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

Study of the Safety and Efficacy of LY2623091 in Chronic Kidney Disease Patients

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01427972
Enrollment
42
Registered
2011-09-02
Start date
2011-09-30
Completion date
2013-03-31
Last updated
2019-09-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Kidney Disease

Brief summary

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

Detailed description

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).

Interventions

DRUGLY2623091

Administered orally

DRUGEplerenone

Administered orally

Sponsors

Eli Lilly and Company
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Change From Baseline to Day 21 in Proteinuria Based on 24-hours Pooled UrineOver 24 hours at Baseline and on Day 21Proteinuria was the presence of excess serum protein in the urine. Proteinuria was calculated for each participant after each treatment period. Change was calculated as (Day 21 post-treatment value) minus (baseline value).

Secondary

MeasureTime frameDescription
Change From Baseline to Day 21 in Potassium Clearance Following an Oral Potassium ChallengeOver 0-6 hours at Baseline and on Day 21Urine potassium clearance is defined as the amount of renal potassium excreted per volume of urine from participant's pooled urine. The oral potassium challenge consisted of 35 milliequivalents (mEq) potassium administered over 10 minutes as a flavored potassium chloride solution. Change was calculated as (Day 21 values) minus (baseline values).
Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve During the Dosing Period of LY2623091 (AUC0-τ)Predose, 1, 2, 4, 8, 12, and 24 hours postdose on Day 20 of Treatment Periods 1 and 2—
PK: Maximum Plasma Concentration (Cmax) of LY2623091Predose, 1, 2, 4, 8, 12, and 24 hours postdose on Day 20 of Treatment Periods 1 and 2—

Other

MeasureTime frame
The Number of Participants Who Died While on StudyBaseline up to end of Treatment Period 2 plus 10-day follow-up (80 days)

Countries

Bulgaria, South Africa

Participant flow

Pre-assignment details

Participants (pts) were randomized to 1 of 4 arms, 3 LY2623091 (LY) and Eplerenone (Epl). Each participated in two 21-day treatment periods with washout period of at least 28 days. Pts who received LY in Period 1 were randomized to a different LY arm or Epl arm in Period 2. Pts who received Epl in Period 1 were randomized to an LY arm in Period 2.

Participants by arm

ArmCount
1.5 mg LY2623091 First Then 10 mg LY2623091
Participants received 1.5 milligram (mg) LY2623091 administered orally, once daily (QD) for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 10 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
3
1.5 mg LY2623091 First Then 50 mg Eplerenone
Participants received 1.5 mg LY2623091 administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 50 mg Eplerenone for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
4
1.5 mg LY2623091 First Then 0.2 mg LY2623091
Participants received 1.5 mg LY2623091 administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 0.2 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
4
50mg Eplerenone First Then 0.2 mg LY2623091
Participants received 50 mg Eplerenone administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 0.2 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
3
50mg Eplerenone First Then 1.5 mg LY2623091
Participants received 50 mg Eplerenone administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 1.5 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
4
50mg Eplerenone First Then 10 mg LY2623091
Participants received 50 mg Eplerenone administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 10 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
3
0.2 mg LY2623091 First Then 10 mg LY2623091
Participants received 0.2 mg LY2623091 administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 10 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
3
0.2 mg LY2623091 First Then 50 mg Eplerenone
Participants received 0.2 mg LY2623091 administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 50 mg Eplerenone for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
5
0.2 mg LY2623091 First Then 1.5 mg LY2623091
Participants received 0.2 mg LY2623091 administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 1.5 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
3
10mg LY2623091 First Then 50mg Eplerenone
Participants received 10 mg LY2623091 administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 50 mg Eplerenone for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
3
10mg LY2623091 First Then 0.2 mg LY2623091
Participants received 10 mg LY2623091 administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 0.2 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
3
10 mg LY2623091 First Then 1.5 mg LY2623091
Participants received 10 mg LY2623091 administered orally, QD for 21 days in treatment period 1 followed by a minimum 28-day washout period before receiving 1.5 mg LY2623091 for 21 days in treatment period 2. On Day 1 through Day 20, participants were in a fed state and on Day 21 participants were in a fasted state.
4
Total42

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007FG008FG009FG010FG011
Treatment Period 1 (21 Days)Protocol Violation000000010000
Treatment Period 2 (21 Days)Withdrawal by Subject010000000000
Washout (at Least 28 Days)Withdrawal by Subject000002000000

Baseline characteristics

Characteristic1.5 mg LY2623091 First Then 10 mg LY26230911.5 mg LY2623091 First Then 50 mg Eplerenone1.5 mg LY2623091 First Then 0.2 mg LY262309150mg Eplerenone First Then 0.2 mg LY262309150mg Eplerenone First Then 1.5 mg LY262309150mg Eplerenone First Then 10 mg LY26230910.2 mg LY2623091 First Then 10 mg LY26230910.2 mg LY2623091 First Then 50 mg Eplerenone0.2 mg LY2623091 First Then 1.5 mg LY262309110mg LY2623091 First Then 50mg Eplerenone10mg LY2623091 First Then 0.2 mg LY262309110 mg LY2623091 First Then 1.5 mg LY2623091Total
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants1 Participants0 Participants1 Participants0 Participants0 Participants1 Participants0 Participants1 Participants0 Participants1 Participants0 Participants5 Participants
Age, Categorical
Between 18 and 65 years
3 Participants3 Participants4 Participants2 Participants4 Participants3 Participants2 Participants5 Participants2 Participants3 Participants2 Participants4 Participants37 Participants
Race/Ethnicity, Customized
Black/African American
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants2 Participants1 Participants0 Participants0 Participants4 Participants
Race/Ethnicity, Customized
Caucasian
3 Participants2 Participants4 Participants3 Participants3 Participants3 Participants3 Participants4 Participants1 Participants2 Participants3 Participants3 Participants34 Participants
Race/Ethnicity, Customized
Mixed
0 Participants2 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants4 Participants
Region of Enrollment
Bulgaria
2 Participants2 Participants2 Participants2 Participants2 Participants1 Participants1 Participants3 Participants0 Participants1 Participants1 Participants3 Participants20 Participants
Region of Enrollment
Macedonia
0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
Region of Enrollment
South Africa
1 Participants2 Participants1 Participants1 Participants2 Participants2 Participants2 Participants2 Participants3 Participants2 Participants2 Participants1 Participants21 Participants
Sex: Female, Male
Female
2 Participants2 Participants0 Participants0 Participants2 Participants2 Participants1 Participants3 Participants2 Participants0 Participants1 Participants2 Participants17 Participants
Sex: Female, Male
Male
1 Participants2 Participants4 Participants3 Participants2 Participants1 Participants2 Participants2 Participants1 Participants3 Participants2 Participants2 Participants25 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —
other
Total, other adverse events
9 / 218 / 228 / 1710 / 21
serious
Total, serious adverse events
0 / 211 / 220 / 171 / 21

Outcome results

Primary

Change From Baseline to Day 21 in Proteinuria Based on 24-hours Pooled Urine

Proteinuria was the presence of excess serum protein in the urine. Proteinuria was calculated for each participant after each treatment period. Change was calculated as (Day 21 post-treatment value) minus (baseline value).

Time frame: Over 24 hours at Baseline and on Day 21

Population: All participants who received any study drug and had proteinuria values. Participants were analyzed based on the treatment they received.

ArmMeasureValue (MEAN)Dispersion
0.2 mg LY2623091Change From Baseline to Day 21 in Proteinuria Based on 24-hours Pooled Urine-98.9 milligrams/24 hours (mg/24 h)Standard Deviation 1450.56
1.5 mg LY2623091Change From Baseline to Day 21 in Proteinuria Based on 24-hours Pooled Urine-19.7 milligrams/24 hours (mg/24 h)Standard Deviation 876.85
10 mg LY2623091Change From Baseline to Day 21 in Proteinuria Based on 24-hours Pooled Urine119.4 milligrams/24 hours (mg/24 h)Standard Deviation 1923.11
50 mg EplerenoneChange From Baseline to Day 21 in Proteinuria Based on 24-hours Pooled Urine273.7 milligrams/24 hours (mg/24 h)Standard Deviation 1280.34
Secondary

Change From Baseline to Day 21 in Potassium Clearance Following an Oral Potassium Challenge

Urine potassium clearance is defined as the amount of renal potassium excreted per volume of urine from participant's pooled urine. The oral potassium challenge consisted of 35 milliequivalents (mEq) potassium administered over 10 minutes as a flavored potassium chloride solution. Change was calculated as (Day 21 values) minus (baseline values).

Time frame: Over 0-6 hours at Baseline and on Day 21

Population: All participants who received any study drug and had potassium clearance values. Participants were analyzed based on the treatment they received.

ArmMeasureValue (MEAN)Dispersion
0.2 mg LY2623091Change From Baseline to Day 21 in Potassium Clearance Following an Oral Potassium Challenge0.097 Hour*millimoles per liter (h*mmol/L)Standard Deviation 0.263
1.5 mg LY2623091Change From Baseline to Day 21 in Potassium Clearance Following an Oral Potassium Challenge-0.122 Hour*millimoles per liter (h*mmol/L)Standard Deviation 0.393
10 mg LY2623091Change From Baseline to Day 21 in Potassium Clearance Following an Oral Potassium Challenge-0.174 Hour*millimoles per liter (h*mmol/L)Standard Deviation 0.243
50 mg EplerenoneChange From Baseline to Day 21 in Potassium Clearance Following an Oral Potassium Challenge-0.019 Hour*millimoles per liter (h*mmol/L)Standard Deviation 0.245
Secondary

Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve During the Dosing Period of LY2623091 (AUC0-τ)

Time frame: Predose, 1, 2, 4, 8, 12, and 24 hours postdose on Day 20 of Treatment Periods 1 and 2

Population: All participants who received LY2623091 and had AUC0-τ values. Participants were analyzed based on the treatment they received.

ArmMeasureValue (MEAN)Dispersion
0.2 mg LY2623091Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve During the Dosing Period of LY2623091 (AUC0-τ)75.321 hours*nanogram/milliliter (h*ng/mL)Standard Deviation 31.927
1.5 mg LY2623091Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve During the Dosing Period of LY2623091 (AUC0-τ)526.640 hours*nanogram/milliliter (h*ng/mL)Standard Deviation 177.834
10 mg LY2623091Pharmacokinetics (PK): Area Under the Plasma Concentration Time Curve During the Dosing Period of LY2623091 (AUC0-τ)3096.658 hours*nanogram/milliliter (h*ng/mL)Standard Deviation 1448.414
Secondary

PK: Maximum Plasma Concentration (Cmax) of LY2623091

Time frame: Predose, 1, 2, 4, 8, 12, and 24 hours postdose on Day 20 of Treatment Periods 1 and 2

Population: All participants who received LY2623091and had Cmax values. Participants were analyzed based on the treatment they received.

ArmMeasureValue (MEAN)Dispersion
0.2 mg LY2623091PK: Maximum Plasma Concentration (Cmax) of LY26230914.540 nanograms/milliliter (ng/mL)Standard Deviation 2.003
1.5 mg LY2623091PK: Maximum Plasma Concentration (Cmax) of LY262309131.722 nanograms/milliliter (ng/mL)Standard Deviation 10.325
10 mg LY2623091PK: Maximum Plasma Concentration (Cmax) of LY2623091187.441 nanograms/milliliter (ng/mL)Standard Deviation 87.858
Other Pre-specified

The Number of Participants Who Died While on Study

Time frame: Baseline up to end of Treatment Period 2 plus 10-day follow-up (80 days)

Population: All participants who received at least 1 dose of study drug.

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
0.2 mg LY2623091The Number of Participants Who Died While on Study0 Participants
1.5 mg LY2623091The Number of Participants Who Died While on Study1 Participants
10 mg LY2623091The Number of Participants Who Died While on Study0 Participants
50 mg EplerenoneThe Number of Participants Who Died While on Study0 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026