A Study of the Effect of LY2189265 on Two Blood Pressure Drugs
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Intervention: LY2189265; Metoprolol; Lisinopril; Placebo
Intervention description: Administered subcutaneously; Administered orally; Administered orally; Administered subcutaneously
Intervention MeSH terms: Dulaglutide; Metoprolol; Lisinopril
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is twofold:

        1. To evaluate the effect of LY2189265 on how the body absorbs a blood pressure lowering
           drug (lisinopril) in participants with high blood pressure who are currently taking
           lisinopril.

        2. To evaluate the effect of LY2189265 on heart rate and blood pressure in healthy
           volunteers when taken with a Beta-blocker drug (metoprolol).

      In Part 1, participants will receive four weekly injections of LY2189265 with continued use
      of normal lisinopril therapy.

      Part 2 is a cross-over study design. Participants will receive a single injection of
      LY2189265 in one period, and seven daily doses of metoprolol and a single injection of
      LY2189265 in another period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male participants: agree to use a reliable method of birth control during the study
             and for 3 months following the last dose of the investigational product

          -  Female participants: women not of child-bearing potential due to menopause or surgical
             sterilization (at least 6 weeks post surgical bilateral oophorectomy, hysterectomy or
             tubal ligation) confirmed by medical history

          -  Have a body mass index (BMI) of 18.5 to 40.0 kilograms/square meter (kg/m^2),
             inclusive at the time of screening

          -  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 venous access sufficient to allow for blood sampling as per the protocol

          -  Are reliable and willing to make themselves available for the duration of the study
             and are willing to follow study restrictions

          -  Have given written informed consent on an informed consent form (ICF) approved by
             Lilly and the corresponding ethics committee (EC) or ethical review board (ERB)
             governing the site

        Part 1 only:

          -  Have controlled mild to moderate hypertension (supine blood pressure [BP] less than or
             equal to 140/90 millimeter of mercury (mm Hg) at screening, or results with acceptable
             deviations that are judged not to be clinically significant by the investigator).

          -  Males and females with stable medical problems (including Type 2 Diabetes Mellitus
             [T2DM]) that, in the investigator's opinion, will not significantly alter the
             disposition of the drug, will not place the participant at increased risk by
             participating in the study, and will not interfere with interpretation of the data may
             be included

          -  Have been on oral antihypertensive medication (lisinopril daily [QD]) for at least 3
             months prior to screening, have been on a stable dose for at least 1 month prior to
             screening, and are, in the investigator's opinion, able to safely adhere to a QD
             morning dosing regimen. Additional medication may be permitted as indicated

        T2DM Participants (Part 1 only):

          -  Have T2DM controlled with diet or exercise alone or stable on a single oral agent
             antihyperglycemic medication (metformin, sulfonylureas, repaglinide, nateglinide,
             acarbose [or other disaccharidase inhibitors] or thiazolidinediones) for at least 3
             weeks (3 months for thiazolidinediones) prior to admission

          -  Have a hemoglobin A1c (HbA1c) value of 6.0% to 9.5% at screening or within 4 weeks
             prior to screening

          -  Clinical laboratory test results within normal range or deemed clinically
             insignificant by the investigator. Abnormalities of serum glucose, serum lipids,
             urinary glucose, and urinary protein consistent with T2DM are acceptable

        Part 2 only:

        • Are overtly healthy, as determined by medical history and physical examination

        Exclusion Criteria:

          -  Are currently enrolled in, have completed or discontinued within the last 30 days
             from, a clinical trial involving an investigational product; or are concurrently
             enrolled in any other type of medical research judged not to be scientifically or
             medically compatible with this study

          -  Have known allergies to Glucagon-like peptide-1 (GLP-1)-related compounds, including
             LY2189265, or any components of the formulation

          -  Are participants who have previously completed or withdrawn from this study, or have
             taken part in any other study investigating LY2189265 or GLP-1-related compounds
             within the last 3 months

          -  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) (e.g. gastric
             bypass surgery, pyloric stenosis) or could be aggravated by GLP-1 analogs (for
             example; esophageal reflux). Participants having had cholecystectomy (removal of gall
             bladder) 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 thyroid disease, unless have been on a stable dose of
             thyroxine replacement therapy for at least 1 month

          -  Show history or evidence of significant active neuropsychiatric disease

          -  Have personal or family history of medullary thyroid cancer (MTC) or a genetic
             condition that predisposes to MTC

          -  Regularly use known drugs of abuse and/or show positive findings on urinary drug
             screening

          -  Show evidence of human immunodeficiency virus (HIV) infection 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

          -  Intend to start new concomitant medication during the study, including
             over-the-counter and herbal medication, use drugs that directly reduce
             gastrointestinal motility or who regularly use systemic corticosteroids, or potent,
             inhaled, or intranasal steroids known to have a high rate of systemic absorption

          -  Have donated more than 500 milliliters (mL) of blood within the month prior to
             screening

          -  Have a nondominant arm circumference of greater than 42 centimeters (cm)

          -  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 stop
             alcohol consumption from 48 hours before each admission until discharge from the unit,
             and to limit alcohol intake to a maximum of 2 units/day on all other days from
             screening through 48 hours prior to the follow-up visit. (1 unit = 12 ounces [oz] or
             360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)

          -  Are participants who, in the opinion of the investigator, are in any way unsuitable to
             participate in the study

        Part 1 only:

        • Have any medical conditions, medical history or are taking any medication which are
        contraindicated within the lisinopril product information leaflet

        Part 2 only:

          -  Intend to use over-the-counter medication (with the exception of paracetamol and/or
             antacids) 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 of the investigational product

          -  Have any medical conditions, medical history or are taking any medication which are
             contraindicated within the metoprolol product information leaflet