A Study of LY3298176 in Healthy Participants and Participants With Type 2 Diabetes (T2DM)

Study Overview
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Brief Summary
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The main purposes of this study are to determine: The safety of LY3298176 and any side effects that might be associated with it. How much LY3298176 gets into the bloodstream and how long it takes the body to get rid of it. How LY3298176 affects the levels of blood sugar. This study includes 3 parts (A, B and C). Part A involves a single dose of LY3298176 taken as a subcutaneous (SC) injection just under the skin and will be approximately 10 weeks in duration, including screening. Parts B and C involve 4 doses of LY3298176 taken once weekly (over 4 weeks) as a SC injection just under the skin and is approximately 12-14 weeks in duration, including screening. Each participant will enroll in only one part. This study is for research purposes only, and is not intended to treat any medical condition.

Official Title
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A Single- and Multiple-Ascending Dose Study in Healthy Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3298176 and Multiple Doses in Patients With Type 2 Diabetes Mellitus

Conditions
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Healthy, Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Drug: LY3298176
* Drug: Placebo
* Drug: Dulaglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy participants (Parts A and B) and participants with T2DM diagnosed at least 1 year before enrollment (Part C) Have a screening body mass index (BMI) of greater than 18.5 and less than or equal to 40.0 kilograms per meter squared (kg/m²), inclusive Participants with T2DM (Part C only): have T2DM controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (metformin for at least 30 days or sulfonylureas). Participants receiving sulfonylureas may participate only if this treatment is stopped for at least 6 weeks before dosing with study drug Exclusion Criteria: Have known allergies to LY3298176, glucagon-like peptide (GLP)-1 analogs, or related compounds Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participating in the study Have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis), elevation in serum amylase or lipase (greater than 2-fold the upper limit of normal [ULN]) or gastrointestinal (GI) disorder (for example, relevant esophageal reflux or gall bladder disease) or any GI disease which impacts gastric emptying (for example, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or dipeptidyl peptidase (DPP)-IV inhibitors Participants with T2DM (Part C only) Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before entry into the study or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms All Study Participants (Parts B and C only) have known allergies to LY3298176, GLP-1 analogs, or related compounds, or acetaminophen

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: LY3298176 (Part A)<br>Escalating doses of LY3298176 administered subcutaneously (SC) once in healthy participants. | Drug: LY3298176<br>* Administered SC<br>|
| Placebo Comparator: Placebo (Part A)<br>Placebo administered SC once in healthy participants. | Drug: Placebo<br>* Administered SC<br>|
| Experimental: LY3298176 (Part B)<br>Escalating doses of LY3298176 administered SC once weekly for four weeks in healthy participants. | Drug: LY3298176<br>* Administered SC<br>|
| Placebo Comparator: Placebo (Part B)<br>Placebo administered SC once weekly for four weeks in healthy participants. | Drug: Placebo<br>* Administered SC<br>|
| Active Comparator: Dulaglutide (Part B)<br>Dulaglutide administered SC once weekly for four weeks in healthy participants | Drug: Dulaglutide<br>* Administered SC<br>* Other names: Trulicity®;|
| Experimental: LY3298176 (Part C)<br>Two dose levels of LY3298176 administered SC once weekly for four weeks in participants with T2DM. | Drug: LY3298176<br>* Administered SC<br>|
| Placebo Comparator: Placebo (Part C)<br>Placebo administered SC once weekly for four weeks in participants with T2DM. | Drug: Placebo<br>* Administered SC<br>|

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 Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline through Day 43 (Part A) or Day 57 (Part B and C) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3298176 | PK: AUC of LY3298176 | Baseline through Day 43 (Part A) or Day 57 (Part B and C) | 
| Pharmacodynamics (PD): AUC of Glucose | PD: AUC of Glucose | Baseline, Day 2 and Day 22 (Part B and C) |