A Study of Investigational Dulaglutide Doses in Participants With Type 2 Diabetes on Metformin Monotherapy

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 investigational doses of dulaglutide in participants with type 2 diabetes on metformin monotherapy.

Official Title
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A Phase 2, Double-Blind, Placebo-Controlled, 18-Week Trial of Investigational Dulaglutide Doses Versus Placebo in Patients With Type 2 Diabetes on Metformin Monotherapy

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Dulaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have had type 2 diabetes (T2D) for ≥6 months according to the World Health Organization (WHO) classification Have HbA1c of 7.0% to 10.0%, inclusive, as assessed by the central laboratory Have been treated with stable doses of metformin for at least 3 months Have a body mass index (BMI) ≥25 kilograms per square meter Exclusion Criteria: Have type 1 diabetes (T1D) Have used any glucose-lowering medication other than metformin 3 months prior to study entry or during screening/lead-in period or have used any glucagon-like peptide-1 receptor agonists (GLP-1 RAs) at any time in the past Have had any of the following cardiovascular conditions: acute myocardial infarction (MI), New York Heart Association Class III or Class IV heart failure, or cerebrovascular accident (stroke) Have acute or chronic hepatitis, signs and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >2.5 times the upper limit of the reference range, as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial Have had chronic or acute pancreatitis any time prior to study entry Have an estimated glomerular filtration rate (eGFR) <45 milliliters/minute/1.73 square meter, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation Have serum calcitonin ≥20 picograms per milliliter, as determined by the central laboratory at study entry

Ages Eligible for Study
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Minimum Age: 18 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 4.5mg<br>4.5mg of Dulaglutide administered subcutaneously (SC) | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|
| Experimental: Dulaglutide 3.0mg<br>3.0mg of Dulaglutide administered SC | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|
| Active Comparator: Dulaglutide 1.5mg<br>1.5mg of Dulaglutide administered SC | Drug: Dulaglutide<br>* Administered SC<br>* Other names: LY2189265;|
| Placebo Comparator: Placebo<br>Placebo administered SC | Drug: Placebo<br>* Administered SC<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) | HbA1c is the glycosylated fraction of hemoglobin A. HbA1c 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 as a covariate, pooled country, treatment, time, treatment*time as fixed effects. | Baseline, Week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With HbA1c of <7.0% | Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. | Week 18 | 
| Change From Baseline in Fasting Serum Glucose (FSG) | Fasting serum glucose (FSG) is a test to determine how much glucose (sugar) is in a serum sample after an overnight fast. Least Squares (LS) means was determined by MMRM methodology with baseline as a covariate, pooled country, baseline HbA1c strata using >=8% as cutoff, treatment, time, treatment*time as fixed effects. | Baseline, Week 18 | 
| Change From Baseline in Body Weight | Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline as a covariate, pooled country, baseline HbA1c strata using >=8% as cutoff, treatment, time, treatment*time as fixed effects. | Baseline, Week 18 | 
| Percentage of Participants Discontinuing Study Drug Due to Adverse Events | Adverse event (AE) defined as any unfavorable medical event, newly emerged or a deterioration of a preexisting condition, in other words any untoward medical occurrence in a patient administered a pharmaceutical product, without regard to the possibility of a causal relationship, that occurred after the visit for informed consent and up to the visit for completion of administration, or discontinuation. | Baseline through Week 18 | 
| Rate of Documented Symptomatic Hypoglycemia | Hypoglycemic events (HE) were classified as severe, documented symptomatic (defined as an HE with typical symptoms of hypoglycemia and a blood glucose level of ≤3.9 millimoles per liter [mmol/L]). Hypoglycemia rate per 30 days was summarized at each visit by treatment group. The rate of hypoglycemia was analyzed using a generalized estimation equations model with a negative binomial distribution and a Log link. LS mean was determined by MMRM methodology with baseline hypoglycemia rate, pooled country, HbA1c at Baseline, treatment, with log of exposure in days divided by 365.25 as the offset. | Week 18 | 
| Pharmacokinetics (PK): The Maximum Drug Concentration at Steady State (Cmax,ss) of Dulaglutide | Plasma samples for PK analysis were combined measure obtained from 0, 2, 4, 6, 10, 18, 22 weeks and until early termination of the visit. Cmax takes all time points post dose into account and one value was reported. | 0, 2, 4, 6, 10, 18, 22 weeks and early termination | 
| Pharmacokinetics: Area Under the Concentration-Time Curve at Steady State From Time Zero to 168 Hours (AUC[0-168], ss) of Dulaglutide | AUC[0-168h] is a combined measure obtained from 0, 2, 4, 6, 10, 18, 22 weeks and until early termination of the visit. | 0, 2, 4, 6, 10, 18, 22 weeks and early termination |