Study of the Safety and Efficacy in Chronic Kidney Disease Patients

• Register: EUCTR
• Last refreshed on: 24 March 2014
• Main ID: EUCTR2012-000773-23-BG
• Date of registration: 20/03/2012
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company
• Public title: Study of the Safety and Efficacy in Chronic Kidney Disease Patients
• Scientific title: Study of the Safety and Efficacy of LY2623091 in Chronic Kidney Disease Patients - MRAC
• Date of first enrolment: 23/04/2012
• Target sample size: 48
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000773-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Positive control with Eplerenone If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Bulgaria, Macedonia, the former Yugoslav Republic of, South Africa

Contacts

• Name: Clinical Trial Information
• Affiliation: Eli Lilly and Company Ltd

• Name: Clinical Trial Information
• Affiliation: Eli Lilly and Company Ltd

Key inclusion & exclusion criteria

Inclusion criteria:
1] Men and women of non-childbearing potential as determined by medical history and PE.
[1a] male subjects: agree to use 2 medically accepted methods of contraception
[1b] female subjects: women not of child-bearing potential

[2] Have been diagnosed with CKD

3] Have an estimated glomerular filtration rate (eGFR) between 30-70 ml/min/1.73 m2

4] Have been taking an ACE inhibitor and/or ARB, for at least 3 months, and at a stable dose for =2 months prior to randomization

5] Stable use of BP medication and acceptable cuff BP

6] Have serum potassium =5.0 mEq/L (equivalent to mmol/L) at screening, and no more than 1 hospitalization due to hyperkalemia within 1 year

[7] Are 18-75 years old, inclusive

8] Have given written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24

Exclusion criteria:
Patients who are currently enrolled in, or have discontinued within the last 30 days or 5 half lives (whichever is longer) of the investigational drug from, a clinical trial involving an investigational drug or device or an off-label use of an approved drug

Patients who 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 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 visit.

Patients with a history of acute kidney injury within 3 months before the screening visit.

Patients who have or are expected to require systemic immunosuppression therapy within 30 days of the screening visit (except for inhalant steroids).

Patients who use oral or parenteral corticosteroids within 30 days of the screening visit.

Patients with a diagnosis of Class III or IV congestive heart failure

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 the screening visit; patients who are known to be hepatitis B surface antigen-positive or are positive for hepatitis B surface antigen at the screening visit.

Patients who use CYP3A4 inhibitors or inducers, potassium-sparing diuretic drugs, potassium supplements or systemic glucocorticoids within 7 days of study enrollment. Intermittent use of nonsteroidal antiinflammatory drugs (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.

Patients who have donated blood of more than 500 mL within the last 60 days prior to screening.

Patients who have an average weekly alcohol intake that exceeds 21 units per week or subjects unwilling to stop alcohol within 48 hours of entry into study and for the duration of the study

Patients who consume 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic kidney disease
MedDRA version: 14.1 Level: LLT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders

Intervention(s)

Product Name: Not yet available
Product Code: LY2623091
Pharmaceutical Form: Capsule
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: LY2623091
Other descriptive name: [5-[(E)-(3-fluoro-6H-benzo[c][2]benzoxepin-11-ylidene)methyl]-1-[(1R)-1-methyl- 2-morpholino-ethyl]benzimidazol-2-yl]urea (E)-N-(5-((E)-3-fluoro-6Hdibenzo[ b,e]oxepin-11-ylidenemethyl)-1-[(1R)-1-methyl-2-morpholino-4-yl-ethyl)- 1,3-dihydro-benzimidazol-2-ylidene)-urea
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0,2-

Trade Name: Inspra
Product Name: Inspra
Product Code: Eplerenone
Pharmaceutical Form: Capsule
INN or Proposed INN: Eplerenone
CAS Number: 107724-20-9
Current Sponsor code: EPL
Other descriptive name: EPLERENONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Product Name: Not yet available
Product Code: LY2623091
Pharmaceutical Form: Capsule
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: LY2623091
Other descriptive name: [5-[(E)-(3-fluoro-6H-benzo[c][2]benzoxepin-11-ylidene)methyl]-1-[(1R)-1-methyl- 2-morpholino-ethyl]benzimidazol-2-yl]urea (E)-N-(5-((E)-3-fluoro-6Hdibenzo[ b,e]oxepin-11-ylidenemethyl)-1-[(1R)-1-methyl-2-morpholino-4-yl-ethyl)- 1,3- dihydro-benzimidazol-2-ylidene)-urea
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1,5-

Product Name: Not yet available
Product Code: LY2623091
Pharmaceutical Form: Capsule
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: LY2623091
Other descriptive name: [5-[(E)-(3-fluoro-6H-benzo[c][2]benzoxepin-11-ylidene)methyl]-1-[(1R)-1-methyl- 2-morpholino-ethyl]benzimidazol-2-yl]urea (E)-N-(5-((E)-3-fluoro-6Hdibenzo[ b,e]oxepin-11-ylidenemethyl)-1-[(1R)-1-methyl-2-morpholino-4-yl-ethyl)- 1,3- dihydro-benzimidazol-2-ylidene)-urea
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: • Investigate the effect of LY2623091 on potassium clearance following an oral potassium challenge in CKD patients

• Investigate the safety and tolerability of LY2623091 in CKD patients

• Explore the PK profile of LY2623091 after multiple oral dosing in CKD patients

Main Objective: To investigate the effect of LY2623091 on change from baseline in proteinuria after 3 weeks of daily oral dosing in CKD patients.

Primary end point(s): Change from Baseline to 21 days in proteinurea based on 24 hours pooled urine

Timepoint(s) of evaluation of this end point: Baseline, 21 Days of each treatment period

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: endpoint Baseline, 21 Days of each treatment
Period

Predose up to 24 hours Postdose on
Day 20 of each treatment period

Predose up to 24 hours Postdose on
Day 20 of each treatment period

Secondary end point(s): Change from baseline to 21 days in
potassium clearance following an oral potassium challenge

Pharmacokinetics: area under the
concentration - time curve (AUC 0-24hr) of LY2623091

Pharmacokinetic: maximum plasma
concentration (Cmax) of LY2623091

Secondary ID(s)

I4M-MC-MRAC

Source(s) of Monetary Support

N/A