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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01488877
First received: December 6, 2011
Last updated: September 24, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetic Nephropathy
Drug: PF-03882845
Drug: Spironolactone
Other: placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Serum Potassium at Day 8 [ Time Frame: Baseline, Day 7, 8 ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Serum Potassium at Day 15 [ Time Frame: Baseline, Day 14, 15 ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Confirmed and Severe Hyperkalemia [ Time Frame: Baseline up to Day 15 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Plasma Pharmacokinetic (PK) Parameters [ Time Frame: 0 (pre-dose), 2, 4, 6, 8, 10, 14, 24 hours post-dose on Day 1, 14 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15 [ Time Frame: Day 1 (Baseline), 15 ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Sitting Pulse Rate at Day 15 [ Time Frame: Day 1 (Baseline), 15 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 6
Study Start Date: January 2012
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Placebo Comparator: Placebo
Placebo once daily
Other: placebo
placebo once daily

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01488877

Locations
United States, California
Pfizer Investigational Site
Chula Vista, California, United States, 91911
Pfizer Investigational Site
San Diego, California, United States, 92123
United States, Florida
Pfizer Investigational Site
DeLand, Florida, United States, 32720
Pfizer Investigational Site
Miami, Florida, United States, 33169
United States, Michigan
Pfizer Investigational Site
Kalamazoo, Michigan, United States, 49007
United States, New York
Pfizer Investigational Site
New York, New York, United States, 10019
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01488877     History of Changes
Other Study ID Numbers: B0171011
Study First Received: December 6, 2011
Results First Received: July 18, 2013
Last Updated: September 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Type 2 diabetes mellitus. albuminuria.

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Kidney Diseases
Diabetes Complications
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Urologic Diseases
Spironolactone
Cardiovascular Agents
Diuretics
Diuretics, Potassium Sparing
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Mineralocorticoid Receptor Antagonists
Natriuretic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014