Effects Of Eplerenone On Serum Aldesterone And Plasma Renin Activity

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Eplerenone or Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33143
      • Pfizer Investigational Site
    • South Miami, Florida, United States, 33143
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

Publications and helpful links

General Publications

• Eudy RJ, Sahasrabudhe V, Sweeney K, Tugnait M, King-Ahmad A, Near K, Loria P, Banker ME, Piotrowski DW, Boustany-Kari CM. The use of plasma aldosterone and urinary sodium to potassium ratio as translatable quantitative biomarkers of mineralocorticoid receptor antagonism. J Transl Med. 2011 Oct 21;9:180. doi: 10.1186/1479-5876-9-180.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: October 5, 2009
• First Submitted That Met QC Criteria: October 5, 2009
• First Posted (Estimate): October 6, 2009

Study Record Updates

• Last Update Posted (Actual): December 22, 2020
• Last Update Submitted That Met QC Criteria: December 19, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Eplerenone Aldosterone and Plasma Renin Activity responses Pharmacodynamics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: A6141115