A Study of LY3457263 Alone and in Combination With Dulaglutide (LY2189265) in Participants With Type 2 Diabetes

Study Overview
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Brief Summary
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The main purpose of this study is to investigate the safety and tolerability of the study drug LY3457263 when administered alone or in combination with glucagon-like peptide 1 (GLP-1) receptor agonist (RA) in participants with type 2 diabetes. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. The study will last up to approximately 16 weeks excluding the screening period for each participant and include up to 17 visits.

Official Title
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Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3457263 Alone and in Combination With GLP-1 RA in Patients With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: LY3457263
* Drug: Placebo
* Drug: Dulaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with type 2 diabetes (T2D) at least 6 months before screening Participants treated for T2D with diet and exercise, with or without metformin Have a glycated hemoglobin A1c (HbA1c) value of ≥ 7.5% and ≤10.5% Have had a stable body weight for 3 months and body mass index (BMI) of 27.0 to 45.0 kilograms per meter squared (kg/m²) Male participants who agree to use effective methods of contraception and female participants not of childbearing potential Exclusion Criteria: Have a history of or current cardiovascular, respiratory, hepatic, renal, GI, endocrine (apart from T2D), hematological, or neurological disorders capable of altering the absorption, metabolism, or elimination of drugs Have type 1 diabetes mellitus or latent autoimmune diabetes in adults or maturity-onset diabetes of the young Have a history of proliferative diabetic retinopathy, diabetic maculopathy, or severe non-proliferative diabetic retinopathy Have known allergies to GLP-1 receptor agonists

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3457263 (Alone)<br>LY3457263 administered subcutaneously (SC). | Drug: LY3457263<br>* Administered SC.<br>|
| Placebo Comparator: Placebo (Alone)<br>Placebo administered SC. | Drug: Placebo<br>* Administered SC.<br>|
| Experimental: LY3457263 + Dulaglutide<br>LY3457263 in combination with dulaglutide administered SC. | Drug: LY3457263<br>* Administered SC.<br>Drug: Dulaglutide<br>* Administered SC.<br>* Other names: LY2189265;|
| Experimental: Placebo + Dulaglutide<br>Placebo in combination with dulaglutide administered SC. | Drug: Placebo<br>* Administered SC.<br>Drug: Dulaglutide<br>* Administered SC.<br>* Other names: LY2189265;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Predose up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK: Area Under the Concentration Versus Time Curve (AUC) of LY3457263 | PK: AUC of LY3457263 | Pre-dose on Day 1 up to 85 days post-dose |