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
Results First Received: July 18, 2013  
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
Condition: Type 2 Diabetic Nephropathy
Interventions: Drug: PF-03882845
Drug: Spironolactone
Other: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Total 6 participants were enrolled in the study. Study was terminated early after partial completion of Cohort 1 (PF-03882845 3 milligram (mg)/placebo) and Cohort 4 (spironolactone 25 mg/placebo); Cohort 2 (PF-03882845 1 or 10 mg/placebo) and Cohort 3 (PF-03882845 1, 10 or 30 mg/placebo) were not enrolled.

Reporting Groups
  Description
PF-03882845 Placebo Placebo matched to PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.
PF-03882845 3 mg PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.
Spironolactone Placebo Similar-looking placebo matched to spironolactone 25 mg tablet in Cohort 4, orally once daily up to Day 14.

Participant Flow for 2 periods

Period 1:   Initial Randomization
    PF-03882845 Placebo     PF-03882845 3 mg     Spironolactone Placebo  
STARTED     1     5     0  
COMPLETED     1     5     0  
NOT COMPLETED     0     0     0  

Period 2:   Re-randomization
    PF-03882845 Placebo     PF-03882845 3 mg     Spironolactone Placebo  
STARTED     0     0     3 [1]
COMPLETED     0     0     3  
NOT COMPLETED     0     0     0  
[1] Three participants were re-randomized from PF-03882845 3 mg arm.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Entire Study Population All participants who were enrolled in this study.

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
  6  
Age, Customized  
[units: participants]
 
less than (<) 18 years     0  
18 to 44 years     0  
45 to 64 years     6  
greater than or equal to (>=) 65 years     0  
Gender  
[units: participants]
 
Female     3  
Male     3  



  Outcome Measures
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1.  Primary:   Change From Baseline in Serum Potassium at Day 8   [ Time Frame: Baseline, Day 7, 8 ]

Measure Type Primary
Measure Title Change From Baseline in Serum Potassium at Day 8
Measure Description 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.
Time Frame Baseline, Day 7, 8  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Placebo Placebo matched to PF-03882845 3 mg tablet in Cohort 1 or similar-looking placebo matched to spironolactone 25 mg tablet in Cohort 4, orally once daily up to Day 14.
PF-03882845 3 mg PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.

Measured Values
    Placebo     PF-03882845 3 mg  
Number of Participants Analyzed  
[units: participants]
  4     5  
Change From Baseline in Serum Potassium at Day 8  
[units: milliequivalent/liter (mEq/L)]
Median ( Full Range )
   
Baseline     4.78  
  ( 4.2 to 5.0 )  
  4.90  
  ( 4.8 to 5.1 )  
Change at Day 8     0.20  
  ( -0.3 to 0.5 )  
  0.25  
  ( 0.2 to 0.7 )  

No statistical analysis provided for Change From Baseline in Serum Potassium at Day 8



2.  Primary:   Change From Baseline in Serum Potassium at Day 15   [ Time Frame: Baseline, Day 14, 15 ]

Measure Type Primary
Measure Title Change From Baseline in Serum Potassium at Day 15
Measure Description 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.
Time Frame Baseline, Day 14, 15  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Placebo Placebo matched to PF-03882845 3 mg tablet in Cohort 1 or similar-looking placebo matched to spironolactone 25 mg tablet in Cohort 4, orally once daily up to Day 14.
PF-03882845 3 mg PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.

Measured Values
    Placebo     PF-03882845 3 mg  
Number of Participants Analyzed  
[units: participants]
  4     5  
Change From Baseline in Serum Potassium at Day 15  
[units: mEq/L]
Median ( Full Range )
  0.40  
  ( -0.0 to 1.1 )  
  0.25  
  ( -0.2 to 0.9 )  

No statistical analysis provided for Change From Baseline in Serum Potassium at Day 15



3.  Primary:   Number of Participants With Confirmed and Severe Hyperkalemia   [ Time Frame: Baseline up to Day 15 ]

Measure Type Primary
Measure Title Number of Participants With Confirmed and Severe Hyperkalemia
Measure Description 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.
Time Frame Baseline up to Day 15  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Placebo Placebo matched to PF-03882845 3 mg tablet in Cohort 1 or similar-looking placebo matched to spironolactone 25 mg tablet in Cohort 4, orally once daily up to Day 14.
PF-03882845 3 mg PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.

Measured Values
    Placebo     PF-03882845 3 mg  
Number of Participants Analyzed  
[units: participants]
  4     5  
Number of Participants With Confirmed and Severe Hyperkalemia  
[units: participants]
   
Confirmed Hyperkalemia     2     5  
Severe Hyperkalemia     0     1  

No statistical analysis provided for Number of Participants With Confirmed and Severe Hyperkalemia



4.  Secondary:   Plasma Pharmacokinetic (PK) Parameters   [ Time Frame: 0 (pre-dose), 2, 4, 6, 8, 10, 14, 24 hours post-dose on Day 1, 14 ]

Measure Type Secondary
Measure Title Plasma Pharmacokinetic (PK) Parameters
Measure Description 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.
Time Frame 0 (pre-dose), 2, 4, 6, 8, 10, 14, 24 hours post-dose on Day 1, 14  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Data for all pre-specified PK parameters were not analyzed because a decision was made to prematurely terminate the study.

Reporting Groups
  Description
PF-03882845 3 mg PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.

Measured Values
    PF-03882845 3 mg  
Number of Participants Analyzed  
[units: participants]
  0  
Plasma Pharmacokinetic (PK) Parameters      

No statistical analysis provided for Plasma Pharmacokinetic (PK) Parameters



5.  Secondary:   Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15   [ Time Frame: Day 1 (Baseline), 15 ]

Measure Type Secondary
Measure Title Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15
Measure Description 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.
Time Frame Day 1 (Baseline), 15  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Placebo Placebo matched to PF-03882845 3 mg tablet in Cohort 1 or similar-looking placebo matched to spironolactone 25 mg tablet in Cohort 4, orally once daily up to Day 14.
PF-03882845 3 mg PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.

Measured Values
    Placebo     PF-03882845 3 mg  
Number of Participants Analyzed  
[units: participants]
  4     5  
Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15  
[units: millimeter of mercury (mmHg)]
Mean ± Standard Deviation
   
Baseline: Systolic BP     127.83  ± 19.601     125.53  ± 8.194  
Baseline: Diastolic BP     74.92  ± 10.049     74.13  ± 5.237  
Change at Day 15: Systolic BP     -4.83  ± 22.599     -3.20  ± 10.002  
Change at Day 15: Diastolic BP     -1.08  ± 9.398     1.00  ± 3.504  

No statistical analysis provided for Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15



6.  Secondary:   Change From Baseline in Sitting Pulse Rate at Day 15   [ Time Frame: Day 1 (Baseline), 15 ]

Measure Type Secondary
Measure Title Change From Baseline in Sitting Pulse Rate at Day 15
Measure Description 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.
Time Frame Day 1 (Baseline), 15  
Safety Issue Yes  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis set included all participants who received at least 1 dose of study medication.

Reporting Groups
  Description
Placebo Placebo matched to PF-03882845 3 mg tablet in Cohort 1 or similar-looking placebo matched to spironolactone 25 mg tablet in Cohort 4, orally once daily up to Day 14.
PF-03882845 3 mg PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.

Measured Values
    Placebo     PF-03882845 3 mg  
Number of Participants Analyzed  
[units: participants]
  4     5  
Change From Baseline in Sitting Pulse Rate at Day 15  
[units: beats per minute (bpm)]
Mean ± Standard Deviation
   
Baseline     65.25  ± 6.757     74.47  ± 12.844  
Change at Day 15     6.17  ± 6.495     -0.33  ± 8.788  

No statistical analysis provided for Change From Baseline in Sitting Pulse Rate at Day 15




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Study was terminated prematurely; this was based on a strategic decision by the sponsor to terminate further development of this compound for proposed indication. The study was not terminated for safety or lack of efficacy reasons.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


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