A Study To Evaluate The Safety And Tolerability Of PF-03882845 In Patients With Type 2 Diabetic Nephropathy

Study Overview
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Brief Summary
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PF-03882845 is a compound proposed for treatment of type 2 diabetic nephropathy. The primary purpose of this trial is to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of multiple doses of PF-03882845 in this population.

Detailed Description
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This study was terminated on 12-Sep-2012; this decision was made due to poor recruitment and overall business strategy. The study was not terminated for safety reasons nor for lack of efficacy.

Official Title
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A 2-week, Phase 1b, Randomized, Double-Blind, Placebo- Controlled, Multi-Dose, Dose-Escalating Study With PF-03882845 And One Dose Of Spironolactone To Evaluate Safety, Tolerability, Pharmacokinetics And Pharmacodynamics In Subjects With Type 2 Diabetes Mellitus And Albuminuria

Conditions
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Type 2 Diabetic Nephropathy

Intervention / Treatment
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* Drug: PF-03882845
* Drug: PF-03882845
* Drug: PF-03882845
* Drug: Spironolactone
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and/or Females between 18-65 years, inclusive. Body mass index of 18.5 to 45.4 kg/m2 at screening, inclusive. body weight equals or greater than 110 lb. Have type 2 diabetes mellitus. On stable dose of anti-diabetic and anti-hypertensive medication prior to screening. Exclusion Criteria: Recent evidence or medical history of unstable concurrent disease. Cardiovascular event within 3 months prior to screening. History of renal transplant. History of hospitalization for acute kidney injury or acute kidney dialysis within 6 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF03882845<br> | Drug: PF-03882845<br>* 3 mg tablet once daily<br>Drug: PF-03882845<br>* up to 10 mg tablet once daily<br>Drug: PF-03882845<br>* up to 30 mg once daily<br>|
| Active Comparator: Spironolactone<br>25 mg once daily | Drug: Spironolactone<br>* spironolactone 25 mg once daily<br>|
| Placebo Comparator: Placebo<br>Placebo once daily | Other: placebo<br>* placebo once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Potassium at Day 8 | Baseline value calculated as the average of -24 hours (pre-dose) measurement on Day -1 and 0 hours (immediately pre-dose) measurement on Day 1. Day 8 value calculated was average of 0 hours (immediately pre-dose) measurements on Day 7 and 8. Change from baseline values were presented under time point of Day 8. | Baseline, Day 7, 8 | 
| Change From Baseline in Serum Potassium at Day 15 | Baseline value calculated as the average of -24 hours (pre-dose) measurement on Day -1 and 0 hours (immediately pre-dose) measurement on Day 1. Day 15 value calculated was average of 0 hours (immediately pre-dose) measurement on Day 14 and measurement obtained prior to discharge on Day 15. Change from baseline values were presented under time point of Day 15. | Baseline, Day 14, 15 | 
| Number of Participants With Confirmed and Severe Hyperkalemia | Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated. Confirmed hyperkalemia is defined as serum potassium level greater than (>) upper limit of normal (ULN) of 5.4 mEq/L. Severe hyperkalemia is defined as serum potassium level >= 6.0 mEq/L. Number of participants with at least 1 confirmed or severe hyperkalemia is reported. | Baseline up to Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Pharmacokinetic (PK) Parameters | PK parameters were to be evaluated at Day 1 and Day 14 (steady state). Maximum observed plasma concentration (Cmax), time to reach maximum observed plasma concentration (Tmax), area under the curve from time zero to end of dosing interval (AUCtau) were to be evaluated at both Day 1 and Day 14 (steady state). Minimum observed plasma trough concentration (Cmin), average plasma concentration (Cavg), apparent oral clearance (CL/F), apparent volume of distribution (Vz/F) were to be evaluated only at Day 14 (steady state). Observed accumulation ratio (Rac) was also planned to be analyzed. | 0 (pre-dose), 2, 4, 6, 8, 10, 14, 24 hours post-dose on Day 1, 14 | 
| Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15 | Systolic blood pressure (BP): BP when heart is contracting; maximum arterial pressure during contraction of left ventricle of heart. Diastolic blood pressure: BP when heart is relaxing; minimum arterial pressure during relaxation and dilation of ventricles of heart. A total of 3 measurements were performed; average of triplicate BP values collected pre-dose on Day 1 served as baseline. The same arm and same sized cuff (properly sized and calibrated) was used throughout the study, after participant sat for 5 minutes for the first measurement and 2 minutes for second and third measurements. | Day 1 (Baseline), 15 | 
| Change From Baseline in Sitting Pulse Rate at Day 15 | Sitting pulse rate was measured in the brachial/radial artery for at least 30 seconds. A total of 3 measurements were performed; average of triplicate pulse rate values collected pre-dose on Day 1 served as baseline. | Day 1 (Baseline), 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus. albuminuria.