A Study of LY3025876 in Participants With Diabetes

Study Overview
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Brief Summary
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The main purpose of this study is to assess the safety and tolerability of LY3025876 given alone (Part A) and in combination with liraglutide (Part B) in participants with type 2 diabetes mellitus (T2DM).

Detailed Description
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This study will also evaluate how much of the study drug enters the blood stream and how long it takes for the body to remove the study drug. Information about any side effects that may occur will also be collected. Participants will continue their usual diet and exercise program and may remain on their physician-prescribed dose of metformin. Each part of the study is expected to last 10 to 12 weeks on average, not including screening. Participants may only enroll in one part.

Official Title
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Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of LY3025876 in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: LY3025876
* Drug: Placebo
* Drug: Liraglutide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of type 2 diabetes mellitus (T2DM) as determined by the investigator, controlled with diet or exercise alone or on a stable dose of metformin for at least 30 days Have a body mass index (BMI) greater than or equal to 23 and less than or equal to 45 kilograms per square meter (kg/m^2) at screening Have a supine blood pressure reading at screening of between 90-160 millimeter of mercury (mmHg) (systolic) and 40-95 mmHg (diastolic) Women not of child-bearing potential due to surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation) or menopause Exclusion Criteria: Have taken LY3025876 or investigational drugs like it (for example, other fibroblast growth factor-21 [FGF21]-related drugs) or have known allergies to these drugs History or presence of bone disease (including osteoporosis or unhealed fractures) Current active treatment of periodontal disease Have had a significant change in weight, defined as a gain or loss of at least 4 kilogram (kg) (9 pounds) in the last 3 months Have had greater than 1 episode of severe hypoglycemia within 6 months of screening that required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions or had a seizure or coma Have known allergies or a history of intolerance to liraglutide, glucagon-like peptide 1 (GLP-1) analogues, or other related compounds Have a history of acute or chronic pancreatitis Have a personal or family history of medullary thyroid carcinoma or have multiple endocrine neoplasia syndrome type 2

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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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: LY3025876<br>Part A: 0.5 milligram (mg), 1.5 mg, 5 mg, and 15 mg of LY3025876 administered as once daily (QD) subcutaneous (SQ) injections for up to 28 days. | Drug: LY3025876<br>* Administered SQ<br>|
| Placebo Comparator: Placebo<br>Part B: Placebo matching LY3025876 administered as QD SQ injections for up to 28 days | Drug: Placebo<br>* Administered SQ<br>|
| Experimental: LY3025876 + Liraglutide<br>Part B: 5.0 mg of LY3025876 and 1.8 mg liraglutide administered as separate QD SQ injections for up to 28 days, after titration of liraglutide over 2 weeks. | Drug: LY3025876<br>* Administered SQ<br>Drug: Liraglutide<br>* Administered SQ<br>|
| Placebo Comparator: Placebo + Liraglutide<br>Part B: Placebo doses matching LY3025876 and 1.8 mg liraglutide administered as separate QD SQ injections for up to 28 days, after titration of liraglutide over 2 weeks. | Drug: Placebo<br>* Administered SQ<br>Drug: Liraglutide<br>* Administered SQ<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 other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section. | Predose on Day 1 up to Day 56 in each Part | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve From Time 0 to 24 Hours (AUC[0-24]) of LY3025876 | AUC(0-24) of individual participants was calculated by equation Area Under Concentration (AUC)=Dose/CL, where the clearance (CL) was estimated using a population PK model. | Predose and 0.5 hour(hr), 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, and 24 hr Postdose | 
| PK: Maximum Concentration (Cmax) of LY3025876 |  | Days 1 and 28: Predose and 0.5 hr, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, and 24 hr Postdose | 
| Part A and Part B: Immunogenicity: The Number of Participants With Anti-LY3025876 Antibodies |  | Predose on Day 7, 14, 28, 56, and 180 | 
| Pharmacodynamics (PD): Change From Baseline to Day 28 in Fasting Glucose | Least Squares Mean (LS) Mean change from baseline in fasting glucose was modeled using Mixed Effect Model Repeat Measurement (MMRM) analysis with fixed effects of baseline, treatment, day, treatment*day interaction, and participant as a random effect. | Baseline, Day 28 |