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Trial record 85 of 112 for:    EPLERENONE

Multiple Dose Study of the Safety, Tolerability, Pharmacokinetics and Effect on Renal Potassium Clearance

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01237899
Recruitment Status : Completed
First Posted : November 10, 2010
Results First Posted : June 3, 2019
Last Update Posted : June 3, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Other
Condition Chronic Kidney Disease
Interventions Drug: LY2623091
Drug: Placebo
Drug: Eplerenone
Enrollment 32
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 1 mg LY2623091 First Then 25 mg LY2623091 1 mg LY2623091 First Then Placebo 1 mg LY2623091 First Then 50 mg Eplerenone 50 mg Eplerenone First Then 25 mg LY2623091 50 mg Eplerenone First Then Placebo Placebo First Then 25 mg LY2623091 10 mg LY2623091 First Then 0.3 mg LY2623091 10 mg LY2623091 First Then Placebo 10 mg LY2623091 First Then 50 mg Eplerenone 50 mg Eplerenone First Then 0.3 mg LY2623091 Placebo Then 0.3 mg LY2623091
Hide Arm/Group Description 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days. 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before 0.3 mg LY2623091 daily by mouth for 7 days. 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days. 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days. Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days.
Period Title: First Dosing Period
Started 1 3 4 3 2 4 1 3 4 3 4
Completed 1 3 4 3 2 4 1 3 4 3 4
Not Completed 0 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period of at Least 7 Days
Started 1 3 4 3 2 4 1 3 4 3 4
Completed 1 3 3 3 2 4 1 3 4 3 4
Not Completed 0 0 1 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             0             1             0             0             0             0             0             0             0             0
Period Title: Second Dosing Period
Started 1 3 3 3 2 4 1 3 4 3 4
Completed 1 3 3 3 2 4 1 3 4 3 4
Not Completed 0 0 0 0 0 0 0 0 0 0 0
Arm/Group Title 1 mg LY2623091 First Then 25 mg LY2623091 1 mg LY2623091 First Then Placebo 1 mg LY2623091 First Then 50 mg Eplerenone 50 mg Eplerenone First Then 25 mg LY2623091 50 mg Eplerenone First Then Placebo Placebo First Then 25 mg LY2623091 10 mg LY2623091 First Then 0.3 mg LY2623091 10 mg LY2623091 First Then Placebo 10 mg LY2623091 First Then 50 mg Eplerenone 50 mg Eplerenone First Then 0.3 mg LY2623091 Placebo Then 0.3 mg LY2623091 Total
Hide Arm/Group Description 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. 1 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days. 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 25 mg LY2623091 daily by mouth for 7 days. 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before 0.3 mg LY2623091 daily by mouth for 7 days. 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving placebo daily by mouth for 7 days. 10 mg LY2623091 daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 50 mg eplerenone daily by mouth for 7 days. 50 mg eplerenone daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days. Placebo daily by mouth for 7 days, followed by a minimum 7-day washout period before receiving 0.3 mg LY2623091 daily by mouth for 7 days. Total of all reporting groups
Overall Number of Baseline Participants 1 3 4 3 2 4 1 3 4 3 4 32
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants 3 participants 4 participants 3 participants 2 participants 4 participants 1 participants 3 participants 4 participants 3 participants 4 participants 32 participants
<=18 years 0 0 0 0 0 0 0 0 0 0 0 0
Between 18 and 65 years 1 3 4 3 2 4 1 3 4 3 4 32
>=65 years 0 0 0 0 0 0 0 0 0 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants 3 participants 4 participants 3 participants 2 participants 4 participants 1 participants 3 participants 4 participants 3 participants 4 participants 32 participants
Female 0 1 0 0 0 2 0 0 0 0 0 3
Male 1 2 4 3 2 2 1 3 4 3 4 29
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants 3 participants 4 participants 3 participants 2 participants 4 participants 1 participants 3 participants 4 participants 3 participants 4 participants 32 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
1
 100.0%
3
 100.0%
4
 100.0%
3
 100.0%
2
 100.0%
4
 100.0%
1
 100.0%
3
 100.0%
4
 100.0%
3
 100.0%
4
 100.0%
32
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1 participants 3 participants 4 participants 3 participants 2 participants 4 participants 1 participants 3 participants 4 participants 3 participants 4 participants 32 participants
Asian 0 1 0 0 0 0 0 1 0 0 0 2
White 1 2 4 3 2 4 1 2 4 3 4 30
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Netherlands Number Analyzed 1 participants 3 participants 4 participants 3 participants 2 participants 4 participants 1 participants 3 participants 4 participants 3 participants 4 participants 32 participants
1 3 4 3 2 4 1 3 4 3 4 32
1.Primary Outcome
Title Number of Participants With Clinically Significant Effects (Adverse Events)
Hide Description A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section.
Time Frame Baseline through 7 days for each treatment period
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug.
Arm/Group Title Placebo 0.3 mg LY2623091 1 mg LY2623091 10 mg LY2623091 25 mg LY2623091 50 mg Eplerenone
Hide Arm/Group Description:
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Overall Number of Participants Analyzed 16 8 8 8 8 15
Measure Type: Count of Participants
Unit of Measure: Participants
Serious Adverse Events
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Nonserious Adverse Events
6
  37.5%
2
  25.0%
5
  62.5%
4
  50.0%
6
  75.0%
9
  60.0%
2.Secondary Outcome
Title Pharmacodynamics: Serum to Urine Potassium Area Under the Concentration-Time Curve (AUC) Standardized for Urinary Excretion at Day 7
Hide Description A measure of the renal clearance of the potassium ion (K+). The Least Squares (LS) Mean value was adjusted for pre-challenge renal K+ clearance.
Time Frame Day 7: 24 Hour (hr), 48hr and 72hr Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable.
Arm/Group Title Placebo 0.3 mg LY2623091 1 mg LY2623091 10 mg LY2623091 25 mg LY2623091 50 mg Eplerenone
Hide Arm/Group Description:
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Overall Number of Participants Analyzed 16 8 8 7 6 15
Least Squares Mean (95% Confidence Interval)
Unit of Measure: liter per hour (L/h)
2.098
(1.930 to 2.281)
1.940
(1.748 to 2.153)
1.981
(1.781 to 2.204)
1.788
(1.602 to 1.995)
1.551
(1.383 to 1.739)
1.838
(1.687 to 2.002)
3.Secondary Outcome
Title Pharmacokinetics of LY2623091: Maximal Concentration (Cmax) at Day 6
Hide Description Cmax estimated for LY2623091.
Time Frame Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable.
Arm/Group Title 0.3 mg LY2623091 1 mg LY2623091 10 mg LY2623091 25 mg LY2623091
Hide Arm/Group Description:
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Overall Number of Participants Analyzed 8 8 8 8
Mean (Standard Deviation)
Unit of Measure: nanograms per milliliter (ng/mL)
7.57  (0.776) 27.5  (5.19) 324  (55.2) 812  (106)
4.Secondary Outcome
Title Pharmacokinetics LY2623091: Area Under the Concentration-Time Curve (AUC) at Day 6
Hide Description AUC from time 0, extrapolated to infinity, estimated for LY2623091.
Time Frame Day 6: Predose,1hr, 2hr, 3hr, 4hr, 8hr and 12 hr Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug and for whom the data are considered sufficient and interpretable.
Arm/Group Title 0.3 mg LY2623091 1 mg LY2623091 10 mg LY2623091 25 mg LY2623091
Hide Arm/Group Description:
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Daily by mouth for 7 days.
Overall Number of Participants Analyzed 8 8 8 8
Mean (Standard Deviation)
Unit of Measure: microgram*hour per milliliter (µg*h/mL)
0.123  (0.0141) 0.444  (0.0741) 5.50  (1.08) 13.7  (2.37)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo 0.3 mg LY2623091 1 mg LY2623091 10 mg LY2623091 25 mg LY2623091 50 mg Eplerenone
Hide Arm/Group Description Daily by mouth for 7 days. Daily by mouth for 7 days. Daily by mouth for 7 days. Daily by mouth for 7 days. Daily by mouth for 7 days. Daily by mouth for 7 days.
All-Cause Mortality
Placebo 0.3 mg LY2623091 1 mg LY2623091 10 mg LY2623091 25 mg LY2623091 50 mg Eplerenone
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo 0.3 mg LY2623091 1 mg LY2623091 10 mg LY2623091 25 mg LY2623091 50 mg Eplerenone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/16 (0.00%)      0/8 (0.00%)      0/8 (0.00%)      0/8 (0.00%)      0/8 (0.00%)      0/15 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo 0.3 mg LY2623091 1 mg LY2623091 10 mg LY2623091 25 mg LY2623091 50 mg Eplerenone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/16 (37.50%)      2/8 (25.00%)      5/8 (62.50%)      4/8 (50.00%)      6/8 (75.00%)      9/15 (60.00%)    
Cardiac disorders             
Palpitations  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/15 (6.67%)  1
Eye disorders             
Ocular hyperaemia  1  0/16 (0.00%)  0 0/8 (0.00%)  0 2/8 (25.00%)  2 0/8 (0.00%)  0 0/8 (0.00%)  0 0/15 (0.00%)  0
Gastrointestinal disorders             
Abdominal distension  1  0/16 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0 0/15 (0.00%)  0
Abdominal pain  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 2/8 (25.00%)  2 0/15 (0.00%)  0
Constipation  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0 0/15 (0.00%)  0
Diarrhoea  1  0/16 (0.00%)  0 1/8 (12.50%)  1 2/8 (25.00%)  2 0/8 (0.00%)  0 0/8 (0.00%)  0 1/15 (6.67%)  2
Flatulence  1  0/16 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 1/8 (12.50%)  1 0/8 (0.00%)  0 0/15 (0.00%)  0
Gingivitis  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/15 (0.00%)  0
Lip dry  1  1/16 (6.25%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/15 (0.00%)  0
Nausea  1  1/16 (6.25%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 2/8 (25.00%)  2 1/15 (6.67%)  1
Toothache  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0 0/15 (0.00%)  0
General disorders             
Application site irritation  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/15 (0.00%)  0
Catheter site related reaction  1  2/16 (12.50%)  3 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 2/8 (25.00%)  2 1/15 (6.67%)  1
Fatigue  1  1/16 (6.25%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 2/15 (13.33%)  2
Vessel puncture site reaction  1  0/16 (0.00%)  0 2/8 (25.00%)  2 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/15 (6.67%)  2
Infections and infestations             
Fungal skin infection  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/15 (6.67%)  1
Nasopharyngitis  1  2/16 (12.50%)  2 1/8 (12.50%)  1 1/8 (12.50%)  1 2/8 (25.00%)  2 2/8 (25.00%)  2 3/15 (20.00%)  3
Injury, poisoning and procedural complications             
Skin injury  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/15 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Arthralgia  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/15 (0.00%)  0
Myalgia  1  0/16 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 1/8 (12.50%)  1 0/8 (0.00%)  0 0/15 (0.00%)  0
Nervous system disorders             
Dizziness  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 2/8 (25.00%)  2 2/15 (13.33%)  2
Headache  1  0/16 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0 2/8 (25.00%)  2 5/15 (33.33%)  6
Renal and urinary disorders             
Pollakiuria  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/15 (6.67%)  1
Reproductive system and breast disorders             
Epididymitis  1  0/16 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0 0/15 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Cough  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0 0/15 (0.00%)  0
Dry throat  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0 0/15 (0.00%)  0
Nasal discomfort  1  0/16 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/8 (12.50%)  1 0/8 (0.00%)  0 0/15 (0.00%)  0
Oropharyngeal pain  1  1/16 (6.25%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/15 (6.67%)  1
Sneezing  1  1/16 (6.25%)  1 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 0/8 (0.00%)  0 1/15 (6.67%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01237899     History of Changes
Other Study ID Numbers: 14121
I4M-MC-MRAB ( Other Identifier: Eli Lilly )
First Submitted: November 8, 2010
First Posted: November 10, 2010
Results First Submitted: September 27, 2017
Results First Posted: June 3, 2019
Last Update Posted: June 3, 2019