A Study of U-500 Insulin (LY041001) in Participants With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: U-500R
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin, Isophane
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No

Summary:

      The purpose of this two-part study is to measure how much of the study drug gets into the
      blood stream and how long it takes the body to get rid of it. In Part A, each participant
      will receive two treatments, a single dose and a single dose with continuous infusion of
      U-500R insulin, both administered just under the skin. Participants who complete Part A will
      continue into Part B where they will be assigned to 1 of 2 treatments with U-500R insulin,
      injected either twice or three times daily under the skin for 5-10 days. This study can last
      from 7-14 weeks including initial screening and follow up.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females with type 2 diabetes mellitus (T2DM)

          -  Are current users of U-100, U-200 and/or U-300 insulin/analog as, basal, premixed
             and/or basal/bolus delivered with any injection device (pens and/or syringe/vial but
             excluding continuous subcutaneous infusion (CSII)/insulin pump use in the preceding 3
             months), taking a total daily dose (TDD) of greater than or equal to (≥) 150 units (U)
             or at least one dose greater than (>) 100 U as part of a multiple daily injection
             (MDI) regimen and TDD less than or equal to (≤)3.0 units per kilogram (U/kg)

          -  Concomitant antihyperglycemic agent(s) (AHA) therapy may include: metformin (MET),
             dipeptidyl peptidase 4 inhibitors, pioglitazone (doses ≤30 milligrams per day
             (mg/day)), glucagon like peptide (GLP)-1 receptor agonists, sodium-glucose
             co-transporter-2 (SGLT2) inhibitors, except in combination with GLP-1 receptor
             agonists

          -  Participant's antihyperglycemic agent (AHA) therapy must have been stable for ≥3
             months (except for weekly GLP-1 receptor agonists which must have been stable for ≥4
             months)

          -  Have hemoglobin A1c (HbA1c) 7.5-11.5 percent (%)

        Exclusion Criteria:

          -  Have type 1 diabetes mellitus (T1DM), or other types of diabetes mellitus apart from
             T2DM

          -  Have known hypersensitivities or allergies to insulin, excipients contained in insulin
             products, or related compounds

          -  Have used U-500R within 3 months prior to screening

          -  Have used rosiglitazone, pramlintide, once weekly or twice daily exenatide, or other
             injectable or oral antihyperglycemic agent(s) not listed in the inclusion criterion;
             or are taking oral antidiabetic medications at doses exceeding the respective product
             labels

          -  Have had a blood transfusion or severe blood loss within 3 months prior to screening
             or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia which may
             affect reliability of HbA1c measurements