A Study of Two Doses of Dulaglutide (LY2189265) in Japanese Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of 2 doses of dulaglutide in Japanese participants with type 2 diabetes. The study duration is approximately 58 weeks.

Official Title
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A Randomized, Double-Blind, Parallel Arm Study of the Efficacy and Safety of Two Doses of Dulaglutide in Combination With a Single Oral Antihyperglycemic Medication or as Monotherapy in Japanese Patients With Type 2 Diabetes Mellitus (AWARD-JPN: Assessment of Weekly Administration of LY2189265 in Diabetes - JAPAN)

Conditions
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Diabetes Mellitus, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Metabolic Disease, Endocrine System Diseases, Hypoglycemic Agents, Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Drug: Dulaglutide
* Drug: Oral antihyperglycemics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with type 2 diabetes (T2D) ≥ 6 months according to the World Health Organization (WHO) classification. Treated with stable doses of a single OAM for at least 8 weeks prior to screening; the dose must be more than or equal to minimum maintenance dose. Have the following HbA1c result at screening. Participants taking DPP-4i: ≥7.5% and ≤9.5%, Participants taking another OAM: ≥8.0% and ≤10.0% Stable body weight for at least 8 weeks prior to screening or not changed by more than 5 % in the past 8 weeks Have a body mass index (BMI) ≥18.5 kilogram/square meter (kg/m²) and <35 kg/m² at Day 1. Exclusion Criteria: Have type 1 diabetes (T1D) Have a history of ≥1 episode of ketoacidosis or hyperosmolar state/coma Have had any myocardial infarction (MI), heart failure or cerebrovascular accident (stroke) Have a known clinically significant gastric empty abnormality Have acute or chronic hepatitis Have had chronic or acute pancreatitis Have any self or family history of type 2A or type 2B multiple endocrine neoplasia in the absence of known C-cell hyperplasia Have any self or family history of medullary C-cell hyperplasia, focal hyperplasia, or carcinoma (including sporadic, familial, or part of Multiple endocrine neoplasia (MEN) 2A or 2B syndrome) Have evidence of significant, active autoimmune abnormality Have evidence of significant, uncontrolled endocrine abnormality Have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer) for less than 5 years Have any hematologic condition that may interfere with HbA1c measurement

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dulaglutide 1.5 milligram (mg)<br>Participants received 1.5 mg of dulaglutide given weekly subcutaneously (SC) during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 oral antihyperglycemic medication (OAM). Participants on dipeptidyl peptidase-4 inhibitors (DPP-4i) discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;Drug: Oral antihyperglycemics<br>* Administered orally<br>|
| Active Comparator: Dulaglutide 0.75 mg<br>Participants received 0.75 mg of dulaglutide given weekly SC during the 52-week treatment period. Dulaglutide will be given alone or in combination with 1 OAM. Participants on DPP-4i discontinued DPP-4i at randomization and was regarded as monotherapy of dulaglutide, other OAMs continued at same dose during study period and were regarded as combination therapy with dulaglutide. | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;Drug: Oral antihyperglycemics<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Pre-study oral antihyperglycemic medication (OAM) Group 1 + Treatment + Time + Treatment × Time as variables. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c at Week 52 | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with Baseline + Pre-study OAM Group 1 + Treatment + Time + Treatment × Time as variables. | Baseline, Week 52 | 
| Percentage of Participants Achieving HbA1c Target ≤6.5% and <7.0% | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time. The odds ratios, confidence intervals, and p-values were determined by generalized linear mixed model (GLM) with Baseline + Pre-study OAM Group 1 + Treatment + Time + Treatment × Time as variables. | Week 52 | 
| Change From Baseline in Fasting Serum Glucose (FSG) | FSG is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment + Time + Treatment*Time as variables. | Baseline, Week 52 | 
| Change From Baseline in 6-point Self-Monitored Blood Glucose (SMBG) | SMBG 6-point profiles were measured at morning (premeal-fasting, 2-hour post meal), midday (premeal, 2-hour post meal), and evening (premeal, 2-hour post meal). LS mean was determined by analysis of covariance (ANCOVA) model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment as variables. | Baseline, Week 26 | 
| Change From Baseline in Body Weight | LS mean was determined by MMRM model with Baseline + Baseline HbA1c (High, Low) Group, OAM-based + Pre-study OAM Group 1 + Treatment + Time + Treatment*Time as variables. | Baseline, Week 52 |