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

Study Overview
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Brief Summary
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This was a 52-week, multicenter, non-randomized, open-label, Phase 3 long-term safety study in participants with type 2 diabetes mellitus who have inadequate glycemic control with monotherapy of oral antihyperglycemic medication (OAM).

Official Title
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A 52-Week, Open-Label, Long-Term Safety Study of LY2189265 in Combination With Monotherapy of Oral Antihyperglycemic Medications in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: LY2189265
* Drug: Sulfonylureas (SU)
* Drug: Biguanides (BG)
* Drug: alpha-glucosidase inhibitor (a-GI)
* Drug: Thiazolidinedione (TZD)
* Drug: Glinides


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who have had a diagnosis of type 2 diabetes mellitus before screening Participants who have been taking SU (Glibenclamide, Gliclazide, Glimepiride), BG, TZD, a-GI or glinides monotherapy for at least 3 months before screening and have been on a stable dose for at least 8 weeks before screening Participants must have a qualifying HbA1c value of 7.0% to 11.0% at screening Participants who have a body mass index (BMI) of 18.5 to 35.0 kilograms per meter squared (kg/m^2) Exclusion Criteria: Participants who have a diagnosis of type 1 diabetes Participants who have previously been treated with any other glucagon-like peptide-1 (GLP-1) analog within the 3 months before screening Participants who are currently taking insulin or have had previous insulin treatment within the 3 months before screening Participants who have obvious clinical signs or symptoms of pancreatitis, a history of chronic pancreatitis, or acute pancreatitis at screening, as determined by the investigator. Participants who have a serum amylase concentration ≥3 times the upper limit of the reference range and/or a serum lipase concentration ≥2 times the upper limit of the reference range, as determined by the central laboratory at screening Participants who have self or family history of medullary C-cell hyperplasia, focal hyperplasia, or medullary thyroid carcinoma (MTC)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2189265 + Sulfonylureas (SU)<br>LY2189265: 0.75 milligrams (mg) administered subcutaneously (SC), once weekly for 52 weeks Participants were to continue on their stable, pre-study, physician-prescribed dose of SU monotherapy throughout the study. | Drug: LY2189265<br> <br> * Other names: Dulaglutide;Drug: Sulfonylureas (SU)<br>* SU is a pre-study prescribed dose and is not being provided as part of the trial.<br>|
| Experimental: LY2189265 + Biguanides (BG)<br>LY2189265: 0.75 mg administered SC, once weekly for 52 weeks Participants were to continue on their stable, pre-study, physician-prescribed dose of BG monotherapy throughout the study. | Drug: LY2189265<br> <br> * Other names: Dulaglutide;Drug: Biguanides (BG)<br>* Biguanides is a pre-study prescribed dose and is not being provided as part of the trial.<br>|
| Experimental: LY2189265 + alpha-glucosidase inhibitor (a-GI)<br>LY2189265: 0.75 mg administered SC, once weekly for 52 weeks Participants were to continue on their stable, pre-study, physician-prescribed dose of a-GI monotherapy throughout the study. | Drug: LY2189265<br> <br> * Other names: Dulaglutide;Drug: alpha-glucosidase inhibitor (a-GI)<br>* a-GI is a pre-study prescribed dose and is not being provided as part of the trial.<br>|
| Experimental: LY2189265 + Thiazolidinedione (TZD)<br>LY2189265: 0.75 mg administered SC, once weekly for 52 weeks Participants were to continue on their stable, pre-study, physician-prescribed dose of TZD monotherapy throughout the study. | Drug: LY2189265<br> <br> * Other names: Dulaglutide;Drug: Thiazolidinedione (TZD)<br>* TZD is a pre-study prescribed dose and is not being provided as part of the trial.<br>|
| Experimental: LY2189265 + Glinides<br>LY2189265: 0.75 mg administered SC, once weekly for 52 weeks Participants were to continue on their stable, pre-study, physician-prescribed dose of glinides monotherapy throughout the study. | Drug: LY2189265<br> <br> * Other names: Dulaglutide;Drug: Glinides<br>* Glinides is a pre-study prescribed dose and is not being provided as part of the trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) | A TEAE was defined as an event that first occurs or worsens (increases in severity) after baseline, regardless of causality or severity. The percentage of participants with TEAEs was calculated by dividing the number of participants with at least 1 TEAE over the 52-week treatment period by the total number of participants analyzed, multiplied by 100%. A summary of serious and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. | Baseline through 52 Weeks | 
| Percentage of Participants With Hypoglycemic Episodes | The percentage of participants with hypoglycemic episodes was calculated by dividing the number of participants with at least 1 hypoglycemic episode over the 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. | Baseline through 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) |  | Baseline, up to 26 Weeks and up to 52 Weeks | 
| Percentage of Participants Who Achieve HbA1c ≤6.5% or <7% |  | 26 weeks and 52 weeks | 
| Change From Baseline in Fasting Blood Glucose (FBG) |  | Baseline, up to 26 weeks and up to 52 weeks | 
| Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) | 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. For the mean of all 7-point blood glucose values, the daily mean was calculated as the average of 7 blood glucose values collected on a particular day. The mean of all 7-point blood glucose values at each visit was calculated as the average of 2 daily means. The change from baseline was calculated as the mean of all 7-point blood glucose values at endpoint minus the mean of all 7-point blood glucose values at baseline. | Baseline, up to 26 weeks and up to 52 weeks | 
| Change From Baseline in Body Weight |  | Baseline, up to 26 weeks and up to 52 weeks | 
| Change From Baseline in Updated Homeostasis Model Assessment (HOMA2) | The HOMA2 is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady state pancreatic beta cell function (%B) and to estimate insulin sensitivity (%S) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. The change from baseline for fasting insulin concentrations are presented as insulin secretion (HOMA2-%B) and insulin sensitivity (HOMA2-%S). | Baseline, up to 26 weeks and up to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, Oral antihyperglycemic medications, Long-Term Safety, GLP 1, Glucagon like peptide 1