Efficacy and Safety of a Novel Nicotinamide Modified-Release Formulation in the Treatment of Refractory Hyperphosphatemia in Patients Receiving Hemodialysis-A Randomized Clinical Trial.

INTRODUCTION

Despite widespread use of phosphate binders (PBs), phosphate control is insufficient in many hemodialysis patients. Preliminary clinical observations suggest that nicotinamide may act synergistically with PBs to improve phosphate control.

METHODS

This multinational, randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of nicotinamide modified release (NAMR) in combination with oral PB in a large cohort of hemodialysis patients with abnormal serum phosphate concentration (>4.5 mg/dl) despite treatment with PB. Patients entered a proof-of-efficacy phase (12 weeks [W12]) in which adjustments of relevant comedication were not permitted, followed by a safety extension phase for up to 52 weeks. Here, we report the results of the first phase.

RESULTS

The intention-to-treat (ITT) population consisted of 539 patients in the NAMR and 183 patients in the placebo group. NAMR and placebo were orally administered once daily (250-1500 mg/d). Mean age of patients was 61.8 years, and 63.0% were men. In the confirmatory analysis that estimated the difference in serum phosphate concentration after 12 weeks, NAMR proved superior over placebo with a significant difference of -0.51 mg/dl (95% confidence interval [CI] -0.72, -0.29; P < 0.0001). This effect was associated with significantly lower intact parathyroid hormone (iPTH) values (NAMR: 292.4±300.4 pg/ml vs. placebo: 337.0±302.7 pg/ml; P = 0.04) and an improved calcification propensity (T50 time; NAMR: 23.8±97.1 minutes vs. placebo: 2.3±100.7 minutes; P = 0.02). Diarrhea and pruritus were more frequent in the NAMR group.

CONCLUSION

NAMR combined with oral PB significantly improved phosphate control in hemodialysis patients.