A Study of LY2623091 in Male and Females With Chronic Kidney Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01427972
First received: August 31, 2011
Last updated: April 30, 2013
Last verified: March 2013
  Purpose

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


Condition Intervention Phase
Chronic Kidney Disease
Drug: LY2623091
Drug: Eplerenone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Study of the Safety and Efficacy of LY2623091 in Chronic Kidney Disease Patients

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change from baseline to 21 days in proteinuria based on 24 hours pooled urine [ Time Frame: Baseline, 21 Days of each treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline to 21 days in potassium clearance following an oral potassium challenge [ Time Frame: Baseline, 21 Days of each treatment period ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics: area under the concentration - time curve (AUC 0-24hr) of LY2623091 [ Time Frame: Predose up to 24 hours Postdose on Day 20 of each treatment period ] [ Designated as safety issue: No ]
  • Pharmacokinetic: maximum plasma concentration (Cmax) of LY2623091 [ Time Frame: Predose up to 24 hours Postdose on Day 20 of each treatment period ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: September 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 0.2 mg LY2623091
Daily by mouth for 21 days. Day 1 - 20 administered in the fed state. Day 21 administered in the fasted state. Minimum wash-out period of 28 days between dosing in treatment periods
Drug: LY2623091
Administered orally
Experimental: 1.5 mg LY2623091
Daily by mouth for 21 days. Day 1 - 20 administered in the fed state. Day 21 administered in the fasted state. Minimum wash-out period of 28 days between dosing in treatment periods
Drug: LY2623091
Administered orally
Experimental: 10 mg LY2623091
Daily by mouth for 21 days. Day 1 - 20 administered in the fed state. Day 21 administered in the fasted state. Minimum wash-out period of 28 days between dosing in treatment periods
Drug: LY2623091
Administered orally
Active Comparator: 50 mg Eplerenone
Daily by mouth for 21 days. Day 1 - 20 administered in the fed state. Day 21 administered in the fasted state. Minimum wash-out period of 28 days between dosing in treatment periods
Drug: Eplerenone
Administered orally

Detailed Description:

This trial consists of 4 treatment arms: 3 LY2623091 dose levels and eplerenone. Each patient 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. Patients will receive different treatments in periods 1 and 2. Patients 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 patients returning to the clinic for evaluations during each treatment period (Days 3 or 4, 7, and 14).

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    1. Male patients: Non-vasectomized male patients 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 patients: Female patients 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 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(ml/min/1.73m^2)
  • 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
  • Patients 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:

  • Patients 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. Patients 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
  • Patients 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
  • Patients receiving a renin inhibitor, or an Mineralocorticoid receptor (MR antagonist) must have a wash-out period of at least 1 month prior to randomization
  • Patients in whom dialysis or renal transplantation is anticipated by their physician within 6 months after the Screening
  • Patients with a history of acute kidney injury within 3 months before Screening
  • Patients 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
  • Patients with a diagnosis of Class three (III) or four (IV) congestive heart failure (as defined by the New York Heart Association)
  • Patients with evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies; patients with a history of cirrhosis or hepatitis C or are positive for hepatitis C antibody at Screening; patients who are known to be hepatitis B surface antigen-positive or are positive for hepatitis B surface antigen at Screening
  • Patients who are unwilling or unable to comply with the use of a data collection device to directly record data from the patient
  • Use of a metabolizing enzyme (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 in-patient 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 patients 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01427972

Locations
Bulgaria
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Sofia, Bulgaria, 1612
South Africa
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Bloemfontein, South Africa, 9300
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Newton Park, South Africa, 6045
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Pretoria, South Africa, 0184
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01427972     History of Changes
Other Study ID Numbers: 14350, I4M-MC-MRAC
Study First Received: August 31, 2011
Last Updated: April 30, 2013
Health Authority: South Africa: Department of Health

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency
Eplerenone
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014