A Study of Insulin Peglispro (LY2605541) in Participants With Type 2 Diabetes Mellitus

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to compare the efficacy and safety of a new basal insulin, insulin peglispro, to insulin glargine in participants with type 2 diabetes mellitus (T2DM). Both drugs will be given by an injection under the skin. Participants may continue to take oral antihyperglycemic medication (OAM) during the study, as prescribed by their personal physician. The study is expected to last about 12 months for each participant.

Official Title
-----------------
A Comparison of LY2605541 Versus Insulin Glargine as Basal Insulin Treatment in Combination With Oral Anti-Hyperglycemia Medications in Insulin-Naïve Patients With Type 2 Diabetes Mellitus: An Open-Label, Randomized, 52-week Study

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Drug: Insulin Peglispro
* Drug: Insulin Glargine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have T2DM (per World Health Organization [WHO] Classification of Diabetes) not treated with insulin. Have had diabetes for at least 1 year. Have been receiving at least 2 oral antihyperglycemic medications (OAMs) for at least 3 months prior to the study. Have hemoglobin A1c (HbA1c) of 7.0% to 11.0%, inclusive, according to central lab at screening. Have body mass index (BMI) ≤40 kilogram/square meter (kg/m^2). This inclusion criterion applies to females of child-bearing potential (not surgically sterilized and between menarche and 1-year postmenopausal) only: are not breastfeeding, test negative for a serum pregnancy test, intend not to become pregnant during study or willing to have a reliable method of birth control. Exclusion Criteria: Insulin therapy: have used insulin therapy (outside of pregnancy) anytime in the past 2 years, except for short-term treatment of acute conditions, and up to a maximum of 4 continuous weeks. Insulin use of any duration during pregnancy is not considered an exclusion criterion. Concomitant medications: rosiglitazone, pramlintide, glucagon-like peptide-1 (GLP-1) receptor agonist (for example, exenatide, exenatide once weekly, or liraglutide) used concurrently or within 3 months prior to screening. Local OAM restrictions: for participants on OAMs, restrictions for cardiac, renal, hepatic diseases and maximum dose, local product regulations must apply. Weight loss medications: are currently taking, or have taken within the 3 months preceding screening, prescription or over-the-counter medications to promote weight loss. Severe hypoglycemia history: have had any episodes of severe hypoglycemia within 6 months prior to screening. Diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar nonketotic coma (HHNKC): have had 1 or more episodes of DKA or hyperosmolar state/coma in the past 6 months. Cardiovascular: have cardiac disease with functional status that is New York Heart Association Class III or IV (per New York Heart Association [NYHA] Cardiac Disease Classification). Renal: have a history of renal transplantation, or are currently receiving renal dialysis or have serum creatinine ≥2 milligram/deciliter (mg/dL) (177 micromole/liter [mol/L]). Hepatic: have obvious clinical signs or symptoms of liver disease (excluding non-alcoholic fatty liver disease [NAFLD]), acute or chronic hepatitis, non-alcoholic steatohepatitis (NASH), or elevated liver enzyme measurements. Lipid-lowering medications: Are using niacin preparations as a lipid-lowering medication or bile acid sequestrants within 90 days prior to screening; or, Are using lipid-lowering medication at a dose that has not been stable for ≥90 days prior to screening.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2605541<br>LY2605541 administered by subcutaneous (SQ) injection once daily for 52 weeks. Initial dose is 10 units (10 U) and is titrated by investigator. Participants may continue oral antihyperglycemic medication (OAM) as prescribed by their personal physician. | Drug: Insulin Peglispro<br>* Administered SQ<br>* Other names: LY2605541;|
| Active Comparator: Insulin Glargine<br>Insulin glargine administered by SQ injection once daily for 52 weeks. Initial dose is 10 U and is titrated by investigator. Participants may continue OAM as prescribed by their personal physician. | Drug: Insulin Glargine<br>* Administered SQ<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Hemoglobin A1c (HbA1c) at 26 Week Endpoint |  | Baseline, 26 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants with HbA1c ≤6.5% and <7.0% |  | Week 26 and Week 52 | 
| Proportion of Participants with HbA1c <7.0% Without Nocturnal Hypoglycemia Event |  | Baseline through 26 Weeks and Baseline through 52 Weeks | 
| Rate of Total and Nocturnal Hypoglycemia Events |  | Baseline to 26 Weeks | 
| Fasting Serum Glucose (FSG) by Laboratory Measurements |  | 26 Weeks | 
| 9 Point Self Monitored Blood Glucose |  | 26 Weeks | 
| Change from Baseline in Body Weight at Week 26 Endpoint |  | Baseline, 26 Weeks | 
| Change from Baseline in HbA1c at 52 Week Endpoint |  | Baseline, Week 52 | 
| Insulin Dose by Unit |  | 26 Weeks | 
| Time to Reach Steady-State |  | Baseline through 52 Weeks | 
| Fasting Blood Glucose by Self Monitoring |  | Baseline through 52 Weeks | 
| Intra-Participant Variability in Fasting Blood Glucose |  | Baseline through 52 Weeks | 
| Change from Baseline in EuroQol-5 Dimension Questionnaire (EQ-5D) Score |  | Baseline, Week 26, Week 52 | 
| Change from Baseline in the Low Blood Sugar Survey (LBSS) |  | Baseline, Week 26, Week 52 | 
| Number of Participants Developing Anti-Insulin Peglispro Antibodies |  | Week 26 and Week 52 | 
| Change from Baseline in Lipid Profile |  | Baseline, Week 26 |