nly those subjects randomized to treatment with Zerenex during the Safety Assessment Period were randomized in a 1:1 ratio to either continue treatment with Zerenex or switch to placebo for a 4-week treatment period. Subjects were titrated during the study to achieve serum phosphorus levels that ranged between 3.5 to 5.5 mg/dL.
The primary objectives of this study were to determine the long-term safety of KRX-0502 (ferric citrate) in subjects with ESRD undergoing either hemodialysis or peritoneal dialysis, and the efficacy of Zerenex following 52 weeks of treatment in a four-week, randomized, open-label, placebo-controlled Efficacy Assessment Period. Zerenex was administered using a 1 gram oral caplet formulation.
Oral iron therapy was not permitted during the course of the study. IV iron therapy was not permitted if a subject’s serum ferritin level was greater than 1,000 ng/mL or the transferrin saturation (TSAT) was greater than 30%. The use of ESAs was at the physician’s discretion.
Primary Efficacy Endpoint
The primary efficacy endpoint of this trial was the mean change in serum phosphorus from baseline (Week 52) to end of the four-week Efficacy Assessment Period (Week 56) versus placebo in the Intent-to-Treat (ITT) group. The ITT group included 183 subjects, representing all subjects who took at least one dose of Zerenex or placebo in the Efficacy Assessment Period and provided at least one post-baseline efficacy assessment.
Zerenex met the primary efficacy endpoint with a highly statistically significant result (p<0.0001).
|
Mean Serum Phosphorus (mg/dL) |
Placebo(n=91) |
Zerenex(n=92) |
|
Baseline (Week 52) |
5.3 |
5.2 |
|
End of Treatment1 (Week 56) |
7.2 |
4.9 |
|
Change from Baseline at Week 56 |
1.9 |
-0.3 |
|
Least Squares (LS) Mean Difference from Placebo2p-value2 |
|
-2.3p<0.0001 |
1 Last observation carried forward was used for missing data.
2 The LS Mean treatment difference and p-value is created via an ANCOVA model with treatment as the fixed effect and baseline as the covariate.
Key Secondary Efficacy Endpoints Related to Serum Phosphorus
During the 52-week Safety Assessment Period, Zerenex maintained serum phosphorus in the normal range, with highly statistically significant changes in mean serum phosphorus concentration at Weeks 12, 24, 36, 48, and 52 as compared to baseline (Day 0).
|
n=277 |
Baseline |
Week |
|
12 |
24 |
36 |
48 |
52 |
|
Zerenex Mean SerumPhosphorus (mg/dL)1 |
7.4 |
5.4 |
5.2 |
5.2 |
5.3 |
5.3 |
|
Change from Baseline |
|
-2.0 |
-2.2 |
-2.2 |
-2.1 |
-2.1 |
|
% Change from Baseline |
|
-27.0% |
-29.7% |
-29.7% |
-28.4% |
-28.4% |
|
p-value |
|
<0.0001 |
<0.0001 |
<0.0001 |
<0.0001 |
<0.0 |
