Trial Outcomes & Findings for A Study To Evaluate The Safety And Tolerability Of PF-03882845 In Patients With Type 2 Diabetic Nephropathy (NCT NCT01488877)
NCT ID: NCT01488877
Last Updated: 2013-10-29
Results Overview
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.
TERMINATED
PHASE1
6 participants
Baseline, Day 7, 8
2013-10-29
Participant Flow
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.
Participant milestones
| Measure |
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.
|
|---|---|---|---|
|
Initial Randomization
STARTED
|
1
|
5
|
0
|
|
Initial Randomization
COMPLETED
|
1
|
5
|
0
|
|
Initial Randomization
NOT COMPLETED
|
0
|
0
|
0
|
|
Re-randomization
STARTED
|
0
|
0
|
3
|
|
Re-randomization
COMPLETED
|
0
|
0
|
3
|
|
Re-randomization
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study To Evaluate The Safety And Tolerability Of PF-03882845 In Patients With Type 2 Diabetic Nephropathy
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=6 Participants
All participants who were enrolled in this study.
|
|---|---|
|
Age, Customized
less than (<) 18 years
|
0 participants
n=5 Participants
|
|
Age, Customized
18 to 44 years
|
0 participants
n=5 Participants
|
|
Age, Customized
45 to 64 years
|
6 participants
n=5 Participants
|
|
Age, Customized
greater than or equal to (>=) 65 years
|
0 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Day 7, 8Population: Safety analysis set included all participants who received at least 1 dose of study medication.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
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
n=5 Participants
PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.
|
|---|---|---|
|
Change From Baseline in Serum Potassium at Day 8
Baseline
|
4.78 milliequivalent/liter (mEq/L)
Interval 4.2 to 5.0
|
4.90 milliequivalent/liter (mEq/L)
Interval 4.8 to 5.1
|
|
Change From Baseline in Serum Potassium at Day 8
Change at Day 8
|
0.20 milliequivalent/liter (mEq/L)
Interval -0.3 to 0.5
|
0.25 milliequivalent/liter (mEq/L)
Interval 0.2 to 0.7
|
PRIMARY outcome
Timeframe: Baseline, Day 14, 15Population: Safety analysis set included all participants who received at least 1 dose of study medication.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
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
n=5 Participants
PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.
|
|---|---|---|
|
Change From Baseline in Serum Potassium at Day 15
|
0.40 mEq/L
Interval 0.0 to 1.1
|
0.25 mEq/L
Interval -0.2 to 0.9
|
PRIMARY outcome
Timeframe: Baseline up to Day 15Population: Safety analysis set included all participants who received at least 1 dose of study medication.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
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
n=5 Participants
PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.
|
|---|---|---|
|
Number of Participants With Confirmed and Severe Hyperkalemia
Severe Hyperkalemia
|
0 participants
|
1 participants
|
|
Number of Participants With Confirmed and Severe Hyperkalemia
Confirmed Hyperkalemia
|
2 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 2, 4, 6, 8, 10, 14, 24 hours post-dose on Day 1, 14Population: Data for all pre-specified PK parameters were not analyzed because a decision was made to prematurely terminate the study.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 (Baseline), 15Population: Safety analysis set included all participants who received at least 1 dose of study medication.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
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
n=5 Participants
PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.
|
|---|---|---|
|
Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15
Baseline: Systolic BP
|
127.83 millimeter of mercury (mmHg)
Standard Deviation 19.601
|
125.53 millimeter of mercury (mmHg)
Standard Deviation 8.194
|
|
Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15
Baseline: Diastolic BP
|
74.92 millimeter of mercury (mmHg)
Standard Deviation 10.049
|
74.13 millimeter of mercury (mmHg)
Standard Deviation 5.237
|
|
Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15
Change at Day 15: Systolic BP
|
-4.83 millimeter of mercury (mmHg)
Standard Deviation 22.599
|
-3.20 millimeter of mercury (mmHg)
Standard Deviation 10.002
|
|
Change From Baseline in Sitting Systolic and Diastolic Blood Pressure at Day 15
Change at Day 15: Diastolic BP
|
-1.08 millimeter of mercury (mmHg)
Standard Deviation 9.398
|
1.00 millimeter of mercury (mmHg)
Standard Deviation 3.504
|
SECONDARY outcome
Timeframe: Day 1 (Baseline), 15Population: Safety analysis set included all participants who received at least 1 dose of study medication.
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.
Outcome measures
| Measure |
Placebo
n=4 Participants
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
n=5 Participants
PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.
|
|---|---|---|
|
Change From Baseline in Sitting Pulse Rate at Day 15
Baseline
|
65.25 beats per minute (bpm)
Standard Deviation 6.757
|
74.47 beats per minute (bpm)
Standard Deviation 12.844
|
|
Change From Baseline in Sitting Pulse Rate at Day 15
Change at Day 15
|
6.17 beats per minute (bpm)
Standard Deviation 6.495
|
-0.33 beats per minute (bpm)
Standard Deviation 8.788
|
Adverse Events
Placebo
PF-03882845 3 mg
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=4 participants at risk
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
n=5 participants at risk
PF-03882845 3 mg tablet in Cohort 1, orally once daily up to Day 14.
|
|---|---|---|
|
General disorders
Injection site injury
|
0.00%
0/4
|
20.0%
1/5
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
25.0%
1/4
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/4
|
20.0%
1/5
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
25.0%
1/4
|
0.00%
0/5
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
25.0%
1/4
|
0.00%
0/5
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER