San Diego—In a study conducted among Japanese hemodialysis patients with hyperphosphatemia, PA 21 (sucroferric oxyhydroxide [SFOH]) showed a significant serum phosphorus reduction compared with sevelamer hydrochloride (HCI). That was among the findings of a randomized, open-label, parallel-group, multicenter, active-controlled phase 3 study reported during a poster session at Kidney Week 2015.
Fumihiko Koiwa, MD, PhD, and colleagues reported the study results in a poster titled Phase III Study to Investigate the Efficacy, Safety, and Tolerability of PA 21 (Sucroferrric Oxyhydroxide) Compared with Sevelamer Hydrochloride in Japanese Hemodialysis Patients with Hyperphosphatemia.
Hyperphosphatemia, a complication of advanced chronic kidney disease (CKD), is a risk factor for vascular calcification, cardiovascular events, and death. Hyperphosphatemia cannot be controlled via dietary restriction of phosphate intake and dialysis; most patients require treatment with oral phosphate binders. An ideal phosphate binder should effectively and specifically bind dietary phosphate regardless of intestinal pH, have minimal systemic absorption, have few side effects, and be associated with a low pill burden.
SFOH, a novel non-calcium based phosphate binder, is a mixture of polynuclear iron oxyhydroxide, sucrose, and starches. In a previous phase 3 study conducted at multiple sites in the United States, Europe, and other countries, the phosphorus-lowering effect of SFOH was shown to be non-inferior to sevelamer carbonate and superior to a non-effective dose of SFOH (250 mg/day).
In the Japanese study, doses of SFOH and sevelamer were titrated to maintain predefined serum phosphorous concentrations within the range recommended by the Japanese Society for Dialysis Therapy CKD-Mineral and Bone disorder guideline (3.5 to 6.0 mg/dL). The primary study objective was to establish the non-inferiority of SFOH to sevelamer HCI in Japanese patients with hyperphosphatemia; safety and tolerability were assessed at week 12.
Inclusion criteria were age ≥20 years, maintenance dialysis three times weekly for ≥12 weeks prior to the washout period, and predialysis serum concentrations >6.0 mg/dL and ≥10.0 mg/dL at the beginning of the week of the washout period. Exclusion criteria were serum concentration of ≤7.5 mg/dL, of >11.0 mg/dL at the beginning of the week of the washout period; intact-parathyroid hormone (PTH) concentration >800 pg/mL at the beginning of the week of the initiation of the washout period; a history of hemochromatosis or any other iron overload disorder, or serum ferritin >800 ng/mL or transferrin saturation (TSAT) >50% at the beginning of the week at the initiation of the washout period; or clinically significant gastrointestinal disorders based on the investigator’s diagnosis.
There were 321 subjects enrolled in the study; of those, 213 were randomized to receive either SFOH (n=108) or sevelamer HCI (n=105). Of the patients randomized, 94 in the SFOH group and 87 in the sevelamer HCI group completed the study.
At the end of the treatment period, mean adjusted concentrations of serum phosphorous were 5.00 mg/dL in the SFOH group compared with 5.34 mg/dL in the sevelamer group (between group difference, -0.34 mg/dL. These results confirmed the non-inferiority of SFOH to sevelamer. Further, the value was significantly lower in the SFOH group compared with the sevelamer group (an analysis of covariance with serum phosphorous concentrations at week 0 as a covariate; P=.02). The non-inferiority of SFOH to sevelamer was confirmed in both the per protocol set and the full analysis set.
In the SFOH group, the achievement rate of target serum phosphorous level between 3.5 and 6.0 mg/dl demonstrated good control. In addition, the mean number of tablets intake was lower in the SFOH group compared with the sevelamer group. Finally, changes in corrected serum calcium levels and serum intact-PTH levels were comparable in the two groups.
There were no significant differences in the incidence of adverse events or adverse drug reactions between the two groups. In the SFOH group, iron parameters such as serum ferritin, TSAT, and hemoglobin were prone to increase.
“The study met the non-inferiority primary end point. SFOH showed a significant serum phosphorous reduction in Japanese hemodialysis patients, compared with sevelamer (P=.02) and was associated with a lower pill burden (with less than one third tablets). SHOF represents a new treatment alternative for Japanese hemodialysis patients with hyperphosphatemia,” the researchers said.
Source: Koiwa F, Fukagawa M, Yokoyama K, Akizawa T, Terao A. Phase III study to investigate the efficacy, safety, and tolerability of PA21 (sucroferric oxyhydroxide) compared with sevelamer hydrochloride in Japanese hemodialysis patients with hyperphosphatemia. Abstract of a poster presented during American Society of Nephrology Kidney Week 2015, November 6, 2015, San Diego, California.