A Study of LY900014 in Participants With Type 2 Diabetes on Insulin Injection Therapy

Study Overview
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Brief Summary
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The study will be conducted in participants with type 2 diabetes on insulin injection therapy to investigate how the body processes LY900014 and the effect of LY900014 on blood sugar levels. Side effects and tolerability will be documented. The study will be conducted in two parts (Part A and Part B) to achieve its objectives. Participants are expected to enroll in both parts.

Official Title
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Pharmacokinetics, Glucodynamics, Safety, and Tolerability of LY900014 in Patients With Type 2 Diabetes Mellitus on Multiple Daily Insulin Injection Therapy

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: LY900014
* Drug: Insulin Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are male or female participants with Type 2 Diabetes Mellitus (T2DM) on a stable multiple daily injection regimen with a short-acting as well as a long-acting insulin Have a body mass index (BMI) ranging from 18.5 to 33.0 kilogram per square meter (kg/m²), inclusive, at screening Have blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results acceptable for the study Have had no episodes of severe hypoglycemia in the past 6 months (requiring assistance in treatment by a second party) Have venous access sufficient to allow for blood sampling Have provided written consent and are willing to follow study procedures and commit to the study duration Exclusion Criteria: Are currently enrolled, or have participated within the last 30 days, in a clinical trial or any other type of medical research judged to be incompatible with this study Have previously completed or withdrawn from this study Have or used to have health problems that, in the opinion of the doctor, could make it unsafe to participate in the study Had blood loss of more than 500 milliliters (mL) within the last month Are treated with a continuous subcutaneous insulin infusion (insulin pump)

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY900014 (Part A)<br>Individualized doses of LY900014 administered by injection under the skin once in each of 3 periods | Drug: LY900014<br>* Administered subcutaneously (SC)<br>* Other names: Ultra-Rapid Lispro;|
| Active Comparator: Insulin Lispro - Reference (Part A)<br>Individualized doses of insulin lispro reference formulation administered by injection under the skin once in each of 3 periods | Drug: Insulin Lispro<br>* Administered SC<br>* Other names: LY275585;|
| Experimental: LY900014 (Part B)<br>Individualized doses of LY900014 administered by injection under the skin with each meal for 14 days | Drug: LY900014<br>* Administered subcutaneously (SC)<br>* Other names: Ultra-Rapid Lispro;|
| Active Comparator: Insulin Lispro - Reference (Part B)<br>Individualized doses of insulin lispro reference formulation administered by injection under the skin with each meal for 14 days | Drug: Insulin Lispro<br>* Administered SC<br>* Other names: LY275585;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part A) | PK: Insulin Lispro AUC(0-5h) (Part A) | Day 1: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment | 
| Pharmacokinetics (PK): Insulin Lispro Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) (Part B) | PK: Insulin Lispro AUC(0-5h) (Part B) | Days 1 and 14: 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150,180, 240, 300 minutes post dose for each treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part A) | PD: AUC(0-5h) of Glucose Relative to a MMTT (Part A) | Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes | 
| Pharmacodynamics (PD): Area Under the Concentration Curve From Time Zero to 5 Hours (AUC[0-5h]) of Glucose Relative to a Mixed Meal Tolerance Test (MMTT) (Part B) | PD: AUC(0-5h) of Glucose Relative to a MMTT (Part B) | Days 1 and 14: Day 1: -30, -15, 0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 135, 150, 165, 180, 195, 210, 225, 240, 300 minutes in each study period |