Abstract: FR-PO1071

Head-to-Head Efficacy and Safety Comparisons of a Novel Calcimimetic Agent (Evocalcet) with Cinacalcet in Japanese Hemodialysis Patients with Secondary Hyperparathyroidism: A Randomized Clinical Trial

Session Information

Category: Mineral Disease

  • 1202 Mineral Disease: Vitamin D, PTH, FGF-23

Authors

  • Fukagawa, Masafumi, Tokai University School of Medicine, Kanagawa, Japan
  • Shimazaki, Ryutaro, Kyowa Hakko Kirin Co., Ltd., Tokyo, Japan
  • Akizawa, Tadao, Showa University School of Medicine, Tokyo, Japan

Group or Team Name

  • the Evocalcet Study Group
Background

Cinacalcet is a potent calcimimetic agent used to treat secondary hyperparathyroidism (SHPT) in hemodialysis (HD) patients. Because there are many refractory patients who cannot tolerate cinacalcet owing to gastrointestinal (GI) symptoms, we developed evocalcet, a new oral calcimimetic agent. Here, we compared the efficacy and safety between evocalcet and cinacalcet in Japanese HD patients with SHPT.

Methods

This was a multicenter, randomized, double-blind, double-dummy, parallel-group, phase 3 trial. Evocalcet and cinacalcet were administered within the dose ranges of 1–8 mg/day and 12.5–100 mg/day, respectively. The primary efficacy endpoint was the non-inferiority of evocalcet to cinacalcet at achieving the target intact parathyroid hormone (iPTH) level of 60–240 pg/mL (target range in Japan) during weeks 28–30 (non-inferiority margin, 15% in the per protocol set (PPS)). For safety, adverse events (AEs) related to GI symptoms (abdominal discomfort, nausea, vomiting, abdominal distension, and decreased appetite) and serum calcium levels were evaluated.

Results

In total, 639 subjects were randomized. Among 519 patients in the PPS, the proportion of patients who achieved the target iPTH level was 72.7% (184/253) and 76.7% (204/266) in the evocalcet and cinacalcet groups, respectively. The estimated intergroup difference in the achievement rate was −4.0% (95% CI −11.4%, 3.5%, p=0.002 for non-inferiority). The proportion of patients who achieved a ≥30% reduction in iPTH level from baseline was comparable. GI AEs were observed in 18.6% (evocalcet) vs 32.8% (cinacalcet) of patients (difference −14.2% [95% CI −20.9%, −7.5%], p<0.001). The rates for decreased serum calcium level from baseline were comparable.

Conclusion

Non-inferiority of evocalcet to cinacalcet was verified in terms of PTH suppression, with a lower incidence of GI AEs in the evocalcet group. Our results suggest that evocalcet may be a potent alternative to existing calcimimetics with a wider safety margin for management of SHPT.

Funding

  • Commercial Support