A Study to Compare the Concentrations of LY2189265 After Different Methods of Administration to Healthy Volunteers.
Condition: Diabetes Mellitus, Type II
MeSH terms: Diabetes Mellitus, Type 2
Intervention: LY2189265
Intervention description: administered intravenous, subcutaneous or intramuscular
Intervention MeSH terms: Dulaglutide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      LY2189265 is an investigational drug being developed for the treatment of type 2 diabetes
      mellitus. This study will compare the concentrations of LY2189265 using different methods of
      administration: subcutaneous (or SC- an injection just under the skin), intravenous (or IV -
      into a vein in the arm) and intramuscular (IM - into the muscle of the left thigh). The
      purpose of this study is to look at how much of the drug gets into the blood stream and how
      long it takes the body to get rid of it when given by the methods above. The study is divided
      into three parts, Part A, B and C. Volunteers will only be able to participate in one part.
      All Participants in Part A will receive a single IV dose of up to 0.1 milligram (mg).
      Participants in Part B will be given drug twice by IV and an SC injection (1.5 mg). Part B of
      the study will occur after Part A because the dose of IV drug will depend on the results of
      Part A. Part B of the study may not occur if the volunteers in Part A do not tolerate the
      drug. Participants in Part C will also be given drug twice by an SC injection and an IM
      injection, both doses will be 0.75 mg.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Are overtly healthy males or females, as determined by medical history and physical
             examination.

          -  Male subjects with female partners of child-bearing potential, or partners who are
             pregnant or breastfeeding, agree to use a reliable method of contraception from the
             time of the first dose until 3 months after the last dose of investigational product,
             as determined by the investigator. The method may be one of the following: condom with
             spermicidal agent, male subject sterilization, true abstinence (which is in line with
             the subject's usual lifestyle choice; withdrawal or calendar methods are not
             considered acceptable).

          -  Female subjects not of child-bearing potential (that is, are postmenopausal or
             permanently sterilized [for example, tubal occlusion, hysterectomy, bilateral
             salpingectomy]). Such subjects will not be required to use contraception but must test
             negative for pregnancy at the time of enrollment. Postmenopausal is defined as at
             least 1 year post cessation of menses (without an alternative medical cause) with
             follicle stimulating hormone (FSH) greater than or equal to 40 milli-international
             units per milliliter (mIU/mL).

          -  Female subjects who have undergone sterilization by tubal ligation: agree to use a
             condom in conjunction with spermicidal gel, foam, cream, film or suppository from the
             time of screening until 3 months after the last dose of investigational product. Such
             subjects must also test negative for pregnancy at the time of enrollment.

          -  Have a body mass index (BMI) of between 23.0 and 35.0 kilogram/square meter (kg/m²),
             inclusive.

          -  Have clinical laboratory test results within normal reference range for the population
             or investigator site, or results with acceptable deviations that are judged to be not
             clinically significant by the investigator.

          -  Have normal sitting blood pressure and pulse rate as determined by the investigator,
             or with changes compatible with their age.

          -  Have venous access sufficient to allow for blood sampling and/or IV administration of
             investigational product as per the protocol.

          -  Are reliable and willing to make themselves available for the duration of the study
             and are willing to follow study procedures.

          -  Have given written informed consent approved by Lilly and the ethical review board
             (ERB) governing the site.

        Exclusion Criteria:

          -  Are currently enrolled in, or discontinued within the last 30 days from, a clinical
             trial involving an investigational drug or device, or are concurrently enrolled in any
             other type of medical research judged not to be scientifically or medically compatible
             with this study.

          -  Are women of child bearing potential

          -  Have known allergies to Glucagon-like peptide-1 (GLP-1)-related compounds including
             LY2189265.

          -  Are persons who have previously completed or withdrawn from this study or any other
             study investigating LY2189265.

          -  Have an abnormality in the 12-lead Electrocardiogram (ECG) that, in the opinion of the
             investigator, increases the risks associated with participating in the study.

          -  Have a history or presence of gastrointestinal disorder (including pancreatitis
             [history of chronic pancreatitis or idiopathic acute pancreatitis] or gall bladder
             disease), or gastrointestinal disease that impacts gastric emptying (GE) (for example,
             gastric bypass surgery, pyloric stenosis) or could be aggravated by GLP analogs (for
             example, esophageal reflux). Subjects having had cholecystolithiasis (removal of gall
             stones), cholecystectomy (removal of gall bladder) and/or appendectomy in the past
             with no further sequelae may be included in the study at the discretion of the
             screening physician.

          -  Have a history or presence of significant active neuropsychiatric disease

          -  Regularly use known drugs of abuse and/or show positive findings on urinary drug
             screening.

          -  Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV
             antibodies.

          -  Show evidence of hepatitis C and/or positive hepatitis C antibody.

          -  Show evidence of hepatitis B and/or positive hepatitis B surface antigen.

          -  Are women with a positive pregnancy test or women who are lactating.

          -  Use or intend to use over-the-counter medication other than paracetamol within 7 days
             prior to dosing or prescription medication (with the exception of vitamin/mineral
             supplements and/or hormone replacement therapy and/or thyroid replacement therapy)
             within 14 days prior to dosing.

          -  Have donated blood of more than 500 mL within the last month.

          -  Are subjects who have an average weekly alcohol intake that exceeds 21 units per week
             (males) and 14 units per week (females), (1 unit = 12 ounce [oz] or 360 mL of beer; 5
             oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits), or are unwilling to stop
             alcohol consumption from at least 24 hours prior to screening and each dose, and while
             resident at the clinical research unit (CRU).

          -  Are subjects who smoke more than 10 cigarettes per day, are unwilling to refrain from
             smoking on the day of LY2189265 administration and while resident.

          -  Are subjects who, in the opinion of the investigator, are in any way unsuitable to
             participate in the study.