A Study of LY2605541 and Glargine and Exercise in Participants With Type 1 Diabetes
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: LY2605541; Insulin Glargine
Intervention MeSH terms: Insulin Glargine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to measure how much of the study drug or insulin glargine gets
      into the blood stream and how long it takes the body to get rid of it. The effect of exercise
      will also be evaluated.

      This study has two parts. In Part A, each participant will receive a daily injection of
      LY2605541 or insulin glargine for about 15 days. Some participants may continue into Part B.
      In Part B, participants will receive a daily injection of LY2605541 or insulin glargine with
      or without exercise. Part B lasts about 6 days.

      Participants will remain on their regular physician-prescribed mealtime insulin throughout
      the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are males or females that have had a diagnosis of Type I Diabetes Mellitus (T1DM) for
             at least 12 months and are receiving multiple daily insulin injections. Total daily
             insulin dose <1.2 units per kilogram per day (U/kg/day); daily basal dose >0.2
             U/kg/day

          -  Female participants: are women of child-bearing potential who test negative for
             pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a
             reliable method of birth control during the study

          -  Have a body mass index (BMI) of 18 to 30 kilograms per meter squared (kg/m^2),
             inclusive

          -  Have a fasting c-peptide <0.3 nanomoles per liter (nmol/L)

          -  Have a hemoglobin A1c (HbA1c) <9% at screening

        Participants with T1DM are eligible for enrollment in Part B of the study only if they meet
        all of the following criteria:

          -  Have a maximal oxygen uptake (VO2 max) of ≥25 milliliters (mL) of oxygen per kilogram
             per minute (O2/kg/min) (for women) or ≥30 mL O2/kg/min (for men)

          -  Perform regular physical cardiorespiratory activity to achieve an average total energy
             expenditure of ≥500 metabolic equivalent of task (MET)-minutes per week during the
             last 3 months prior to screening

        Exclusion Criteria:

          -  Have known allergies to LY2605541, insulin glargine, related compounds or any
             components of the formulation

          -  Have a history of or current cardiovascular, respiratory, hepatic, renal,
             gastrointestinal, endocrine (apart from T1DM), hematological, or neurological
             disorders capable of significantly altering the absorption, metabolism, or elimination
             of drugs; of constituting a risk when taking the study medication; or of interfering
             with the interpretation of data

          -  Have had episodes of severe hypoglycemia in the past 6 months (severe hypoglycemia is
             defined as having neurological symptoms consistent with neuroglycopenia and having
             required assistance in treatment by a second party)

          -  Have a history of hypoglycemia unawareness

          -  Regular use or intended use of any over-the-counter or prescription medications or
             nutritional supplements that may affect blood glucose, the body's sensitivity to
             insulin, or that promote weight loss within 14 days prior to dosing

          -  Have an average weekly alcohol intake that exceeds 21 units per week (males up to age
             65) and 14 units per week (males over 65 and females), or are unwilling to comply with
             study requirements regarding alcohol consumption

          -  Currently smokes >5 cigarettes per day, or are unwilling to comply with study
             requirements regarding smoking or use of tobacco products

          -  Have a hemoglobin level <8.0 millimoles per liter (mmol/L) (male) or <6.4 mmol/L
             (female) at screening

          -  Are currently participating in a weight loss program or plan to do so during the
             course of the study

          -  Are receiving chronic (lasting longer than 14 consecutive days) systemic
             glucocorticoid therapy (excluding topical, intra-articular, and intra-ocular
             preparations) or have received such therapy within the 4 weeks before dosing

          -  Have fasting triglycerides >400 milligrams per deciliter (mg/dL) (4.52 mmol/L)

          -  Have previous history or family history of deep vein thrombosis