A Study of LY2605541 and Insulin Lispro Mixture in Healthy Participants

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate how the body absorbs and removes LY2605541, insulin lispro, and a mixture of both from the blood. The study has two parts. Participants may enroll in only one part. Each part has four treatment periods in a fixed order. The study will last approximately 8 weeks, not including screening. Screening is required within 28 days prior to the start of the study.

Official Title
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A Phase 1 Study to Evaluate the Pharmacokinetics of LY2605541 Injection and Insulin Lispro Injection Administered as Mixture or as Individual Components in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LY2605541
* Drug: Insulin Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are not of child-bearing potential Have a body mass index (BMI) between 18 and 29.9 kilograms per meter squared (kg/m^2), inclusive Are nonsmokers or have not smoked for at least 2 months prior to entering the study Exclusion Criteria: Have known allergies to insulin or its excipients, or related drugs, or history of relevant allergic reactions of any origin Have a history of first-degree relatives known to have diabetes mellitus Have used systemic glucocorticoids within 3 months prior to entry into the study Have donated blood or had a blood loss of 450 milliliter (mL) within 1 month prior to study enrollment

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2605541-Part A<br>1.42 units per kilogram (U/kg) of LY2605541 given once daily (QD) for 1 day, subcutaneously (SQ) in 1 of 4 treatment periods. | Drug: LY2605541<br>* Administered subcutaneous (SQ)<br>|
| Active Comparator: Insulin Lispro-Part A<br>Single dose 0.36 U/kg of insulin lispro given QD for 1 day, SQ in 1 of 4 treatment periods. | Drug: Insulin Lispro<br>* Administered SQ<br>* Other names: Humalog;|
| Experimental: LY2605541/Lispro Mix 1-Part A<br>Single dose 0.54 U/kg of LY2605541 and 0.36 U/kg insulin lispro mixture given QD for 1 day, SQ in 1 of 4 treatment periods. | Drug: LY2605541<br>* Administered subcutaneous (SQ)<br>Drug: Insulin Lispro<br>* Administered SQ<br>* Other names: Humalog;|
| Experimental: LY2605541/Lispro Mix 2-Part A<br>Single dose 1.42 U/kg of LY2605541 and 0.36 insulin lispro mixture given QD for 1 day, SQ in 1 of 4 treatment periods. | Drug: LY2605541<br>* Administered subcutaneous (SQ)<br>Drug: Insulin Lispro<br>* Administered SQ<br>* Other names: Humalog;|
| Active Comparator: Insulin Lispro-Part B<br>0.18 U/kg insulin lispro given twice daily (BID) for 1 day, SQ in 1 of 4 treatment periods. Part B is contingent on data from Part A. | Drug: Insulin Lispro<br>* Administered SQ<br>* Other names: Humalog;|
| Experimental: LY2605541/Lispro Mix-Part B<br>0.71 U/kg LY2605541 and 0.18 U/kg insulin lispro mixture given BID for 1 day, SQ in 1 of 4 treatment periods. Part B is contingent on data from Part A. | Drug: LY2605541<br>* Administered subcutaneous (SQ)<br>Drug: Insulin Lispro<br>* Administered SQ<br>* Other names: Humalog;|
| Experimental: LY2605541 QD-Part B<br>0.54 U/kg of LY2605541 given QD for 1 day, SQ in 1 of 4 treatment periods. Part B is contingent on data from Part A. | Drug: LY2605541<br>* Administered subcutaneous (SQ)<br>|
| Experimental: LY2605541 BID-Part B<br>0.71 U/kg of LY2605541 given BID for 1 day SQ in 1 of 4 treatment periods. Part B is contingent on data from Part A. | Drug: LY2605541<br>* Administered subcutaneous (SQ)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Time to Reach Peak Concentration (tmax) of LY2605541 and Insulin Lispro |  | Pre-dose up to 216 hours post-dose | 
| Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of LY2605541 and Insulin Lispro |  | Pre-dose up to 216 hours post-dose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC0-∞) of LY2605541 and Insulin Lispro |  | Pre-dose up to 216 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Glucose Infusion Rate (Rmax) |  | Predose up to 32 hours post clamp procedure in all treatment periods | 
| Total Glucose Infused Over Clamp Duration (Gtot) |  | Predose up to 32 hours post clamp procedure in all treatment periods |