A Study of LY2409021 in Patients With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: LY2409021; Placebo
Intervention description: Administered Orally; Administered Orally
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 263.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Type 2 Diabetes Mellitus

Summary:

      LY2409021 is being evaluated for possible treatment in type 2 diabetes. This study is
      designed to compare LY2409021 given alone or given in combination with metformin against
      placebo the change in hemoglobin A1c after a 24-week treatment period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of Type 2 diabetes mellitus according to the World Health
             Organization (WHO) diagnostic criteria

          -  Are women not of child-bearing potential due to surgical sterilization (hysterectomy
             or bilateral oophorectomy or tubal ligation) or menopause.

          -  Are male patients using a reliable method of birth control during the study and until
             3 months after the last dose of study medication.

          -  Are being treated with either diet and exercise alone, or with diet and exercise in
             combination with metformin. Metformin therapy must have been stable and unchanged for
             at least 3 months prior to screening and at a dose of at least 1000 milligram per day
             (mg/day).

          -  Have a hemoglobin A1c (HbA1c) value of 7.0% to 10.5%, inclusive.

          -  Have a body mass index (BMI) between 25 to 45 kilogram per meter squared (kg/m^2),
             inclusive.

        In the opinion of the investigator, are capable and willing to:

          -  Perform self-monitoring of blood glucose

          -  Complete a study diary as required for this protocol

          -  Maintain consistent dietary, physical activity, and sleeping patterns throughout the
             duration of the study

          -  Comply with treatment regimens

          -  Have given written informed consent to participate in this study in accordance with
             local regulations and the Ethical Review Board (ERB) governing the study site.

        Exclusion Criteria:

          -  Have more than 1 episode of severe hypoglycemia (defined as an event during which the
             patient requires the assistance of another person to actively administer carbohydrate,
             glucagon, or other resuscitative actions) within 6 months prior to screening, or have
             a current diagnosis of hypoglycemia unawareness.

          -  Have had two or more emergency room visits or hospitalizations due to poor glucose
             control in the 6 months prior to screening.

          -  Have gastrointestinal disease that may significantly impact gastric emptying or
             motility or have undergone gastric bypass or gastric banding surgery.

          -  Have had a previous diagnosis of pancreatitis.

          -  Have New York Heart Association (NYHA) class II, III, or IV symptoms of heart failure

          -  Have a history of myocardial infarction, unstable angina, or a coronary
             revascularization procedure within 6 months of screening.

          -  Have a history of supraventricular tachycardia, ventricular tachycardia, or other
             cardiac arrhythmia.

          -  Have a history of transient ischemic attack (TIA) or stroke within 6 months of
             screening.

          -  Have poorly controlled hypertension (systolic blood pressure greater than or equal to
             150 mm Hg or diastolic blood pressure greater than or equal to 90 mm Hg) as determined
             by the mean of three separate measurements.

          -  Show evidence of labile blood pressure, including symptomatic postural hypotension.

          -  Have any abnormality of the ECG that would impact patient safety or data
             interpretation.

          -  Show clinical signs or symptoms of liver disease, or liver function tests (LFTs;
             aspartate aminotransferase [AST] or alanine aminotransferase [ALT]) greater than 2.5
             times upper limit of normal (ULN) as determined by the central laboratory at
             screening.

          -  Have a current or previous diagnosis of Gilbert's disease.

          -  Have previous or current diagnosis of Hepatitis B or C

          -  Have a serum creatinine >2 milligrams per deciliter (mg/dL) or, in patients being
             treated with metformin, a serum creatinine above (or creatinine clearance below) what
             is approved in the metformin product labeling in the respective country.

          -  Show evidence of uncorrected hypothyroidism or hyperthyroidism based on clinical
             evaluation and/or an abnormal thyroid stimulating hormone result as determined by the
             central laboratory at screening; patients receiving dose-stable thyroid replacement
             therapy for at least 3 months prior to screening will be allowed to participate in the
             study.

          -  Have any other abnormal laboratory value that, in the opinion of the investigator,
             precludes the patient from participation in the study. Laboratory abnormalities
             consistent with type 2 diabetes mellitus and all other eligibility criteria are
             acceptable: for example, abnormalities of blood glucose, hemoglobin A1c (HbA1c),
             urinary glucose, and urinary protein (with a range of trace to 1+ on dipstick).

          -  Have a currently suspected or treated malignancy, or are in remission from a
             clinically significant malignancy (other than basal or squamous cell skin cancer, in
             situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.

          -  Have a personal or family history of pancreatic neoplasia.

          -  Have non-fasting triglycerides >600 mg/dL.

          -  Use or have used insulin or GLP-1 agonists (for more than 1 week within the 3-month
             period prior to screening), or any oral antihyperglycemic medication (OAM) other than
             metformin within the 3-month period prior to screening.

          -  Currently use or intend to use prescription or over-the-counter medications, including
             herbal supplements, to promote weight loss or to regulate blood glucose.

          -  Have current chronic (>2 weeks) systemic glucocorticoid therapy (excluding ocular
             topical, other topical, inhaled preparations) or have received such therapy within 8
             weeks prior to screening.

          -  Currently use hyperglycemia-causing agents, hypoglycemia-causing agents (other than
             metformin), class II and III antiarrythmic agents, agents that reduce gastrointestinal
             motility, central nervous system stimulants (with the exception of caffeinated
             beverages), fibrates, and niacin greater than or equal to 1 grams per day (gm/day).

          -  Have an average weekly alcohol intake that exceeds 2 units per day for males and 1
             unit per day for females (1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150
             milliliters (mL) of wine; 1.5 oz or 45 milliliter (mL) of distilled spirits).

          -  Currently use drugs with a narrow therapeutic index (for example, digoxin, lithium,
             phenytoin, theophylline, and warfarin).

          -  Currently use drugs that are known to prolong the QT interval.

          -  Currently use or intend to use potent inhibitors of CYP3A, which include but are not
             limited to atazanavir, indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole,
             ketoconazole, nefazodone, saquinavir, and telithromycin.

          -  Have previously completed or withdrawn from this study or any other study
             investigating LY2409021.

          -  Have known allergies to LY2409021 or related compounds.

          -  Are currently enrolled in, or discontinued within the last 30 days from, a clinical
             trial involving an investigational product or unapproved use of a drug or device, or
             concurrently enrolled in any other type of medical research judged not to be
             scientifically or medically compatible with this study

          -  Have any other condition such as alcohol abuse, drug abuse, or psychiatric disorder
             that may affect the ability to participate in the trial.