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A Study of LY2189265 Compared to Sitagliptin in Participants With Type 2 Diabetes Mellitus on Metformin

This study has been completed.
Sponsor:
Collaborators:
United BioSource Corporation
Tessella Inc.
Berry Consultants
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00734474
First received: August 12, 2008
Last updated: March 31, 2015
Last verified: March 2015
Results First Received: October 3, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Diabetes Mellitus, Type 2
Interventions: Drug: LY2189265
Drug: Sitagliptin
Drug: Placebo solution
Drug: Placebo tablet
Drug: Metformin

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
3.0 mg LY2189265

LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)

2.0 mg LY2189265

LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)

1.5 mg LY2189265

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks

Placebo: tablet, administered orally, once daily for 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

1.0 mg LY2189265

LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)

0.75 mg LY2189265

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks

Placebo: tablet, administered orally, once daily for 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

0.5 mg LY2189265

LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)

0.25 mg LY2189265

LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)

Sitagliptin

Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks

Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

Placebo/Sitagliptin

Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks

Placebo: tablet, administered orally, once daily for 26 weeks

Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks


Participant Flow:   Overall Study
    3.0 mg LY2189265   2.0 mg LY2189265   1.5 mg LY2189265   1.0 mg LY2189265   0.75 mg LY2189265   0.5 mg LY2189265   0.25 mg LY2189265   Sitagliptin   Placebo/Sitagliptin
STARTED   15   30   304   10   302   25   24   315   177 
Received at Least 1 Dose of Study Drug   15   30   304   10   302   25   24   315   177 
Entered Study Before Dose Decision Point   15   30   25   10   21   25   24   42   38 
Completed Up to Dose Decision Point   8 [1]   25 [1]   24 [2]   8 [1]   21 [2]   21 [1]   23 [1]   42 [3]   34 [3] 
Entered Study After Dose Decision Point   0   0   279   0   281   0   0   273   139 
Completed 26-Week Visit   0   0   258   2   268   2   2   270   124 
Completed 52-Week Visit   0   0   238   0   243   0   0   238   112 
COMPLETED   0   0   192   0   184   0   0   186   95 
NOT COMPLETED   15   30   112   10   118   25   24   129   82 
Entry Criteria Not Met                0                0                5                0                3                1                0                1                1 
Lost to Follow-up                1                0                13                0                11                1                0                9                4 
Withdrawal by Subject                2                1                18                0                24                2                0                36                21 
Physician Decision                0                0                4                1                11                0                0                9                9 
Adverse Event                4                4                63                1                64                0                1                65                39 
Protocol Violation                0                0                4                0                3                0                0                3                1 
Sponsor Decision, Arm Discontinued                8                25                0                8                0                21                23                0                0 
Sponsor Decision                0                0                0                0                2                0                0                0                0 
Death                0                0                1                0                0                0                0                2                1 
Lack of Efficacy                0                0                4                0                0                0                0                4                6 
[1] These participants discontinued the study after the dose decision point.
[2] These participants continued the study after the dose decision point (selected arm).
[3] These participants continued the study after the dose decision point (comparator arm).



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All randomized participants.

Reporting Groups
  Description
3.0 mg LY2189265

LY2189265 (Dulaglutide): 3.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.1 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.1 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.1 weeks)

2.0 mg LY2189265

LY2189265 (Dulaglutide): 2.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 20.4 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 20.4 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 20.4 weeks)

1.5 mg LY2189265

LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks

Placebo: tablet, administered orally, once daily for 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

1.0 mg LY2189265

LY2189265 (Dulaglutide): 1.0 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)

0.75 mg LY2189265

LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC) injection, once weekly for 104 weeks

Placebo: tablet, administered orally, once daily for 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

0.5 mg LY2189265

LY2189265 (Dulaglutide): 0.5 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 27.4 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 27.4 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 27.4 weeks)

0.25 mg LY2189265

LY2189265 (Dulaglutide): 0.25 milligrams (mg), subcutaneous (SC) injection, once weekly up to decision point (maximum exposure duration of 24.4 weeks)

Placebo: tablet, administered orally, once daily up to decision point (maximum exposure duration of 24.4 weeks)

Metformin: at least 1500 milligrams per day (mg/day), administered orally up to decision point (maximum exposure duration of 24.4 weeks)

Sitagliptin

Sitagliptin: 100-milligrams (mg) tablet, administered orally, once daily for 104 weeks

Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

Placebo/Sitagliptin

Placebo: solution, subcutaneous (SC) injection, once weekly for 104 weeks

Placebo: tablet, administered orally, once daily for 26 weeks

Sitagliptin: after 26 weeks, 100-milligrams (mg) tablet, administered orally, once daily for 78 weeks

Metformin: at least 1500 milligrams per day (mg/day), administered orally for 104 weeks

Total Total of all reporting groups

Baseline Measures
   3.0 mg LY2189265   2.0 mg LY2189265   1.5 mg LY2189265   1.0 mg LY2189265   0.75 mg LY2189265   0.5 mg LY2189265   0.25 mg LY2189265   Sitagliptin   Placebo/Sitagliptin   Total 
Overall Participants Analyzed 
[Units: Participants]
 15   30   304   10   302   25   24   315   177   1202 
Age 
[Units: Years]
Mean (Standard Deviation)
 52.81  (10.66)   52.56  (10.95)   53.66  (10.02)   55.38  (8.71)   54.35  (9.81)   54.70  (9.72)   56.51  (6.56)   53.75  (10.27)   54.91  (9.05)   54.09  (9.85) 
Gender 
[Units: Participants]
                   
Female   10   22   158   7   168   12   15   164   87   643 
Male   5   8   146   3   134   13   9   151   90   559 
Race/Ethnicity, Customized 
[Units: Participants]
                   
Aboriginal and/or Torres Strait Islander   0   0   0   0   0   0   0   1   0   1 
African   1   3   16   0   12   2   0   7   9   50 
Caucasian   7   13   157   4   162   9   12   158   91   613 
East Asian   0   6   50   0   47   0   5   52   28   188 
Hispanic   7   8   54   6   51   14   6   67   38   251 
Native American   0   0   0   0   0   0   0   1   0   1 
West Asian (Indian sub-continent)   0   0   27   0   30   0   1   28   11   97 
Unknown or Not Reported   0   0   0   0   0   0   0   1   0   1 
Region of Enrollment 
[Units: Participants]
                   
United States   9   17   73   4   83   10   7   80   46   329 
Taiwan   0   1   19   0   18   0   3   20   12   73 
Spain   0   0   10   0   11   0   0   11   4   36 
Russian Federation   0   0   21   0   18   0   0   17   8   64 
India   0   0   27   0   29   0   0   28   12   96 
France   0   0   12   0   14   0   0   12   8   46 
Mexico   3   3   32   5   30   10   6   35   27   151 
Puerto Rico   1   2   12   0   5   3   0   10   7   40 
Canada   0   0   13   0   11   0   0   12   6   42 
Poland   1   0   20   0   23   2   2   23   12   83 
Romania   1   2   7   1   4   0   4   8   5   32 
Germany   0   0   31   0   31   0   0   28   15   105 
Korea, Republic of   0   5   27   0   25   0   2   31   15   105 
Body Weight 
[Units: Kilograms]
Mean (Standard Deviation)
 85.09  (14.25)   86.56  (18.33)   86.67  (17.45)   89.48  (18.06)   86.22  (17.99)   88.84  (14.98)   81.94  (17.67)   85.97  (16.91)   87.07  (16.86)   86.38  (17.28) 
Body Mass Index (BMI) [1] 
[Units: Kilograms per square meter (kg/m^2)]
Mean (Standard Deviation)
 31.02  (4.69)   31.45  (4.88)   31.40  (4.57)   33.89  (4.44)   31.15  (4.44)   32.53  (4.61)   31.06  (3.94)   31.02  (4.20)   31.37  (4.25)   31.27  (4.39) 
[1] BMI is an estimate of body fat based on body weight divided by height squared.
Glycosylated Hemoglobin (HbA1c) 
[Units: Percentage of glycosylated hemoglobin]
Mean (Standard Deviation)
 7.95  (1.11)   8.36  (1.04)   8.12  (1.05)   7.87  (0.62)   8.19  (1.11)   8.30  (1.34)   7.82  (0.80)   8.09  (1.09)   8.10  (1.14)   8.13  (1.09) 
Duration of Diabetes 
[Units: Years]
Mean (Standard Deviation)
 6.79  (6.34)   6.92  (5.12)   6.95  (5.50)   7.04  (4.57)   7.34  (4.92)   6.75  (3.99)   6.74  (4.20)   7.16  (4.89)   6.96  (5.43)   7.09  (5.12) 
Fasting Plasma Glucose [1] [2] 
[Units: Millimoles per liter (mmol/L)]
Mean (Standard Deviation)
 NA [1]   NA [1]   9.75  (3.27)   NA [1]   9.68  (2.94)   NA [1]   NA [1]   9.56  (2.80)   9.86  (3.15)   NA [2] 
[1] Baseline fasting plasma glucose was not summarized for this treatment arm.
[2] Total Mean (SD) were not calculated for this baseline measure.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Glycosylated Hemoglobin (HbA1c) Change From Baseline   [ Time Frame: Baseline, 52 weeks ]

2.  Secondary:   Change From Baseline in Glycosylated Hemoglobin (HbA1c) at the Dose Decision Point   [ Time Frame: Baseline up to 27.4 weeks ]

3.  Secondary:   Glycosylated Hemoglobin (HbA1c) Change From Baseline   [ Time Frame: Baseline, 26 weeks, 104 weeks ]

4.  Secondary:   Durability of Change From Baseline in Glycosylated Hemoglobin (HbA1c)   [ Time Frame: Baseline, 13, 26, 52, and 104 weeks ]

5.  Secondary:   Fasting Blood Glucose Change From Baseline   [ Time Frame: Baseline, 26, 52, and 104 weeks ]

6.  Secondary:   Fasting Insulin Change From Baseline   [ Time Frame: Baseline, 26, 52, and 104 weeks ]

7.  Secondary:   Change From Baseline in Body Weight at Dose Decision Point   [ Time Frame: Baseline up to 27.4 weeks ]

8.  Secondary:   Body Weight Change From Baseline   [ Time Frame: Baseline, 26, 52, and 104 weeks ]

9.  Secondary:   Durability of Change From Baseline Body Weight   [ Time Frame: Baseline, 13, 26, 52, and 104 weeks ]

10.  Secondary:   Waist Circumference Change From Baseline   [ Time Frame: Baseline, 26, 52, and 104 weeks ]

11.  Secondary:   Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5%   [ Time Frame: Baseline, 26, 52, and 104 weeks ]

12.  Secondary:   Incidence of Hypoglycemic Episodes   [ Time Frame: Baseline through 26 and 104 weeks ]

13.  Secondary:   Rate of Hypoglycemic Episodes   [ Time Frame: Baseline through 26 and 104 weeks ]

14.  Secondary:   Beta Cell Function and Insulin Sensitivity (HOMA2)   [ Time Frame: Baseline, 26, 52, and 104 weeks ]

15.  Secondary:   Number of Participants With Treatment-emergent Adverse Events at 26 Weeks   [ Time Frame: Baseline through 26 weeks ]

16.  Secondary:   Number of Participants With Treatment-emergent Adverse Events at 52 Weeks   [ Time Frame: Baseline through 52 weeks ]

17.  Secondary:   Number of Participants With Treatment-emergent Adverse Events at 104 Weeks   [ Time Frame: Baseline through 104 weeks ]

18.  Secondary:   Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 26 Weeks   [ Time Frame: Baseline through 26 weeks ]

19.  Secondary:   Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 52 Weeks   [ Time Frame: Baseline through 52 weeks ]

20.  Secondary:   Number of Participants With Treatment-emergent Abnormal Laboratory Tests at 104 Weeks   [ Time Frame: Baseline through 104 weeks ]

21.  Secondary:   Number of Participants With Treatment-emergent Abnormal Lipid Tests   [ Time Frame: Baseline through 26 and 104 weeks ]

22.  Secondary:   Change From Baseline in Pulse Rate at Dose Decision Point   [ Time Frame: Baseline up to 27.4 weeks ]

23.  Secondary:   Change From Baseline in Blood Pressure at Dose Decision Point   [ Time Frame: Baseline up to 27.4 weeks ]

24.  Secondary:   Change From Baseline in Pulse Rate   [ Time Frame: Baseline, 26 weeks, 104 weeks ]

25.  Secondary:   Change From Baseline in Blood Pressure   [ Time Frame: Baseline, 26 weeks, 104 weeks ]

26.  Secondary:   Change From Baseline in Electrocardiogram (ECG) Parameters, Fridericia-corrected QT (QTcF) and PR Interval   [ Time Frame: Baseline, 26 weeks, 104 weeks ]

27.  Secondary:   Participant-reported Outcomes, Impact of Weight on Quality of Life-Lite (IWQoL-Lite)   [ Time Frame: Baseline, 52 weeks, and 104 weeks ]

28.  Secondary:   Participant-reported Outcomes, EQ-5D   [ Time Frame: Baseline, 52 weeks, and 104 weeks ]

29.  Secondary:   Resource Utilization   [ Time Frame: Baseline through 52 and 104 weeks ]

30.  Secondary:   Pharmacokinetics of LY2189265: Area Under the Concentration-Time Curve   [ Time Frame: Baseline through 52 weeks ]

31.  Secondary:   Antibodies to LY2189265   [ Time Frame: Baseline through 104 weeks ]

32.  Other Pre-specified:   Number of Participants With Adjudicated Pancreatitis at 104 Weeks   [ Time Frame: Baseline through 104 weeks ]

33.  Other Pre-specified:   Number of Participants With Adjudicated Cardiovascular Events at 104 Weeks   [ Time Frame: Baseline through 104 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI 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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT00734474     History of Changes
Other Study ID Numbers: 11422
H9X-MC-GBCF ( Other Identifier: Eli Lilly and Company )
CTRI/2009/091/000969 ( Registry Identifier: Clinical Trials Registry - India )
Study First Received: August 12, 2008
Results First Received: October 3, 2014
Last Updated: March 31, 2015