Effects Of Eplerenone On Serum Aldesterone And Plasma Renin Activity

Study Overview
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Brief Summary
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To evaluate the changes in serum aldosterone and plasma renin activity on Day 0 and on Days 1 and 10 after administration of 100 mg of eplerenone daily for 10 days.

Official Title
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A Phase 1, Double-Blind (Sponsor Open), Randomized, Placebo-Controlled Trial To Evaluate The Effects Of 100 MG Once Daily Of Eplerenone On Serum Aldesterone And Plasma Renin Activity During 10 Days Of Dosing In Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Eplerenone or Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs) Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Evidence or history of clinically significant disease Subjects with a supine BP greater than or equal to 140 mm Hg systolic or greater than or equal to 90 mm Hg diastolic or <100 mm Hg systolic and <60 mm Hg diastolic on a single measurement, as described in the protocol Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing History of sensitivity to eplerenone, spironolactone or related compounds. Serum potassium >5.0 mEq/L at screening or Day 0

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Healthy Volunteers - eplerenone versus placebo. | Drug: Eplerenone or Placebo<br>* Eplerenone 100 mg or Placebo, daily for 10 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the effect curve (AUEC) for serum aldosterone and PRA on Day 0 and on Days 1 and 10 after administration of 100 mg of eplerenone |  | 11 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Single Dose PK for eplerenone: Cmax, Tmax, and AUCtau; Multiple Dose PK for eplerenone: Cmax(ss), Tmax(ss), AUC(,tau,ss), half life, Cmin(ss), Cave(ss), accumulation ratios AUC(tau,ss)/AUC(tau,sd) and Cmax(ss)/Cmax(sd). |  | 13 days | 
| Safety and tolerability of eplerenone as determined by adverse event reporting, clinical laboratory results, vital signs (supine blood pressure and heart rate), physical examinations and ECGs. |  | 13 days | 
| Change from baseline (Day 0) to Day 8 in exploratory mRNA gene expression biomarkers (SGK1: Serum/glucocorticoid regulated kinase 1 gene, ENaCα: Epithelial Sodium Channel alpha subunit, ENaCγ: Epithelial Sodium Channel gamma subunit, |  | 9 days | 
| MR: Mineralcorticoid Receptor, ACTβ: Beta Actin) after administration of eplerenone or placebo. These results will not be included in the study report. |  | 9 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eplerenone Aldosterone and Plasma Renin Activity responses Pharmacodynamics