Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Sep 4;16(12):2614-2625.
doi: 10.1093/ckj/sfad213. eCollection 2023 Dec.

Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study

Daijo Inaguma  1 , Fumihiko Koiwa  2 , Masanori Tokumoto  3 , Masafumi Fukagawa  4 , Shinji Yoneda  5 , Hisami Yasuzawa  5 , Kenji Asano  6 , Keiko Hagita  6 , Yosuke Inagaki  6 , Daisuke Honda  7 , Tadao Akizawa  8
Affiliations

Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study

Daijo Inaguma et al. Clin Kidney J. .

Abstract

Background: Upacicalcet is a novel small-molecule calcimimetic agent developed for intravenous injection. Here, we evaluated the long-term efficacy and safety of upacicalcet treatment via intraindividual dose adjustment in haemodialysis patients with secondary hyperparathyroidism (SHPT).

Methods: A phase 2, multicentre, open-label, single-arm study was conducted. Upacicalcet was administered for 52 weeks; the starting dose was 50 μg thrice a week, and then adjusted to 25, 50, 100, 150, 200, 250, or 300 μg, according to the dose-adjustment method set in the protocol. The primary endpoint was the percentage of patients with serum intact parathyroid hormone (iPTH) level achieving a target range of 60-240 pg/mL (target achievement rate) at week 18.

Results: A total of 58 patients were administered upacicalcet. The target achievement rate of serum iPTH level at week 18 was 57.9%, which increased to 80.8% at week 52. The serum-corrected calcium (cCa) level decreased immediately after upacicalcet administration, but no further decrease was observed. Adverse events were observed in 94.8% of patients, and adverse drug reactions (ADRs) occurred in 20.7% of patients. The most common ADR was decreased adjusted calcium in eight patients; dizziness occurred as a serious ADR in one patient. The serum cCa level of patients who interrupted upacicalcet treatment at a serum cCa level of <7.5 mg/dL recovered to ≥7.5 mg/dL immediately after the interruption.

Conclusions: In haemodialysis patients with SHPT, upacicalcet doses of 25-300 μg for 52 weeks were found to be highly effective and well-tolerated, with minor safety concerns.

Keywords: calcimimetics; haemodialysis patients; parathyroid hormone; secondary hyperparathyroidism; upacicalcet.

PubMed Disclaimer

Conflict of interest statement

D.I. has received personal fees from SKK, Kyowa Kirin, Kissei Pharmaceutical, and Ono Pharmaceutical. F.K. has received personal fees from SKK, Kyowa Kirin, and Ono Pharmaceutical. M.T. has received personal fees from SKK, Kyowa Kirin, AstraZeneca, Torii Pharmaceutical, Astellas Pharma, Kissei Pharmaceutical, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Kowa, Bayer Yakuhin. M.F. has received personal fees from SKK, Kyowa Kirin, Bayer Japan, Kissei Pharmaceutical, Torii Pharmaceutical, Ono Pharmaceutical, and Astra Zeneca; grants from Kyowa Kirin and Ono Pharmaceutical. S.Y., H.Y., K.A., K.H., Y.I., and D.H. are employees of SKK. T.A. has received personal fees from SKK, Kyowa Kirin, Bayer, Astellas Pharma, GlaxoSmithKline, Japan Tobacco, Nipro, Torii Pharmaceutical, Kissei Pharmaceutical, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma, Ono Pharmaceutical, and Fuso Pharmaceutical Industries.

Figures

Graphical Abstract
Graphical Abstract
Figure 1:
Figure 1:
Study design. VDRAs, Vitamin D receptor activators.
Figure 2:
Figure 2:
Patient flow.
Figure 3:
Figure 3:
Time course of changes in the percentage of patients achieving the serum iPTH target range (60–240 pg/mL, as recommended by the Japanese Society for Dialysis Therapy guidelines). iPTH, intact parathyroid hormone.
Figure 4:
Figure 4:
Time course of changes in the serum iPTH (a), iPTH levels stratified at baseline (b), cCa (c), and P (d). Data are shown as median with interquartile range for iPTH (a and b), and mean with standard deviation for cCa (c) and P (d). cCa, corrected calcium; iPTH, intact parathyroid hormone; P, phosphate.
Figure 5:
Figure 5:
Time course of changes in serum levels of iFGF23 (a), serum BAP (b), serum total P1NP (c), and serum TRACP-5b (d). Data are shown as median with interquartile range. BAP, bone alkaline phosphatase; iFGF23, intact fibroblast growth factor 23; P1NP, N-terminal propeptide of type I procollagen; TRACP-5b, tartrate-resistant acid phosphatase-5b.
Figure 6:
Figure 6:
Time course of changes in upacicalcet dosing showing the percentage of all patients (a), those with baseline serum iPTH level ranging from 240–500 pg/mL (b), and those with baseline serum iPTH level >500 pg/mL (c). HD, haemodialysis; iPTH, intact parathyroid hormone.
Figure 7:
Figure 7:
Correlation between QT interval corrected using the Fridericia method (QTcF) and serum cCa levels (Treatment Periods 1 and 2). cCa, corrected calcium.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 2011;6:913–21. 10.2215/CJN.06040710 - DOI - PubMed
    1. Block GA, Klassen PS, Lazarus JM et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208–18. 10.1097/01.ASN.0000133041.27682.A2 - DOI - PubMed
    1. Jadoul M, Albert JM, Akiba T et al. Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2006;70:1358–66. 10.1038/sj.ki.5001754 - DOI - PubMed
    1. Fukuma S, Kurita N, Fukagawa M et al. Impact of Cinacalcet introduction on MBD management: the MBD-5D study in Japan. Kidney Int Suppl 2013;3:436–41. 10.1038/kisup.2013.91 - DOI - PMC - PubMed
    1. Akizawa T, Ikejiri K, Kondo Y et al. Evocalcet: a new oral calcimimetic for dialysis patients with secondary hyperparathyroidism. Ther Apher Dial 2020;24:248–57. 10.1111/1744-9987.13434 - DOI - PMC - PubMed