A Study To Evaluate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of PF-03882845 In Healthy Volunteers

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of PF-03882845 in Healthy Volunteers. To evaluate the pharmacokinetics of PF-03882845 in Healthy Volunteers. To evaluate the pharmacodynamics of PF-03882845 in Healthy Volunteers.

Official Title
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A Phase 1, Double-Blind (Sponsor Open), Randomized, Placebo- Controlled, Parallel Group, Oral Multiple-Dose Trial to Evaluate The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PF-03882845 in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: PF-03882845 or Placebo
* Drug: PF-03882845 or Placebo
* Drug: PF-03882845 or Placebo
* Drug: PF-03882845 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. Past medical history of epididymitis, orchitis, sexually transmitted diseases (chlamydia, gonorrhea, etc.) or urinary tract infection. History of prostatitis or prostate surgery. Urinary catheterization or instrumentation within 12 months of screening. Inguinal or scrotal hernia. Current or history of congenital genital abnormalities. Baseline scrotal ultrasound scan showing unilateral or bilateral scrotal blood flow abnormalities or anatomic abnormalities (hydrocele, cysts, other), with the exception of small epididymal cysts and spermatoceles. Any condition possibly affecting drug absorption (eg, gastrectomy). Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing. History of sensitivity to spironolactone, eplerenone, or related compounds. Serum potassium >5.5 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Healthy volunteers - PF-03882845 versus Placebo | Drug: PF-03882845 or Placebo<br>* PF-03882845 20 mg or Placebo, daily for 10 days.<br>|
| Experimental: Cohort 2<br>Healthy volunteers - PF-03882845 versus Placebo | Drug: PF-03882845 or Placebo<br>* PF-03882845 60 mg or Placebo, daily for 10 days.<br>|
| Experimental: Cohort 3<br>Healthy volunteers - PF-03882845 versus Placebo | Drug: PF-03882845 or Placebo<br>* PF-03882845 120 mg or Placebo, daily for 10 days.<br>|
| Experimental: Cohort 4<br>Healthy volunteers - PF-03882845 versus Placebo | Drug: PF-03882845 or Placebo<br>* PF-03882845 185 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 |
| --- | --- | --- |
| Single-Dose PK for PF-03382845: Cmax(ss), Tmax(ss), AUC(tau,ss), half life, Cmin(ss), Cave(ss), Ae%, CL/F, V/F, CL renal; accumulation ratios AUC(tau,ss)/AUC(tau,sd) and Cmax(ss)/Cmax(sd) |  | 13 days | 
| Safety and tolerability of PF-03382845 as determined by adverse event reporting, clinical laboratory results, vital signs (supine blood pressure and heart rate), physical examinations, electrocardiograms (ECGs) and potential sex hormone mediators. |  | 13 days | 

Secondary 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 PF-03882845 |  | 11 days | 
| Change from baseline(Day 0) to Day8 in exploratory mRNA gene expression biomarkers (SGK1:Sodium-and Serum/glucocorticoid regulated kinase 1 gene,ENaCα:Epithelial Sodium Channel alpha subunit,ENaCγ:Epithelial Sodium Channel gamma |  | 9 days | 
| subunit,MR: Mineral corticoid Receptor,ACTβ:Beta Actin) after administration of PF-03882845 or placebo.These results will not be included in the study report |  | 9 days |