Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics and Effect on Renal Potassium Clearance

The purpose of this study is to investigate the safety and tolerability of LY2623091 after multiple oral dosing in healthy men and women of non-childbearing potential. Two cohorts of 16 subjects will participate in 2 dosing periods. Treatment assignment will be double-blind for LY2623091 and placebo (negative control), and open label for eplerenone (positive control).


Eligibility Criteria:
Inclusion Criteria:

* Are healthy men and women of non-childbearing potential as determined by medical history and physical examination.

  * Male subjects: Non-vasectomized male subjects must agree to use 2 medically accepted methods of contraception with all sexual partners during the study and for 90 days following the final dosing.
  * Female subjects: Female subjects must be of non-childbearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy or tubal ligation) or menopause. They should be a minimum of 12 months without a menstrual period. Peri-menopausal women who are 6 months without a menstrual period.
* Have given written informed consent prior to any study-specific procedures.
* Are reliable and willing to make themselves available for the duration of the study and are willing to follow site-specific study procedures.
* Have a body mass index (BMI) of between 19 and 32.5 kilograms per square meter (kg/m\^2).
* Have clinical laboratory test results within the normal reference range for the population or study site, or test results with acceptable deviations that are judged by the Investigator not to be clinically significant.
* Have venous access sufficient to allow blood sampling per the protocol.
* Have serum potassium levels within the normal range.
* Are nonsmokers or smokers of less than or equal to 10 cigarettes per day.

Exclusion Criteria:

* Are currently enrolled in, or have discontinued, within 60 days inclusive, a clinical trial involving an investigational drug, device or an off-label use of an approved drug, or are concurrently enrolled in any other type of medical research judged to be scientifically or medically incompatible with this study. Subjects who meet any of these criteria may be enrolled in this study but they cannot be dosed until at least 60 days following the last day of the previous investigational trial.
* Have previously completed or withdrawn from this study or any other study investigating LY2623091.
* Have a history or presence of medical illness including but not limited to any cardiovascular, hepatic, respiratory, hematological, endocrine or neurological disease, or any clinically significant laboratory abnormality that is of a serious medical problem that would preclude study participation.
* Have an abnormality in the 12-lead electrocardiogram (ECG), which increases the risks associated with participation in the study.
* Are unwilling or unable to comply with the use of an electronic data capture system.
* Show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies, hepatitis C and/or positive hepatitis C antibody or hepatitis B and/or positive hepatitis B surface antigen.
* Use and/or intend to use any medication for a medical condition that is not compatible with Inclusion Criterion. For medications that may be used in "healthy" subjects (example given: preventative and/or naturopathic agents, temporary symptom-relieving medications, and so forth) the following constraints must be observed:

  * No use of vasoactive drugs (example given: diuretics, antihypertensive agents, phosphodiesterase inhibitors, erectile dysfunction medications, nasal decongestants, et cetera) or systemic glucocorticoids within 7 days of first dosing and/or anticipated use during the study.
  * No use of acetaminophen/paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) within 24 hours of first dosing and/or anticipated use during the study. Aspirin may not be used at doses greater than 100 milligrams per day (mg/day) within 7days of first dosing and/or anticipated use during the study.
  * No use of herbal or nutritional products within 7 days of first dosing and/or anticipated use during the study.
* Have donated blood of more than 50 milliliters (mL) within the last 60 days.
* Have an average weekly alcohol intake that exceeds 21 units per week and/or subjects unwilling to stop alcohol within 48 hours of study enrollment and for the duration of the study.
* Have an abnormally high blood pressure (supine or standing) defined as diastolic blood pressure greater than 95 millimeters of mercury (mmHg) and /or systolic blood pressure greater than 150 mmHg, confirmed by at least 1 repeat measurement.
* Have serum potassium greater than the upper limit of normal.
* Regularly use known drugs of abuse or show positive findings for such use on urinary drug screening.
* Consumption of natural licorice and/or natural licorice-containing products and/or grapefruit and/or grapefruit juice within 7 days of first dosing and/or anticipated consumption during the study.
* Consumption of methylxanthine-containing beverages and/or foods (example: coffee, tea, caffeinated soft drinks, chocolate) within 4 days of first dosing and/or anticipated consumption during the study.
* Are unwilling to abstain from salt-substitutes containing potassium for the duration of the study.