A Study of the Effect of Dulaglutide on How Body Handles Digoxin in Healthy Participants

The purpose of this study is to study how the body processes digoxin and the effect of dulaglutide on how digoxin is processed by the body. Information about any side effects that may occur will also be collected.

This study is for research purposes only and is not intended to treat any medical condition. This research study requires that a blood sample be obtained and stored for future research involving genetic analysis.


Eligibility Criteria:
Inclusion Criteria:

* Are overtly healthy males or females, as determined by medical history and physical examination
* 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, they 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 enrolment. 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 per 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 enrolment
* Have a body mass index (BMI) of 18.5 to 32.0 kilogram per square meter (kg/m\^2), inclusive, at 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 (potassium, magnesium, and calcium values must be within the normal range)
* Have normal renal function defined as an estimated creatinine clearance (CrCl) of ≥80 milliliter per minute (mL/min)
* Have venous access sufficient to allow for blood sampling
* 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 approved by Lilly and the ethical review board (ERB) governing the site

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 dulaglutide (LY2189265) or to digoxin, related compounds or any components of either formulation
* Are participants who have previously completed or withdrawn from this study or any other study investigating dulaglutide in the 3 months prior to screening or have received glucagon-like peptides or incretin mimetics in the 3 months prior to screening
* Have an abnormality in the 12-lead electrocardiogram (ECG) (such as, first, second, or third degree atrioventricular \[AV\] block, prolonged corrected QT \[QTc\] interval, sinus tachycardia, sinus bradycardia, atrial fibrillation, or sinus node disease) that, in the opinion of the investigator, increases the risks associated with participating in the study
* Have a history of significant dysrhythmias or AV block
* Have an abnormal blood pressure (after at least 5 minutes sitting) that, in the opinion of the investigator, increases the risks associated with participating in the study
* Have a history or presence of cardiac, respiratory, hepatic, renal, endocrine (such as, hypothyroidism), 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 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. 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
* Show evidence of significant active neuropsychiatric disease
* Have 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
* Are women with a positive pregnancy test or women who are lactating
* Have used or intend to use over-the-counter medication other than acetaminophen within 7 days prior to dosing or prescription medication (with the exception of vitamin/mineral supplements) within 14 days prior to dosing, or have used St John's Wort within 14 days prior to dosing
* Have donated blood of more than 500 mL within the month prior to screening
* Have an average weekly alcohol intake that exceeds 21 units per week (males) 14 units per week (females), or are unwilling to stop alcohol consumption from screening through 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)
* Are smokers
* Have a history of cancer with the past 20 years, with the exception of basal cell or squamous cell skin cancer, or treated cervical carcinoma in situ
* Intend to consume grapefruit within 7 days prior to dosing
* 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