per meter squared [kg/m^2]) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect.
Time Frame Baseline, 26 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication with evaluable HbA1c data. Only pre-rescue measurements were used.
Arm/Group Title LY2189265 Placebo Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 24 weeks of open therapy.
Overall Number of Participants Analyzed 280 68 136
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-1.43  (0.05) 0.14  (0.10) -1.33  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo
Comments Approximately 490 participants were to be randomized in a 4:1:2 ratio to LY2189265, placebo, or Liraglutide, respectively. This sample size would provide greater than 99% power to demonstrate superiority of LY2189265 to placebo. This computation assumed a true mean difference in HbA1c change from baseline between LY2189265 and placebo being 0.8%, a common standard deviation of 1.1%, a 1-sided significance level of 0.025, and a 9% drop-out rate between randomization and Week 26.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.57
Confidence Interval (2-Sided) 95%
-1.79 to -1.35
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments Approximately 490 participants were to be randomized in a 4:1:2 ratio to LY2189265, placebo, or Liraglutide, respectively. This sample size would provide >90% power to confirm non-inferiority of LY2189265 to liraglutide by a margin of 0.4%. This computation assumed a true mean difference in HbA1c change from baseline between LY2189265 and Liraglutide being 0%, a common standard deviation of 1.1%, a 1-sided significance level of 0.025, and a 9% drop-out rate between randomization and Week 26.
Type of Statistical Test Non-Inferiority or Equivalence
Comments If the upper limit of the 95% Confidence Interval (CI) was <0.4%, then LY2189265 was declared non-inferior to Liraglutide. If the upper limit of the 95% CI was <0.0%, then LY2189265 was declared superior to liraglutide.
Statistical Test of Hypothesis P-Value 0.248
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.27 to 0.07
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 52 Weeks
Hide Description LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline HbA1c as a covariate, and participant as a random effect.
Time Frame Baseline, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication with evaluable HbA1c data. Only pre-rescue measurements were used.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 68 136
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HbA1c
-1.39  (0.06) -1.55  (0.12) -1.19  (0.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.39 to -0.01
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Who Achieved HbA1c <=6.5% or <7%
Hide Description The percentage of participants achieving HbA1c level less than 7.0% and less than or equal to 6.5% at Week 26 and Week 52 was analyzed with a Cochran-Mantel-Haenszel test stratified by prestudy therapy (OAM yes/no) and baseline BMI group (<25 or >=25 kg/m^2).
Time Frame Up to 26 and 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable HbA1c data. Only pre-rescue measurements were used. Missing endpoints were imputed with the last observation carried forward (LOCF), using only postbaseline data.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 68 136
Measure Type: Number
Unit of Measure: percentage of participants
HbA1c <7%, 26 weeks 71.4 5.9 69.1
HbA1c <=6.5%, 26 weeks 50.0 1.5 49.3
HbA1c <7%, 52 weeks 67.9 70.6 60.3
HbA1c <=6.5%, 52 weeks 49.3 52.9 41.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison for HbA1c <7% at 26 weeks between LY2189265 and placebo.
Method Cochran-Mantel-Haenszel
Comments Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.608
Comments Treatment comparison for HbA1c <7% at 26 weeks between LY2189265 and Liraglutide.
Method Cochran-Mantel-Haenszel
Comments Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison for HbA1c <=6.5% at 26 weeks between LY2189265 and placebo.
Method Cochran-Mantel-Haenszel
Comments Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.844
Comments Treatment comparison for HbA1c <=6.5% at 26 weeks between LY2189265 and Liraglutide.
Method Cochran-Mantel-Haenszel
Comments Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.112
Comments Treatment comparison for HbA1c <7% at 52 weeks between LY2189265 and Liraglutide.
Method Cochran-Mantel-Haenszel
Comments Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.103
Comments Treatment comparison for HbA1c <=6.5% at 52 weeks between LY2189265 and Liraglutide.
Method Cochran-Mantel-Haenszel
Comments Pairwise comparison was adjusted for prestudy therapy (OAM yes/no), baseline BMI group (<25 / >=25 kg/m^2), and baseline HbA1c group.
4.Secondary Outcome
Title Change From Baseline in Fasting Blood Glucose (FBG) at 26 Weeks and 52 Weeks
Hide Description LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline FBG as a covariate, and participant as a random effect.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable FBG data. Only pre-rescue measurements were used.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 276 62 134
Least Squares Mean (Standard Error)
Unit of Measure: milligrams per deciliter (mg/dL)
26 weeks -39.18  (1.60) 1.03  (3.30) -39.75  (2.27)
52 weeks -38.93  (1.72) -40.93  (3.62) -37.15  (2.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison for FBG at 26 weeks between LY2189265 and placebo.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -40.21
Confidence Interval (2-Sided) 95%
-47.31 to -33.11
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.835
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment comparison for FBG at 26 weeks between LY2189265 and Liraglutide.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
-4.82 to 5.96
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.553
Comments Treatment comparison for FBG at 52 weeks between LY2189265 and Liraglutide.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.77
Confidence Interval (2-Sided) 95%
-7.65 to 4.10
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) at 26 Weeks and 52 Weeks
Hide Description Participants were to test and record SMBG concentrations in their study diaries before each meal (breakfast, lunch, and dinner), approximately 2 hours after the start of each meal, and at bedtime. LS means were calculated using analysis of covariance (ANCOVA) model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline SMBG as a covariate.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication with evaluable SMBG data. Only pre-rescue measurements were used. Missing endpoints were imputed with the LOCF method, using only postbaseline data.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 277 69 133
Least Squares Mean (Standard Error)
Unit of Measure: milligrams per deciliter (mg/dL)
Pre-morning meal, 26 weeks -39.65  (1.55) -0.15  (3.04) -34.93  (2.19)
2 hours post-morning meal, 26 weeks -69.64  (2.80) -9.29  (5.48) -61.67  (3.96)
Pre-midday meal, 26 weeks -48.47  (2.05) 3.91  (4.03) -45.08  (2.91)
2 hours post-midday meal, 26 weeks -67.57  (2.94) -1.50  (5.77) -66.71  (4.16)
Pre-evening meal, 26 weeks -39.64  (2.15) 9.25  (4.22) -36.62  (3.05)
2 hours post-evening meal -56.70  (2.83) 0.93  (5.56) -53.14  (4.01)
Bedtime, 26 weeks -53.39  (2.81) 4.26  (5.51) -51.07  (3.94)
Pre-morning meal, 52 weeks -37.46  (1.58) -30.12  (3.10) -33.41  (2.23)
2 hours post-morning meal, 52 weeks -66.96  (2.87) -65.91  (5.62) -60.69  (4.06)
Pre-midday meal, 52 weeks -47.03  (1.86) -45.15  (3.64) -46.25  (2.63)
2 hours post-midday meal, 52 weeks -68.21  (2.74) -58.52  (5.38) -62.57  (3.88)
Pre-evening meal, 52 weeks -41.04  (1.08) -36.13  (3.70) -32.86  (2.67)
2 hours post-evening meal, 52 weeks -55.01  (2.58) -55.26  (5.06) -42.30  (3.65)
Bedtime, 52 weeks -55.76  (2.39) -51.19  (4.69) -49.10  (3.35)
6.Secondary Outcome
Title Change From Baseline in Body Weight at 26 Weeks and 52 Weeks
Hide Description LS means were calculated using MMRM analysis with treatment, visit, treatment-by-visit, prestudy therapy (OAM yes/no), baseline BMI group (<25 or >=25 kg/m^2) as fixed effects, baseline body weight as a covariate, and participant as a random effect.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication with evaluable body weight data. Only pre-rescue measurements were used.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 70 136
Least Squares Mean (Standard Error)
Unit of Measure: kilograms (kg)
26 weeks -0.02  (0.14) -0.63  (0.29) -0.36  (0.20)
52 weeks -0.17  (0.18) -1.03  (0.37) -0.13  (0.26)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment comparison for body weight at 26 weeks between LY2189265 and placebo.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
-0.02 to 1.23
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.168
Comments Treatment comparison for body weight at 26 weeks between LY2189265 and Liraglutide.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
-0.14 to 0.82
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.911
Comments Treatment comparison for body weight at 52 weeks between LY2189265 and Liraglutide.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.64 to 0.57
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Insulin Sensitivity Using Updated Homeostasis Model Assessment (HOMA 2) at 26 Weeks and 52 Weeks
Hide Description HOMA 2 quantifies insulin resistance and beta-cell function. HOMA2-S is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. Change in insulin sensitivity was assessed based on change from baseline of HOMA2-%S using fasting insulin (FI) and fasting C-peptide (FCP). LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline HOMA2-%S as a covariate.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable HOMA2-%S data. Only pre-rescue measurements were used. Missing endpoints were imputed with the LOCF method, using only postbaseline data.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 275 62 131
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HOMA2
HOMA2-%S based on FI, 26 weeks (n=254, 57, 115) -4.83  (2.34) -2.97  (4.83) -4.82  (3.43)
HOMA2-%S based on FCP, 26 weeks (n=275, 62, 131) -5.48  (1.93) -6.32  (3.99) -2.46  (2.75)
HOMA2-%S based on FI, 52 weeks (n=260, 60, 120) -7.75  (2.34) NA [1]   (NA) -5.26  (3.38)
HOMA2-%S based on FCP, 52 weeks (n=275, 62, 131) -11.72  (1.88) NA [1]   (NA) -10.68  (2.68)
[1]
For ANCOVA analyses at 52 weeks, LS Means were not calculated for the Placebo/LY2189265 group as the purpose of the Week 52 analysis was to evaluate the efficacy and safety of LY2189265 compared with Liraglutide treatment for a full 52 weeks.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.723
Comments Treatment comparison for HOMA2-%S based on fasting insulin at 26 weeks between LY2189265 and placebo.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.86
Confidence Interval (2-Sided) 95%
-12.20 to 8.48
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.998
Comments Treatment comparison for HOMA2-%S based on fasting insulin at 26 weeks between LY2189265 and Liraglutide.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-7.92 to 7.91
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.848
Comments Treatment comparison for HOMA2-%S based on fasting C-peptide at 26 weeks between LY2189265 and placebo.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
-7.72 to 9.38
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.357
Comments Treatment comparison for HOMA2-%S based on fasting C-peptide at 26 weeks between LY2189265 and Liraglutide.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.03
Confidence Interval (2-Sided) 95%
-9.48 to 3.42
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.533
Comments Treatment comparison for HOMA2-%S based on fasting insulin at 52 weeks between LY2189265 and Liraglutide.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -2.49
Confidence Interval (2-Sided) 95%
-10.35 to 5.36
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.747
Comments Treatment comparison for HOMA2-%S based on fasting C-peptide at 52 weeks between LY2189265 and Liraglutide.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.03
Confidence Interval (2-Sided) 95%
-7.32 to 5.25
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Beta-cell Function Using Updated Homeostasis Model Assessment (HOMA 2) at 26 Weeks and 52 Weeks
Hide Description HOMA 2 quantifies insulin resistance and beta-cell function. HOMA2-B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state beta-cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. Change in beta-cell function was assessed based on change from baseline of HOMA2-%B using fasting insulin (FI) and fasting C-peptide (FCP). LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline HOMA2-%B as a covariate.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable HOMA2-%B data. Only pre-rescue measurements were used. Missing endpoints were imputed with the LOCF method, using only postbaseline data.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 275 62 131
Least Squares Mean (Standard Error)
Unit of Measure: percentage of HOMA2
HHOMA2-%B based on FI, 26 weeks (n=254, 57, 115) 28.42  (1.54) 0.08  (3.14) 25.35  (2.23)
HOMA2-%B based on FCP, 26 weeks (n=275, 62, 131) 27.77  (1.27) 2.94  (2.61) 25.86  (1.79)
HOMA2-%B based on FI, 52 weeks (n=260, 60, 120) 27.81  (1.39) NA [1]   (NA) 25.89  (1.99)
HOMA2-%B based on FCP, 52 weeks (n=275, 62, 131) 29.59  (1.37) NA [1]   (NA) 28.85  (1.93)
[1]
For ANCOVA analyses at 52 weeks, LS Means were not calculated for the Placebo/LY2189265 group as the purpose of the Week 52 analysis was to evaluate the efficacy and safety of LY2189265 compared with Liraglutide treatment for a full 52 weeks.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison for HOMA2-%B based on fasting insulin at 26 weeks between LY2189265 and placebo.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 28.35
Confidence Interval (2-Sided) 95%
21.63 to 35.07
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.242
Comments Treatment comparison for HOMA2-%B based on fasting insulin at 26 weeks between LY2189265 and Liraglutide.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.08
Confidence Interval (2-Sided) 95%
-2.09 to 8.24
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Treatment comparison for HOMA2-%B based on fasting C-peptide at 26 weeks between LY2189265 and placebo.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 24.82
Confidence Interval (2-Sided) 95%
19.25 to 30.40
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.376
Comments Treatment comparison for HOMA2-%B based on fasting C-peptide at 26 weeks between LY2189265 and Liraglutide.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
-2.32 to 6.13
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.417
Comments Treatment comparison for HOMA2-%B based on fasting insulin at 52 weeks between LY2189265 and Liraglutide.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
-2.72 to 6.54
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.753
Comments Treatment comparison for HOMA2-%B based on fasting C-peptide at 52 weeks between LY2189265 and Liraglutide.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
-3.83 to 5.29
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With Hypoglycemic Episodes
Hide Description The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least one hypoglycemic episode over the 26-week or 52-week treatment period by the total number of participants analyzed, multiplied by 100%. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline through 26 weeks and Baseline through 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 70 137
Measure Type: Number
Unit of Measure: percentage of participants
26 weeks 2.1 1.4 1.5
52 weeks 2.9 2.9 2.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LY2189265, Placebo/LY2189265
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Treatment comparison at 26 weeks between LY2189265 and placebo.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Treatment comparison at 26 weeks between LY2189265 and Liraglutide.
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection LY2189265, Liraglutide
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.999
Comments Treatment comparison at 52 weeks between LY2189265 and Liraglutide.
Method Fisher Exact
Comments [Not Specified]
10.Secondary Outcome
Title 30-Day Rate of Hypoglycemic Episodes
Hide Description The 30-day total hypoglycemia rate over 26 weeks and 52 weeks of treatment is summarized. All classifications of hypoglycemia (documented symptomatic, asymptomatic, severe, nocturnal, non-nocturnal, probable symptomatic, relative, and unspecified) were included, except for episodes of relative hypoglycemia that were not severe. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline through 26 weeks and Baseline through 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication. One participant in the Liraglutide reporting group received study drug but discontinued from the study on the same day and, therefore, was not included in the analysis.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 70 136
Mean (Standard Deviation)
Unit of Measure: events per participant per 30 days
26 weeks 0.01  (0.04) 0.00  (0.02) 0.00  (0.02)
52 weeks 0.00  (0.02) 0.01  (0.09) 0.01  (0.04)
11.Secondary Outcome
Title Number of Participants With Adjudicated Cardiovascular Events at 26 Weeks and 52 Weeks
Hide Description Deaths and nonfatal cardiovascular adverse events were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal cardiovascular events subjected to adjudication included myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline through 26 weeks and Baseline through 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 70 137
Measure Type: Number
Unit of Measure: participants
26 weeks 0 0 0
52 weeks 0 0 0
12.Secondary Outcome
Title Change From Baseline in Pulse Rate at 26 Weeks and 52 Weeks
Hide Description Sitting pulse rate was measured. LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline pulse rate as a covariate.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable pulse rate data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 70 136
Least Squares Mean (Standard Error)
Unit of Measure: beats per minute (bpm)
26 weeks 3.35  (0.45) 1.49  (0.90) 4.77  (0.64)
52 weeks 3.11  (0.42) 4.42  (0.86) 5.13  (0.60)
13.Secondary Outcome
Title Change From Baseline in Blood Pressure at 26 Weeks and 52 Weeks
Hide Description Sitting systolic blood pressure (SBP) and sitting diastolic blood pressure (DBP) were measured. LS means were calculated using ANCOVA model with treatment, prestudy therapy (OAM yes/no), and baseline BMI group (<25 or >=25 kg/m^2) as fixed effects and baseline blood pressure as a covariate.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable blood pressure data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 70 136
Least Squares Mean (Standard Error)
Unit of Measure: milliliters of mercury (mmHG)
SBP, 26 weeks 0.62  (0.62) 0.53  (1.25) -2.10  (0.89)
DBP, 26 weeks 1.09  (0.39) 0.29  (0.78) 0.43  (0.56)
SBP, 52 weeks 1.32  (0.66) 0.37  (1.37) -1.86  (0.95)
DBP, 52 weeks 1.41  (0.41) 1.16  (0.86) 1.17  (0.60)
14.Secondary Outcome
Title Number of Participants With Adjudicated Pancreatitis at 26 Weeks and 52 Weeks
Hide Description Events of pancreatitis (including suspected pancreatitis and severe or serious abdominal pain) were adjudicated by a committee of expert physicians external to the Sponsor. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame Baseline through 26 weeks and Baseline through 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 70 137
Measure Type: Number
Unit of Measure: participants
26 weeks 0 0 0
52 weeks 0 0 0
15.Secondary Outcome
Title Change From Baseline in Pancreatic Enzymes at 26 Weeks and 52 Weeks
Hide Description Pancreatic enzyme (lipase and total amylase) concentrations were measured.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable pancreatic enzyme data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 275 65 131
Median (Inter-Quartile Range)
Unit of Measure: units/liter
Lipase, 26 weeks
7.0
(1.0 to 13.0)
1.0
(-6.0 to 5.0)
11.0
(5.0 to 21.0)
Total Amylase, 26 weeks
7.0
(2.0 to 15.0)
0.0
(-6.0 to 6.0)
7.0
(1.0 to 15.0)
Lipase, 52 weeks
6.0
(1.0 to 12.0)
6.0
(2.0 to 12.0)
9.0
(3.0 to 19.0)
Total Amylase, 52 weeks
7.0
(1.0 to 14.0)
9.0
(3.0 to 14.0)
6.0
(1.0 to 11.0)
16.Secondary Outcome
Title Change From Baseline in Serum Calcitonin at 26 Weeks and 52 Weeks
Hide Description [Not Specified]
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable serum calcitonin data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 274 65 131
Median (Inter-Quartile Range)
Unit of Measure: picograms/milliliter
26 weeks
0.0
(0.0 to 0.0)
0.0
(0.0 to 0.0)
0.0
(0.0 to 0.0)
52 weeks
0.0
(0.0 to 0.0)
0.0
(0.0 to 0.0)
0.0
(0.0 to 0.0)
17.Secondary Outcome
Title Number of Participants With Treatment-Emergent LY2189265 Anti-Drug Antibodies (ADAs) at 26 Weeks and 52 Weeks
Time Frame Baseline through 26 weeks and Baseline through 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication and had LY2189265 evaluable ADA data.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 279 68 134
Measure Type: Number
Unit of Measure: participants
26 weeks (n=279, 68, 133) 3 0 0
52 weeks (n=279, 68, 134) 3 0 0
18.Secondary Outcome
Title Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26 Weeks and 52 Weeks
Hide Description Additional intervention was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. The number of participants requiring additional intervention due to hyperglycemia is summarized cumulatively at 26 and 52 weeks.
Time Frame Baseline through 26 weeks and Baseline through 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of study medication.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 280 70 137
Measure Type: Number
Unit of Measure: participants
26 weeks 0 0 0
52 weeks 0 0 0
19.Secondary Outcome
Title Change From Baseline in Electrocardiogram Parameters at 26 Weeks and 52 Weeks
Hide Description Fridericia Corrected QT (QTcF) Interval and PR Interval are summarized. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave and was calculated from electrocardiogram (ECG) data using Fridericia's formula: QTcF = QT/RR^0.33. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. PR is the interval between the P wave and the QRS complex. LS means were calculated using ANCOVA model with treatment as a fixed effect and the baseline ECG parameter as the covariate.
Time Frame Baseline, 26 weeks, 52 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants who were randomized and received at least one dose of study medication with evaluable ECG data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description:
Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy.
Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
Overall Number of Participants Analyzed 274 65 128
Least Squares Mean (Standard Error)
Unit of Measure: milliseconds (msec)
QTcF, 26 weeks (n=273, 64, 128) -2.02  (0.70) -0.96  (1.44) -1.89  (1.02)
QTcF, 52 weeks (n=274, 64, 128) -2.76  (0.68) -0.80  (1.41) -4.35  (1.00)
PR, 26 weeks (n=269, 65, 126) 2.20  (0.60) -0.45  (1.22) 2.07  (0.88)
PR, 52 weeks (n=270, 65, 126) 2.81  (0.82) 2.60  (1.33) 3.71  (1.03)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LY2189265 Placebo/LY2189265 Liraglutide
Hide Arm/Group Description Once-weekly SC injection of 0.75 mg of LY2189265 for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy. Once-weekly SC injection of placebo for 26 weeks of blinded therapy, followed by once-weekly SC injection of 0.75 mg LY2189265 for an additional 26 weeks of open therapy. Once-daily SC injection of 0.3 mg of Liraglutide for the first week, followed by 0.6 mg of Liraglutide for the second week, and then 0.9 mg of Liraglutide for the remaining 50 weeks of open therapy.
All-Cause Mortality
LY2189265 Placebo/LY2189265 Liraglutide
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
LY2189265 Placebo/LY2189265 Liraglutide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/280 (3.21%)      5/70 (7.14%)      7/137 (5.11%)    
Blood and lymphatic system disorders       
Eosinophilia  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Ear and labyrinth disorders       
Sudden hearing loss  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Gastrointestinal disorders       
Large intestine polyp  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Hepatobiliary disorders       
Bile duct stone  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Infections and infestations       
Bacterial infection  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Gastroenteritis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Hiv infection  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Pneumocystis jirovecii pneumonia  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Wound infection  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Injury, poisoning and procedural complications       
Femoral neck fracture  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Hand fracture  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Intervertebral disc protrusion  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Lumbar spinal stenosis  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Rotator cuff syndrome  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Colon cancer  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Invasive ductal breast carcinoma  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Lung adenocarcinoma  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Ovarian cancer  1  0/52 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Pancreatic carcinoma  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Prostate cancer  1  0/228 (0.00%)  0 1/55 (1.82%)  1 0/113 (0.00%)  0
Nervous system disorders       
Intracranial aneurysm  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
LY2189265 Placebo/LY2189265 Liraglutide
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   182/280 (65.00%)      53/70 (75.71%)      94/137 (68.61%)    
Blood and lymphatic system disorders       
Anaemia  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Anaemia macrocytic  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Cardiac disorders       
Palpitations  1  5/280 (1.79%)  5 0/70 (0.00%)  0 0/137 (0.00%)  0
Ventricular extrasystoles  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Ear and labyrinth disorders       
Deafness neurosensory  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Ear pain  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Eustachian tube obstruction  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Vertigo  1  2/280 (0.71%)  2 1/70 (1.43%)  1 1/137 (0.73%)  1
Endocrine disorders       
Goitre  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Hyperthyroidism  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Eye disorders       
Asthenopia  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Cataract  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Conjunctivitis allergic  1  0/280 (0.00%)  0 1/70 (1.43%)  2 1/137 (0.73%)  1
Diabetic retinopathy  1  2/280 (0.71%)  2 1/70 (1.43%)  1 2/137 (1.46%)  2
Dry eye  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Eyelid oedema  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Glaucoma  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Iritis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Keratitis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Macular oedema  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Pingueculitis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Retinal tear  1  1/280 (0.36%)  1 1/70 (1.43%)  1 1/137 (0.73%)  1
Vitreous floaters  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Vitreous haemorrhage  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Gastrointestinal disorders       
Abdominal discomfort  1  9/280 (3.21%)  10 1/70 (1.43%)  1 5/137 (3.65%)  5
Abdominal distension  1  12/280 (4.29%)  12 0/70 (0.00%)  0 7/137 (5.11%)  7
Abdominal pain  1  3/280 (1.07%)  3 2/70 (2.86%)  2 1/137 (0.73%)  1
Abdominal pain upper  1  4/280 (1.43%)  4 2/70 (2.86%)  2 3/137 (2.19%)  3
Abnormal faeces  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Anal fistula  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Constipation  1  22/280 (7.86%)  24 4/70 (5.71%)  4 11/137 (8.03%)  11
Dental caries  1  4/280 (1.43%)  5 3/70 (4.29%)  3 4/137 (2.92%)  4
Diarrhoea  1  20/280 (7.14%)  23 6/70 (8.57%)  6 6/137 (4.38%)  6
Diverticulum intestinal  1  0/280 (0.00%)  0 1/70 (1.43%)  1 1/137 (0.73%)  1
Dry mouth  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Dyschezia  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Dyspepsia  1  4/280 (1.43%)  5 1/70 (1.43%)  1 3/137 (2.19%)  3
Dysphagia  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Epigastric discomfort  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Eructation  1  2/280 (0.71%)  3 0/70 (0.00%)  0 0/137 (0.00%)  0
Flatulence  1  2/280 (0.71%)  2 0/70 (0.00%)  0 2/137 (1.46%)  2
Gastric disorder  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Gastric polyps  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Gastric ulcer  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Gastritis  1  2/280 (0.71%)  3 1/70 (1.43%)  1 3/137 (2.19%)  5
Gastritis atrophic  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Gastritis erosive  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Gastroduodenal ulcer  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Gastrooesophageal reflux disease  1  2/280 (0.71%)  2 1/70 (1.43%)  1 4/137 (2.92%)  4
Haemorrhoids  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Hiatus hernia  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Hyperchlorhydria  1  1/280 (0.36%)  3 0/70 (0.00%)  0 0/137 (0.00%)  0
Large intestine polyp  1  3/280 (1.07%)  3 0/70 (0.00%)  0 4/137 (2.92%)  4
Nausea  1  17/280 (6.07%)  25 2/70 (2.86%)  2 11/137 (8.03%)  18
Periodontal disease  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Radicular cyst  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Stomatitis  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Vomiting  1  5/280 (1.79%)  6 0/70 (0.00%)  0 1/137 (0.73%)  2
General disorders       
Application site haematoma  1  1/280 (0.36%)  1 0/70 (0.00%)  0 2/137 (1.46%)  2
Chest pain  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Device failure  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Early satiety  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Fatigue  1  1/280 (0.36%)  1 0/70 (0.00%)  0 3/137 (2.19%)  3
Feeling abnormal  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Induration  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Injection site bruising  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Injection site dermatitis  1  1/280 (0.36%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Injection site erythema  1  1/280 (0.36%)  1 0/70 (0.00%)  0 4/137 (2.92%)  5
Injection site haemorrhage  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Injection site induration  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Injection site pain  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Injection site pruritus  1  5/280 (1.79%)  5 0/70 (0.00%)  0 5/137 (3.65%)  6
Injection site rash  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Injection site reaction  1  3/280 (1.07%)  3 1/70 (1.43%)  1 0/137 (0.00%)  0
Injection site swelling  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Local swelling  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Malaise  1  2/280 (0.71%)  8 1/70 (1.43%)  1 1/137 (0.73%)  1
Oedema peripheral  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Pyrexia  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Thirst  1  0/280 (0.00%)  0 1/70 (1.43%)  1 1/137 (0.73%)  1
Xerosis  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Hepatobiliary disorders       
Alcoholic liver disease  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Cholelithiasis  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Gallbladder polyp  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Hepatic cyst  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Hepatic function abnormal  1  1/280 (0.36%)  1 1/70 (1.43%)  1 1/137 (0.73%)  1
Hepatic steatosis  1  5/280 (1.79%)  5 0/70 (0.00%)  0 2/137 (1.46%)  2
Hyperplastic cholecystopathy  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Liver injury  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Immune system disorders       
Seasonal allergy  1  2/280 (0.71%)  2 0/70 (0.00%)  0 1/137 (0.73%)  1
Infections and infestations       
Acute sinusitis  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Anisakiasis  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Body tinea  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Bronchitis  1  7/280 (2.50%)  9 2/70 (2.86%)  2 3/137 (2.19%)  4
Bronchitis viral  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Candida infection  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Chronic sinusitis  1  1/280 (0.36%)  1 1/70 (1.43%)  1 1/137 (0.73%)  1
Conjunctivitis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Cystitis  1  2/280 (0.71%)  3 1/70 (1.43%)  1 1/137 (0.73%)  1
Dermatitis infected  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Enteritis infectious  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Fungal skin infection  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Gastroenteritis  1  7/280 (2.50%)  7 0/70 (0.00%)  0 1/137 (0.73%)  1
Gastroenteritis viral  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Gingivitis  1  3/280 (1.07%)  3 0/70 (0.00%)  0 1/137 (0.73%)  1
Helicobacter gastritis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Helicobacter infection  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Herpes virus infection  1  0/280 (0.00%)  0 1/70 (1.43%)  1 1/137 (0.73%)  1
Herpes zoster  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Hordeolum  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Influenza  1  1/280 (0.36%)  1 3/70 (4.29%)  3 2/137 (1.46%)  2
Intervertebral discitis  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Nasopharyngitis  1  52/280 (18.57%)  61 7/70 (10.00%)  12 24/137 (17.52%)  34
Oral herpes  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Otitis externa  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Otitis media  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Parotitis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Periodontitis  1  1/280 (0.36%)  1 1/70 (1.43%)  1 1/137 (0.73%)  2
Pharyngitis  1  3/280 (1.07%)  3 3/70 (4.29%)  4 3/137 (2.19%)  3
Pharyngitis bacterial  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Pyoderma  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Rhinitis  1  3/280 (1.07%)  3 0/70 (0.00%)  0 0/137 (0.00%)  0
Sialoadenitis  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Sinusitis  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Tinea infection  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Tinea pedis  1  1/280 (0.36%)  1 1/70 (1.43%)  1 2/137 (1.46%)  2
Tooth abscess  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Upper respiratory tract infection  1  1/280 (0.36%)  2 1/70 (1.43%)  1 1/137 (0.73%)  1
Injury, poisoning and procedural complications       
Arthropod bite  1  0/280 (0.00%)  0 1/70 (1.43%)  1 1/137 (0.73%)  3
Arthropod sting  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Chillblains  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Contusion  1  4/280 (1.43%)  4 0/70 (0.00%)  0 5/137 (3.65%)  5
Epicondylitis  1  0/280 (0.00%)  0 2/70 (2.86%)  2 1/137 (0.73%)  1
Excoriation  1  3/280 (1.07%)  3 0/70 (0.00%)  0 0/137 (0.00%)  0
Fibula fracture  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Hand fracture  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Laceration  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Ligament sprain  1  2/280 (0.71%)  3 0/70 (0.00%)  0 1/137 (0.73%)  1
Limb crushing injury  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Limb injury  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Meniscus injury  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Muscle strain  1  1/280 (0.36%)  1 0/70 (0.00%)  0 2/137 (1.46%)  2
Post-traumatic neck syndrome  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Rib fracture  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Road traffic accident  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Scratch  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Stress fracture  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Subdural haematoma  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Sunburn  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Thermal burn  1  1/280 (0.36%)  1 2/70 (2.86%)  2 1/137 (0.73%)  1
Investigations       
Alanine aminotransferase increased  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Amylase increased  1  3/280 (1.07%)  3 0/70 (0.00%)  0 1/137 (0.73%)  1
Arteriogram coronary  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Aspartate aminotransferase increased  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Blood creatine phosphokinase increased  1  3/280 (1.07%)  3 0/70 (0.00%)  0 3/137 (2.19%)  4
Blood triglycerides increased  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Blood uric acid increased  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Blood urine present  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Crystal urine present  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Electrocardiogram t wave abnormal  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Gamma-glutamyltransferase increased  1  2/280 (0.71%)  2 0/70 (0.00%)  0 1/137 (0.73%)  1
Lipase increased  1  10/280 (3.57%)  11 2/70 (2.86%)  2 3/137 (2.19%)  3
Liver function test abnormal  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Monocyte count increased  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Occult blood positive  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Pancreatic enzymes increased  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Prostatic specific antigen increased  1  0/228 (0.00%)  0 1/55 (1.82%)  1 0/113 (0.00%)  0
Skin test positive  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Transaminases increased  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Urine albumin/creatinine ratio increased  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
White blood cell count decreased  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Metabolism and nutrition disorders       
Decreased appetite  1  2/280 (0.71%)  2 2/70 (2.86%)  2 8/137 (5.84%)  8
Dyslipidaemia  1  1/280 (0.36%)  1 0/70 (0.00%)  0 2/137 (1.46%)  2
Gout  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Hyperamylasaemia  1  0/280 (0.00%)  0 1/70 (1.43%)  2 0/137 (0.00%)  0
Hyperglycaemia  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Hyperlipidaemia  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Hyperuricaemia  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  4/280 (1.43%)  4 0/70 (0.00%)  0 1/137 (0.73%)  1
Arthritis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Back pain  1  8/280 (2.86%)  9 3/70 (4.29%)  3 6/137 (4.38%)  7
Cervical spinal stenosis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Flank pain  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Intervertebral disc protrusion  1  5/280 (1.79%)  5 0/70 (0.00%)  0 1/137 (0.73%)  1
Lumbar spinal stenosis  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Muscle fatigue  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Muscle spasms  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Muscular weakness  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Musculoskeletal pain  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Musculoskeletal stiffness  1  0/280 (0.00%)  0 1/70 (1.43%)  1 1/137 (0.73%)  1
Myalgia  1  1/280 (0.36%)  1 1/70 (1.43%)  1 3/137 (2.19%)  3
Myositis  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Osteitis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Osteoarthritis  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Osteoporosis  1  0/280 (0.00%)  0 1/70 (1.43%)  1 1/137 (0.73%)  1
Pain in extremity  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Periarthritis  1  3/280 (1.07%)  3 1/70 (1.43%)  1 1/137 (0.73%)  1
Spinal osteoarthritis  1  4/280 (1.43%)  4 1/70 (1.43%)  1 0/137 (0.00%)  0
Tendonitis  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Tenosynovitis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Trigger finger  1  1/280 (0.36%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Colon cancer  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Duodenal neoplasm  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Meningioma  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Skin papilloma  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Thyroid neoplasm  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Uterine leiomyoma  1  1/52 (1.92%)  1 1/15 (6.67%)  1 0/24 (0.00%)  0
Nervous system disorders       
Autonomic nervous system imbalance  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Autonomic neuropathy  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Carotid arteriosclerosis  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Cervical radiculopathy  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Cervicobrachial syndrome  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Diabetic neuropathy  1  1/280 (0.36%)  1 1/70 (1.43%)  1 2/137 (1.46%)  2
Dizziness  1  1/280 (0.36%)  1 3/70 (4.29%)  3 1/137 (0.73%)  1
Dizziness exertional  1  1/280 (0.36%)  4 0/70 (0.00%)  0 0/137 (0.00%)  0
Head discomfort  1  1/280 (0.36%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Headache  1  2/280 (0.71%)  2 2/70 (2.86%)  2 5/137 (3.65%)  5
Hypoaesthesia  1  2/280 (0.71%)  2 5/70 (7.14%)  5 1/137 (0.73%)  1
Intercostal neuralgia  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Lacunar infarction  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Paraesthesia  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Radial nerve palsy  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Sciatica  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Somnolence  1  2/280 (0.71%)  6 0/70 (0.00%)  0 2/137 (1.46%)  3
Psychiatric disorders       
Anxiety disorder  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Insomnia  1  1/280 (0.36%)  1 2/70 (2.86%)  2 1/137 (0.73%)  1
Irritability  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Sleep disorder  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Renal and urinary disorders       
Calculus ureteric  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Calculus urinary  1  0/280 (0.00%)  0 1/70 (1.43%)  1 1/137 (0.73%)  1
Cystitis noninfective  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Diabetic nephropathy  1  4/280 (1.43%)  4 1/70 (1.43%)  1 1/137 (0.73%)  1
Haematuria  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Hypertonic bladder  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Nephrolithiasis  1  0/280 (0.00%)  0 0/70 (0.00%)  0 2/137 (1.46%)  2
Renal cyst  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Reproductive system and breast disorders       
Benign prostatic hyperplasia  1  2/228 (0.88%)  2 0/55 (0.00%)  0 0/113 (0.00%)  0
Calculus prostatic  1  0/228 (0.00%)  0 0/55 (0.00%)  0 1/113 (0.88%)  1
Cystocele  1  0/52 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Erectile dysfunction  1  1/228 (0.44%)  1 0/55 (0.00%)  0 0/113 (0.00%)  0
Metrorrhagia  1  1/52 (1.92%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Prostatitis  1  1/228 (0.44%)  1 0/55 (0.00%)  0 0/113 (0.00%)  0
Prostatomegaly  1  0/228 (0.00%)  0 0/55 (0.00%)  0 1/113 (0.88%)  1
Rectocele  1  0/52 (0.00%)  0 1/15 (6.67%)  1 0/24 (0.00%)  0
Vulvovaginal pruritus  1  1/52 (1.92%)  1 0/15 (0.00%)  0 0/24 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Asthma  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Epistaxis  1  2/280 (0.71%)  2 0/70 (0.00%)  0 1/137 (0.73%)  1
Hiccups  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Hyperventilation  1  0/280 (0.00%)  0 1/70 (1.43%)  2 0/137 (0.00%)  0
Oropharyngeal discomfort  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Rhinitis allergic  1  2/280 (0.71%)  2 1/70 (1.43%)  1 4/137 (2.92%)  4
Rhinorrhoea  1  2/280 (0.71%)  3 0/70 (0.00%)  0 0/137 (0.00%)  0
Upper respiratory tract inflammation  1  4/280 (1.43%)  8 0/70 (0.00%)  0 3/137 (2.19%)  3
Vasomotor rhinitis  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Skin and subcutaneous tissue disorders       
Acne  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Alopecia areata  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  2
Dermal cyst  1  1/280 (0.36%)  1 1/70 (1.43%)  1 0/137 (0.00%)  0
Dermatitis  1  2/280 (0.71%)  2 0/70 (0.00%)  0 0/137 (0.00%)  0
Dermatitis contact  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Drug eruption  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Dry skin  1  1/280 (0.36%)  1 0/70 (0.00%)  0 1/137 (0.73%)  1
Eczema  1  4/280 (1.43%)  5 1/70 (1.43%)  1 0/137 (0.00%)  0
Haemorrhage subcutaneous  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Hyperhidrosis  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Hyperkeratosis  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Miliaria  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Pruritus  1  4/280 (1.43%)  4 2/70 (2.86%)  3 3/137 (2.19%)  3
Rash  1  1/280 (0.36%)  1 1/70 (1.43%)  1 2/137 (1.46%)  3
Skin exfoliation  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Skin mass  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Urticaria  1  0/280 (0.00%)  0 0/70 (0.00%)  0 3/137 (2.19%)  5
Social circumstances       
Denture wearer  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Surgical and medical procedures       
Dental care  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Dental prosthesis placement  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Intra-cerebral aneurysm operation  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Large intestinal polypectomy  1  3/280 (1.07%)  3 0/70 (0.00%)  0 0/137 (0.00%)  0
Limb operation  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Photocoagulation  1  0/280 (0.00%)  0 1/70 (1.43%)  1 0/137 (0.00%)  0
Retinal laser coagulation  1  1/280 (0.36%)  1 0/70 (0.00%)  0 0/137 (0.00%)  0
Tooth extraction  1  1/280 (0.36%)  1 0/70 (0.00%)  0 2/137 (1.46%)  3
Tooth repair  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Vascular disorders       
Hypertension  1  7/280 (2.50%)  7 2/70 (2.86%)  2 4/137 (2.92%)  4
Orthostatic hypotension  1  0/280 (0.00%)  0 0/70 (0.00%)  0 1/137 (0.73%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
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: NCT01558271     History of Changes
Other Study ID Numbers: 13990
H9X-JE-GBDP ( Other Identifier: Eli Lilly and Company )
First Submitted: March 12, 2012
First Posted: March 20, 2012
Results First Submitted: October 22, 2014
Results First Posted: October 30, 2014
Last Update Posted: May 22, 2015