A Study of LY2405319 in Participants With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: LY2405319; Placebo
Intervention description: Administered SC; Administered SC
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The main purpose of this study was to evaluate the safety and tolerability of LY2405319. It
      was given as a daily injection under the skin to participants with type 2 diabetes mellitus
      (T2DM) for 28 days. This study determined how long the drug stays in the body and how it
      affects blood sugar levels. After screening, the study lasted about 2 months for each
      participant. Participants continued their prestudy regimen of diet and exercise alone or in
      combination with metformin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of T2DM.

          -  Are on diet and exercise or diet, exercise, and metformin (stable dose of at least
             1000 mg/day for at least 60 days) regimen.

          -  Have a glycosylated hemoglobin A1c (HbA1c) value of 7.0% to 10.0%, inclusive, or are
             on metformin and an additional oral antidiabetic medication (OAM) with an HbA1c value
             of 6.5% to 9.5%, inclusive.

          -  Participants on another OAM in addition to metformin therapy may be randomized if
             removed from treatment of the other OAM ≥14 days prior to study drug administration
             and fasting blood glucose is ≥145 mg per deciliter (mg/dL) and ≤270 mg/dL.

          -  Are females not of child-bearing potential due to surgical sterilization or are
             postmenopausal.

          -  Have a body mass index (BMI) ≥25 and ≤40.

          -  Have clinical laboratory test results within normal reference range for the
             population.

        Exclusion Criteria:

          -  Use insulin, thiazolidinediones (TZDs), dipeptidyl peptidase (DPP) IV inhibitors, or
             exenatide during the 3 months prior to screening.

          -  Have had more than 1 episode of severe hypoglycemia requiring assistance of another
             person to administer a resuscitative action within 6 months prior to entry into the
             study or are currently diagnosed with having hypoglycemia unawareness.

          -  Have had 2 or more emergency room visits or hospitalizations due to poor glucose
             control in the past 6 months.

          -  Have any abnormality of the electrocardiogram (ECG) that will, in the opinion of the
             investigator, impair the ability to measure the QT (a corrected QC [QTc] [Bazett's
             correction] interval >450 milliseconds [msec] for men and >470 msec for women or a PR
             interval >220 msec are specifically excluded) or have conduction abnormalities that
             may confound the QTc analysis.

          -  Have a personal or family history of long QT syndrome, family history of sudden death,
             personal history of unexplained syncope within the last year; or use prescription or
             over-the-counter medications known to prolong the QT or QTc interval.

          -  Have diastolic blood pressure (DBP) ≥95 millimeters of mercury (mm Hg) and/or systolic
             blood pressure (SBP) ≥160 mm Hg.

          -  Have an active or untreated malignancy or have been in remission from a clinically
             significant malignancy for <5 years.

          -  Have a history of a transplanted organ.

          -  Evidence of a significant active, uncontrolled endocrine or autoimmune abnormality, as
             judged by the investigator, at screening.

          -  Have a history of human immunodeficiency virus (HIV).

          -  Have a known allergy to yeast or yeast proteins, history of anaphylaxis with
             bronchospasm, or atopic dermatitis with chronic urticaria.

          -  Have any other condition (including known drug or alcohol abuse or psychiatric
             disorder within the last 6 months) that may preclude the participant from following
             and completing the protocol.

          -  Have a significant history of or current cardiovascular, respiratory, hepatic, renal,
             gastrointestinal, endocrine (including pancreatitis), 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.

          -  Are women who are breastfeeding.

          -  Have had a significant change in weight, defined as a gain or loss of at least 4
             kilograms (kg) (9 pounds) in the 90 days prior to randomization.

          -  Have taken in the 30 days prior to randomization, a medication, herbal product, or
             nutritional supplement that affects adipose mass or distribution or energy balance.

          -  Are receiving chronic (>2 weeks) systemic glucocorticoid therapy (excluding topical or
             inhaled preparations) or have received such therapy within 4 weeks immediately prior
             to second screening appointment.

          -  Have current or recent (within the past 3 months) use of gemfibrozil or fenofibrate,
             niacin, ezetimibe, or bile acid binding resins (for example, cholestyramines). Stable
             statin therapy of ≥3 months will be allowed.

          -  Are currently taking central nervous system (CNS) stimulant.