Clinical trial NCT00990223: Effects Of Eplerenone On Serum Aldesterone And Plasma Renin Activity
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Eplerenone Aldosterone and Plasma Renin Activity responses Pharmacodynamics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-10-06
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 11 days
Secondary outcomes:
measure: 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).
timeFrame: 13 days
measure: 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.
timeFrame: 13 days
measure: 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,
timeFrame: 9 days
measure: MR: Mineralcorticoid Receptor, ACTβ: Beta Actin) after administration of eplerenone or placebo. These results will not be included in the study report.
timeFrame: 9 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
city: South Miami
country: United States
facility: Pfizer Investigational Site
state: Florida
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.