A Single Dose Study Of Antimineralocorticoid Activity Of PF-03882845 In Healthy Volunteers

Study Overview
=================
Brief Summary
-----------------
24-hr urinary sodium/potassium ratio will be a sensitive biomarker of antimineralocorticoid activity. The dose-response relationship of the antimineralocorticoid activity of PF-03882845 can be established following single oral doses.

Official Title
-----------------
A Phase 1, Double-Blind (Sponsor-Open), Placebo- And Active-Controlled, Single Dose, Crossover Study To Assess Antimineralocorticoid Activity Of Oral Pf-03882845 In Healthy Subjects.

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: 3 mg PF-03882845
* Drug: 10 mg PF-03882845
* Drug: 30 mg PF-03882845
* Drug: 100 mg PF-03882845
* Drug: Spironolactone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and/or female healthy volunteers, age 18 to 55 years. Females must be of non-childbearing potential. 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, diet restrictions and other trial procedures. Exclusion Criteria: Subjects with a supine BP >140 mm Hg systolic or >90 mm Hg diastolic or <100 mm Hg systolic or <60 mm Hg diastolic based on the average of the triplicate Serum potassium >=5.1 mmol/L or <3.5 mmol/L at screening, confirmed by a single repeat if deemed necessary. Estimated GFR <60 mL/min/1.73 m2 using the Cockcroft-Gault formula measurement of the individual parameters following at least 5 minutes of rest at Screening.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: 3 mg PF-03882845<br>* 3 mg PF-03882845, single oral dose<br>Drug: 10 mg PF-03882845<br>* 10 mg PF-03882845, single oral dose<br>Drug: 30 mg PF-03882845<br>* 30 mg PF-03882845, single oral dose<br>Drug: 100 mg PF-03882845<br>* 100 mg PF-03882845, single oral dose<br>Drug: Spironolactone<br>* 100 mg spironolactone, single oral dose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Twenty-four hour urinary Na/K ratio (AUC(0-24)). |  | 0-24hr postdose per period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve(AUClast) from the time of dosing to the last data point of PF-03882845. |  | 0-24 hr post dose per period | 
| Time of Maximum concentration(Tmax) of PF-03882845. |  | 0-24 hr post dose per period | 
| Maximum concentration (Cmax) of PF-03882845. |  | 0-24 hr post dose per period | 
| Safety and tolerability: Physical examinations, adverse event monitoring, clinical safety laboratory assessments, vital sign measurements and 12-lead ECGs. |  | 2 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Single dose, cross-over, active-control, placebo control, antimineralocorticoid activity