The purpose of this trial is to investigate the safety and efficacy of LY2623091 in males and females with chronic kidney disease.

This trial consists of 4 treatment arms: 3 LY2623091 dose levels and eplerenone. Each participant will participate in 2 treatment periods, with a minimum wash-out period of 28 days between dosing in the 2 treatment periods. Dosing days will be numbered 1-21 in each of the 2 treatment periods. Participants will receive different treatments in periods 1 and 2. Participants will be housed as inpatients during the days of the controlled diet administration and the oral potassium challenge and until at least 24 hours after its completion (Days -3 to 1; Days 19 to 22, in each treatment period). Otherwise the study will be done on an outpatient basis, with participants returning to the clinic for evaluations during each treatment period (Days 3 or 4, 7, and 14).

Inclusion Criteria:

• Men and women of non-childbearing potential as determined by medical history and physical examination

  1. Male participants: Non-vasectomized male participants 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. Medically accepted effective forms of contraception may include condoms with contraceptive foam or having partners use diaphragms with contraceptive jelly or cervical caps with contraceptive jelly
  2. Female participants: Female participants must be of non-childbearing potential due to surgical sterilization (hysterectomy, bilateral oophorectomy or tubal ligation) or menopause. Postmenopausal women should be a minimum of 12 months without a menstrual period. Perimenopausal women who are 6 months without a menstrual period, have a follicle stimulating hormone (FSH) level 23.0-116.3 international unit/liter (IU/L) and are between the ages of 45 and 65 years, inclusive, are also eligible

• Have been diagnosed with Chronic Kidney Disease (CKD) (and including diabetic kidney disease and chronic glomerulonephritis)

• Have an estimated glomerular filtration rate (eGFR) between 30-70 milliliter/minute/1.73 square meters(30-70 ml/min/1.73m²)

• Have been taking an angiotensin converting enzyme (ACE) inhibitor and/or angiotensin II receptor blocker (ARB), for at least 3 months, and at a stable dose for greater than or equal to (≥) 2 months prior to randomization, and agree to continue to take such throughout the duration of the study

• Participants must meet both of the following renal function criteria prior to qualifying for randomization:

  1. Have Screening first morning urine protein/creatinine ratio (PCR) ≥400 milligram/gram (mg/g)
  2. Have stable renal function, in the opinion of the Investigator

• Stable use of blood pressure (BP) medication and acceptable cuff BP, as defined by the following criteria:

  1. While receiving stable dose of an ACE inhibitor and/or ARB
  2. While receiving stable doses of any other applicable BP medication (including diuretic therapy) for ≥3 weeks prior to screening
  3. Have seated cuff systolic BP less than or equal to (≤) 160 millimeters of mercury (mm Hg) and diastolic BP ≤100 mm Hg

• Have serum potassium (K+)≤5.0 milliequivalents/liter (mEq/L) at Screening, and no more that 1 hospitalization due to hyperkalemia within 1 year

• Are reliable and willing to make themselves available for the duration of the study and are willing to follow specific study procedures

• Have venous access sufficient to allow blood sampling

• Have lab values and other safety parameters that are, in the opinion of the investigator, acceptable for participation in the study

Exclusion Criteria:

• Participants who are currently enrolled in, or have discontinued within the last 30 days of the investigational drug from, a clinical trial involving an investigational drug or device or an off-label use of an approved drug (other than the study drug used in this study), or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participants may be enrolled in this study and dosed on day 31 or greater following the last day of previous investigational drug administration
• Have previously completed or withdrawn from this study or any other study investigating LY2623091
• Participants who are taking any diuretic drug and not receiving a stable dose for 3 weeks prior to the screening/qualification visit and through end of treatment
• Participants receiving a renin inhibitor, or an mineralocorticoid receptor (MR) antagonist must have a wash-out period of at least 1 month prior to randomization
• Participants in whom dialysis or renal transplantation is anticipated by their physician within 6 months after the Screening
• Participants with a history of acute kidney injury within 3 months before Screening
• Participants who have or are expected to require systemic immunosuppression therapy within 30 days of Screening(except for inhalant steroids)
• Use of oral or parenteral corticosteroids within 30 days of the Screening
• Participants with a diagnosis of Class three (III) or four (IV) congestive heart failure (CHF) [as defined by the New York Heart Association (NYHA)]
• Participants with evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies; participants with a history of cirrhosis or hepatitis C or are positive for hepatitis C antibody at Screening; participants who are known to be hepatitis B surface antigen-positive or are positive for hepatitis B surface antigen at Screening
• Participants who are unwilling or unable to comply with the use of a data collection device to directly record data from the participants
• Use of a metabolizing enzyme [cytochrome P450 (CYP3A4)] inhibitors or inducers, potassium sparing diuretic drugs (all other diuretic drugs are allowed, potassium supplements or systemic glucocorticoids within 7 days of study enrollment. Intermittent use of nonsteroidal anti-inflammatory drug (NSAIDs) is permitted, except for within 24 hours of critical urine sodium/potassium measures or during the inpatient periods, during which times NSAID use is limited to chronic use only (stable for ≥1 month prior to enrollment). Prostaglandin inhibitors should not be used during the inpatient periods of the study, with above exception of chronic NSAID use
• Have donated blood of more than 500 milliliter (mL) within the last 60 days of screening
• Have an average weekly alcohol intake that exceeds 21 units per week or participants unwilling to stop alcohol intake within 48 hours of entry into study and for the duration of the study [1 unit equal 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits]
• Evidence of regular use of drugs of abuse
• Consumption of natural licorice and/or natural licorice-containing products and/or regular daily consumption of grapefruit and/or grapefruit juice within 7 days of first dosing and/or anticipated consumption during the study

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

All randomized participants who received study drug.

Participants were randomized to 1 of 4 treatment arms, 3 LY2623091 (LY) and 1 Eplerenone (Epl). Each participated in 2 treatment periods and a washout period. Participants who received LY in Period 1 were randomized to a different LY arm or Epl arm in Period 2. Participants who received Epl in Period 1 were randomized to an LY arm in Period 2.