Evocalcet with vitamin D receptor activator treatment for secondary hyperparathyroidism

Takashi Shigematsu, Shinji Asada, Yuichi Endo, Takehisa Kawata, Masafumi Fukagawa, Tadao Akizawa, Takashi Shigematsu, Shinji Asada, Yuichi Endo, Takehisa Kawata, Masafumi Fukagawa, Tadao Akizawa

Abstract

This ad hoc analysis of a previously conducted phase 3 head-to-head comparison study of evocalcet and cinacalcet in secondary hyperparathyroidism patients undergoing maintenance hemodialysis evaluated the efficacy and safety of combined once-daily oral evocalcet and intravenous vitamin D receptor activator treatment stratified by weekly vitamin D receptor activator dose (117, 45, and 91 patients in no, low [< 1.5 μg], and high [≥ 1.5 μg] dose groups, respectively). Effects of vitamin D receptor activator were assessed on the basis of intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels; percent changes from baseline; proportions of patients who achieved target intact parathyroid hormone, corrected calcium, and phosphorus at Weeks 28-30; and adverse drug reactions. Intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels decreased in all groups; phosphorus and fibroblast growth factor-23 levels remained high in the high dose group. In the low and high dose groups, greater proportions of patients achieved the corrected calcium target compared with the no dose group (p = 0.043). Ratios of intact-to-C-terminal fibroblast growth factor-23 decreased in all groups. In low and high dose groups, hypocalcemia was less common than in the no dose group (p = 0.014). Evocalcet with concomitant vitamin D receptor activator demonstrated benefits such that more patients achieved the corrected calcium target and exhibited decreased fibroblast growth factor-23 synthesis; the incidence of hypocalcemia also decreased. Clinical trial registration: ClinicalTrials.gov (NCT02549391) and JAPIC (JapicCTI-153013).

Conflict of interest statement

TS received consulting fees from Kyowa Kirin Co., Ltd. (KKC), Ono Pharmaceutical, Taisho Toyama Pharmaceutical, Fuji Pharma, and FUSO, and lecture fees from KKC, Chugai Pharmaceutical, Bayer, Kissei Pharmaceutical, Torii Pharmaceutical, Ono Pharmaceutical, and FUSO. SA, YE, and TK are employees of KKC. MF received consulting fees from KKC and Ono Pharmaceutical; lecture fees from KKC, Bayer, Torii Pharmaceutical, and Ono Pharmaceutical; and grants from KKC and Bayer. TA received consulting fees from KKC, Astellas Pharma, Bayer, Fuso Pharmaceutical, Japan Tobacco, Ono Pharmaceutical, Sanwa Chemical, Otsuka, GSK, and NIPRO, and lecture fees from KKC, Chugai Pharmaceutical, Bayer, Kissei Pharmaceutical, Torii Pharmaceutical, and Ono Pharmaceutical. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1
Mean levels (left) and mean percent changes from baseline (right) in (A) intact PTH, (B) corrected calcium, (C) and phosphorus levels stratified by concomitant baseline IV VDRA weekly dose in patients with SHPT treated with evocalcet for 30 weeks. IV, intravenous; PTH, parathyroid hormone; SHPT, secondary hyperparathyroidism; VDRA, vitamin D receptor activator.
Fig 2
Fig 2
Mean levels of serum BAP (A) and TRACP-5b (B), stratified by concomitant baseline IV VDRA. BAP, bone specific alkaline phosphatase; IV, intravenous; SHPT, secondary hyperparathyroidism; TRACP-5b, tartrate-resistant acid phosphatase-5b; VDRA, vitamin D receptor activator.
Fig 3
Fig 3
Mean levels (left) and mean percent changes from baseline (right) in (A) intact FGF23 and (B) C-terminal FGF23 levels stratified by concomitant baseline IV VDRA weekly dose in patients with SHPT treated with evocalcet for 30 weeks. IV, intravenous; SHPT, secondary hyperparathyroidism; VDRA, vitamin D receptor activator. FGF23, fibroblast growth factor-23.
Fig 4. Intact FGF23-to-C-terminal FGF23 mean (standard…
Fig 4. Intact FGF23-to-C-terminal FGF23 mean (standard error) ratios, stratified by concomitant baseline IV VDRA.
FGF23, fibroblast growth factor-23; IV, intravenous; SHPT, secondary hyperparathyroidism; VDRA, vitamin D receptor activator.
Fig 5. Correlations between intact FGF23 and…
Fig 5. Correlations between intact FGF23 and C-terminal FGF23 at Week 0 and Week 30.
(A) all patients, (B), patients with no concomitant treatment of IV VDRA, (C) patients with IV VDRA

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