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

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01488877

Enrollment

Registered

2011-12-08

Start date

2012-01-31

Completion date

2012-07-31

Last updated

2013-10-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 2 Diabetic Nephropathy

Keywords

Type 2 diabetes mellitus. albuminuria.

Brief summary

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

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.

Interventions

DRUGPF-03882845

3 mg tablet once daily

DRUGSpironolactone

spironolactone 25 mg once daily

OTHERplacebo

placebo once daily

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Serum Potassium at Day 8	Baseline, Day 7, 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.
Change From Baseline in Serum Potassium at Day 15	Baseline, Day 14, 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.
Number of Participants With Confirmed and Severe Hyperkalemia	Baseline up to Day 15	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

Measure	Time frame	Description
Plasma Pharmacokinetic (PK) Parameters	0 (pre-dose), 2, 4, 6, 8, 10, 14, 24 hours post-dose on Day 1, 14	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	Day 1 (Baseline), 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.
Change From Baseline in Sitting Pulse Rate at Day 15	Day 1 (Baseline), 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.

Countries

United States

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
Entire Study Population All participants who were enrolled in this study.	6
Total	6

Baseline characteristics

Characteristic	Entire Study Population
Age, Customized 18 to 44 years	0 participants
Age, Customized 45 to 64 years	6 participants
Age, Customized greater than or equal to (>=) 65 years	0 participants
Age, Customized less than (<) 18 years	0 participants
Sex: Female, Male Female	3 Participants
Sex: Female, Male Male	3 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 4	2 / 5
serious Total, serious adverse events	0 / 4	0 / 5

Outcome results

Primary

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.

Time frame: Baseline, Day 14, 15