A Study of LY2623091 in Male and Females With Chronic Kidney Disease
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Intervention: LY2623091; Eplerenone
Intervention description: Administered orally; Administered orally
Intervention MeSH terms: Eplerenone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

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

Eligibility criteria:

        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