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

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

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.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetic Nephropathy
• Intervention / Treatment: Drug: PF-03882845; Drug: PF-03882845; Drug: PF-03882845; Drug: Spironolactone; Other: placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • Pfizer Investigational Site
    • San Diego, California, United States, 92123
      • Pfizer Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • Pfizer Investigational Site
    • Miami, Florida, United States, 33169
      • Pfizer Investigational Site
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Pfizer Investigational Site
  • New York
    • New York, New York, United States, 10019
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: December 6, 2011
• First Submitted That Met QC Criteria: December 6, 2011
• First Posted (Estimate): December 8, 2011

Study Record Updates

• Last Update Posted (Estimate): October 29, 2013
• Last Update Submitted That Met QC Criteria: September 24, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus. albuminuria.
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: B0171011