A Study of LY2189265 and Sitagliptin in Participants With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: LY2189265; Sitagliptin
Intervention description: Administered subcutaneously; Administered orally
Intervention MeSH terms: Sitagliptin Phosphate; Dulaglutide
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to study the effect of LY2189265 on how the body absorbs and
      processes a Type 2 Diabetes Mellitus (T2DM) drug (sitagliptin) and how sitagliptin affects
      LY2189265 when they are taken together.

      The duration of participation in this study is expected to be approximately 61 days. The
      study requires 2 clinic confinements (one of 2 nights and one of 19 nights duration).

      The study involves 3 injections, subcutaneous, of 1.5 milligrams (mg) LY2189265 and 18 daily
      doses of 100 mg sitagliptin tablets administered orally.
    

Eligibility criteria:

        Inclusion Criteria:

          -  are males or females, diagnosed with T2DM (Type 2 Diabetes Mellitus) for ≥3 months
             prior to screening

          -  male participants 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 participant sterilization

               -  true abstinence (which is in line with the participant's usual lifestyle choice;
                  withdrawal or calendar methods are not considered acceptable)

          -  female participants not of child-bearing potential (that is, are postmenopausal or
             permanently sterilized [such as, tubal occlusion, hysterectomy, bilateral
             salpingectomy]). Such participants 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) or at
             least 1 year of spontaneous amenorrhea, with follicle stimulating hormone (FSH) ≥40
             milli-international units/milliliter (mIU/mL)

          -  female participants 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
             participants must also test negative for pregnancy at the time of enrollment

          -  have a body mass index (BMI) of between 23.0 and 40.0 kilograms/meter squared
             (kg/m^2), inclusive, at the time of screening

          -  have T2DM controlled with diet and exercise alone, or are on a stable dose of
             metformin Immediate Release (IR) for at least 4 weeks prior to screening, or are on
             metformin Extended Release (ER) and are capable/willing to be switched onto metformin
             IR or washed out prior to the first dose of investigational product, or are on
             sulfonylureas, acarbose (or other disaccharidase inhibitors), thiazolidinediones, or
             meglitinides and are capable/willing to be washed out prior to the first dose of
             investigational product

          -  have a fasting blood glucose value at screening ≤15.3 millimoles/liter (mmol/L) (275
             milligrams/deciliter [mg/dL])

          -  have a glycosylated hemoglobin A1c (HbA1c) value at screening (or within 4 weeks prior
             to screening) of 6.5% to 10%

          -  have clinical laboratory test results within normal reference range for the population
             or within normal reference range for the investigator site, or results with acceptable
             deviations that are judged to be not clinically significant by the investigator.
             Abnormalities of serum glucose, serum lipids, urinary glucose, and urinary protein
             consistent with T2DM are acceptable.

          -  have creatinine clearance (CrCl) of greater than 50 milliliters/minute (mL/min) at
             screening estimated by the Cockcroft-Gault formula

          -  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 procedures

        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 to sitagliptin-related compounds or any components of either formulation

          -  are persons who have previously completed or withdrawn from this study or any other
             study investigating LY2189265 in the 3 months prior to screening or have received
             glucagon-like peptides or incretin mimetics in the 3 months prior to screening

          -  have taken insulin, chlorpropamide, or alpha-glucosidase inhibitors within 30 days
             prior to screening

          -  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 poorly controlled hypertension (systolic blood pressure [BP] >160 millimeters of
             mercury [mmHg] and/or diastolic BP >100 mmHg) and/or evidence of labile BP including
             symptomatic postural hypotension

          -  have a history or presence of respiratory, hepatic, renal, endocrine, 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 a history or presence of cardiovascular disorder (including myocardial
             infarction, cerebrovascular accident, venous thromboembolism, arrhythmia [judged by
             the investigator to be clinically significant], or angina) within the last year, have
             symptoms or signs of congestive heart failure, or are expected to require coronary
             artery bypass surgery or angioplasty

          -  have a history or presence of pancreatitis (history of chronic pancreatitis or
             idiopathic acute pancreatitis) or gastrointestinal disorder, for example relevant
             esophageal reflux or gall bladder disease, or any gastrointestinal disease which
             impacts gastric emptying (GE) (such as, gastric bypass surgery, pyloric stenosis, with
             the exception of appendectomy) or could be aggravated by GLP-1 analogs or dipeptidyl
             peptidase-4 (DPP-4) inhibitors. Participants with dyslipidemia, and participants who
             had cholecystolithiasis (removal of gall stones) and/or 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 any existing medical condition that might interfere with interpretation of the
             data, including a history of gastrointestinal surgery (with the exception of
             appendectomy performed more than 12 months ago), peptic ulceration, gastrointestinal
             bleeding, diabetic gastroparesis, ulcerative colitis, Crohn's disease, Irritable Bowel
             Syndrome (IBS), gastric bypass, or laparoscopic gastric banding

          -  show evidence of significant active neuropsychiatric disease

          -  have had 2 or more episodes of severe hypoglycemia within the last 6 months prior to
             screening

          -  have personal or family history of medullary thyroid cancer (MTC) or a genetic
             condition that predisposes to MTC

          -  regularly uses known drugs of abuse and/or show positive findings on urinary drug
             screening

          -  intend to start new concomitant medication during the study, including
             over-the-counter and herbal medication, regularly use drugs that directly reduce
             gastrointestinal motility and/or regularly use systemic corticosteroids by oral,
             intravenous, or intramuscular route, or potent, inhaled, or intranasal steroids known
             to have a high rate of systemic absorption

          -  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

          -  have donated blood of more than 500 milliliters (mL) within the last month prior to
             screening

          -  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 Day -3 of each period until after the last pharmacokinetic
             (PK) sample has been taken for that period, or to limit alcohol intake to a maximum of
             2 units/day on all other days from screening through to follow-up. (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)

          -  smoke more than 10 cigarettes (or equivalent in nicotine) per day, and are unwilling
             to refrain from smoking on the day of LY2189265/sitagliptin administration or are
             unable to abide by Clinical Research Unit (CRU) restrictions on other inpatient days

          -  are participants who, in the opinion of the investigator, are in any way unsuitable to
             participate in the study

          -  have any medical conditions, medical history or are taking any medication which are
             contraindicated