An Administration Method Study of Human Regular U-500 Insulin (LY041001) in Participants With Type 2 Diabetes Mellitus
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Human regular U-500 insulin (CSII); Human regular U-500 insulin (MDI)
Intervention description: Administered SC; Administered SC
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 420.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: insulin pumps; concentrated insulin; OmniPod

Summary:

      The main purpose of this study is to evaluate the efficacy and safety of the study drug known
      as human regular U-500 insulin (U-500R) administered by continuous subcutaneous insulin
      infusion (CSII) versus multiple daily injections (MDI) in participants with type 2 diabetes
      mellitus.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosed with type 2 diabetes mellitus (T2DM).

          -  Current TDD >200 but ≤600 units of non U-500R insulin (MDI or CSII) and/or U-500R by
             MDI with syringe and vial for ≥3 months at entry.

               -  If TDD of U-500R and other insulins are combined, then insulin other than U-500R
                  not to exceed 25% of TDD.

          -  HbA1c ≥7.5% and ≤12.0%.

          -  Body mass index ≥25 but ≤50 kilograms per meter squared.

          -  Have a history of stable body weight.

          -  Concomitant antihyperglycemic agent (AHA) therapy may include metformin (MET),
             dipeptidyl peptidase-4 inhibitors and/or pioglitazone.

               -  Approximately 64 to 96 subjects using glucagon-like peptide-1 (GLP-1) receptor
                  agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors will be enrolled in
                  Study Group B.

        Exclusion Criteria:

          -  Diagnosed with type 1 diabetes mellitus (T1DM) or other types of diabetes apart from
             T2DM.

          -  Have obvious clinical or radiographic signs or symptoms of liver disease (except
             nonalcoholic fatty liver disease), cirrhosis, acute or chronic hepatitis, or alanine
             aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) levels ≥2.5X
             upper limit of normal (ULN), alkaline phosphatase ≥2X ULN or total bilirubin ≥2X ULN.

          -  Have chronic kidney disease Stage 4 and higher or history of renal transplantation.

          -  Have history of more than 1 episode of severe hypoglycemia within the 6 months prior
             to screening.

          -  Have received U-500R insulin by CSII in the 3 months prior to screening.

          -  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.

          -  Are taking chronic (lasting longer than 14 consecutive days) systemic glucocorticoid
             therapy.

          -  Have an irregular sleep/wake cycle.

          -  Have used any weight loss drugs in the 3 months prior to screening.

          -  Have a history of bariatric surgery including Roux-en-Y gastric bypass surgery,
             gastric banding, and/or gastric sleeve.

          -  Have a history of an active or untreated malignancy, or in remission from a clinically
             significant malignancy during the last 5 years before screening.

          -  Significant hearing loss and/or vision impairment deemed by the investigator to
             interfere with the safe use of OmniPod U-500 system.

          -  Have cardiac disease with functional status that is New York Heart Association (NYHA)
             Class III or IV per New York Heart Association Cardiac Disease Functional
             Classification or have congestive heart failure requiring pharmacologic treatment.

          -  Are women breastfeeding or pregnant, or intend to become pregnant during the course of
             the study; are men who intend to impregnate their partners; or are sexually active of
             procreation potential not actively practicing birth control by a method determined by
             the investigator to be medically acceptable. Are investigator site personnel directly
             affiliated with this study and/or their immediate families. Immediate family is
             defined as a spouse, parent, child, or sibling, whether biological or legally adopted.