A randomized trial of JTT-751 versus sevelamer hydrochloride in patients on hemodialysis.

Abstract

BACKGROUND:

JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient.

METHODS:

In this Phase 3, multicenter, randomized, open-label, parallel-group study, we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis. A total of 230 patients with a serum phosphate ≥1.97 and <3.23 mmol/L were randomized to JTT-751 (dose adjusted between 1.5 and 6.0 g/day) or sevelamer hydrochloride (dose adjusted between 3.0 and 9.0 g/day) for 12 weeks. The primary outcome was change in serum phosphate from baseline to end of treatment. Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone (PTH). The changes in ferritin, transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes.

RESULTS:

Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group, establishing non-inferiority of JTT-751 compared with sevelamer (least squares mean, -0.03 mmol/L; 95% confidence interval, -0.13 to 0.07 mmol/L). Corrected serum calcium increased and PTH decreased from baseline within both groups; changes between groups were similar. Gastrointestinal disorders were the most common adverse events in both groups; the incidence of diarrhea was higher in the JTT-751 group, while constipation occurred frequently in the sevelamer group. Treatment with JTT-751 resulted in significant relative increases in serum ferritin and transferrin saturation.

CONCLUSIONS:

Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia. Differential adverse effects were observed; biochemical markers of iron status increased in patients treated with JTT-751.

TRIAL REGISTRATION NUMBER:

CTI-111433 (The Japan Pharmaceutical Information Center at: http//www.clinicaltrials.jp). Date of registration: 7 March 2011.

• Authors: Keitaro Yokoyama, Takashi Akiba, Masafumi Fukagawa, Masaaki Nakayama, Kenichi Sawada, Yuji Kumagai, Glenn M Chertow, Hideki Hirakata
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 29 Issue 5 Pg. 1053-60 (May 2014) ISSN: 1460-2385 [Electronic] England
• PMID: 24376274 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Ferric Compounds
• Parathyroid Hormone
• Polyamines
• ferric citrate
• Sevelamer

Topics

• Adult
• Chelating Agents (therapeutic use)
• Female
• Ferric Compounds (therapeutic use)
• Humans
• Hyperphosphatemia (diagnosis, drug therapy, etiology)
• Japan
• Kidney Failure, Chronic (complications, therapy)
• Male
• Middle Aged
• Parathyroid Hormone (blood)
• Polyamines (therapeutic use)
• Renal Dialysis
• Sevelamer
• Young Adult