PMID- 30254496
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220321
IS  - 1179-1438 (Print)
IS  - 1179-1438 (Electronic)
IS  - 1179-1438 (Linking)
VI  - 10
DP  - 2018
TI  - Pharmacokinetics of evocalcet in secondary hyperparathyroidism patients receiving 
      hemodialysis: first-in-patient clinical trial in Japan.
PG  - 101-111
LID - 10.2147/CPAA.S171044 [doi]
AB  - PURPOSE: Cinacalcet is a positive allosteric modulator of calcium-sensing 
      receptors in the parathyroid gland and an effective treatment for secondary 
      hyperparathyroidism. However, this agent has considerable side effects and dosage 
      limitations, which impair effective treatment. Therefore, we investigated the 
      pharmacokinetics, pharmacodynamics, and safety of the novel calcimimetic, 
      evocalcet. PATIENTS AND METHODS: This was a multicenter, open-label study of 
      single oral doses of 1, 4, and 12 mg evocalcet using an intrapatient dose 
      escalation protocol in 29 Japanese secondary hyperparathyroidism patients 
      receiving hemodialysis. Pharmacokinetics was assessed by plasma evocalcet 
      concentrations. Pharmacodynamic evaluations consisted of measuring intact 
      parathyroid hormone, serum corrected calcium, and fibroblast growth factor 23 
      concentrations. Safety and tolerability were evaluated by the analysis of adverse 
      events (AEs). RESULTS: After a single 1-, 4-, or 12-mg dose, plasma evocalcet 
      levels increased dose proportionally in a linear manner. Pharmacodynamic analyses 
      showed that evocalcet effectively reduced intact parathyroid hormone and serum 
      corrected calcium levels in a dose-dependent manner. AEs occurred in 31.0%, 
      28.6%, and 38.5% of patients receiving a single dose of 1, 4, or 12 mg, 
      respectively. Most AEs were mild in severity. CONCLUSION: Evocalcet is effective 
      in the short term, has linear pharmacokinetics, and is well tolerated as observed 
      by the low incidence of AEs.
FAU - Shigematsu, Takashi
AU  - Shigematsu T
AD  - Department of Nephrology, Wakayama Medical University, Wakayama, Japan, 
      taki@wakayama-med.ac.jp.
FAU - Shimazaki, Ryutaro
AU  - Shimazaki R
AD  - R&D Division, Kyowa Hakko Kirin Co., Ltd., Chiyoda-ku, Tokyo, Japan.
FAU - Fukagawa, Masafumi
AU  - Fukagawa M
AD  - Department of Internal Medicine, Division of Nephrology, Endocrinology and 
      Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
FAU - Akizawa, Tadao
AU  - Akizawa T
AD  - Department of Medicine, Division of Nephrology, Showa University School of 
      Medicine, Minato-ku, Tokyo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180911
PL  - New Zealand
TA  - Clin Pharmacol
JT  - Clinical pharmacology : advances and applications
JID - 101564865
PMC - PMC6141109
OTO - NOTNLM
OT  - Calcimimetics
OT  - evocalcet
OT  - hemodialysis
OT  - parathyroid hormone
OT  - secondary hyperparathyroidism
COIS- Disclosure TS has received consulting fees from KHK Co., Ltd., Ono Pharmaceutical 
      Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., and Fuji Pharma Co., Ltd., and 
      lecture fees from KHK Co., Ltd., Chugai Pharmaceutical Co., Ltd., Bayer Yakuhin, 
      Ltd., Kissei Pharmaceutical Co., Ltd., Torii Pharmaceutical Co., Ltd., and Ono 
      Pharmaceutical Co., Ltd. MF has received consulting fees from KHK Co., Ltd. and 
      Ono Pharmaceutical Co., Ltd., and lecture fees from KHK Co., Ltd., Bayer Yakuhin, 
      Ltd., Torii Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd., and 
      grants from KHK Co., Ltd. and Bayer Yakuhin, Ltd. TA has received consulting fees 
      from KHK Co., Ltd., Astellas Pharma Inc., Bayer Yakuhin, Ltd., Fuso 
      Pharmaceutical Industries, Ltd., Japan Tobacco Inc., Ono Pharmaceutical Co., 
      Ltd., and NIPRO Industry, and lecture fees from KHK Co., Ltd., Chugai 
      Pharmaceutical Co., Ltd., Bayer Yakuhin, Ltd., Kissei Pharmaceutical Co., Ltd., 
      Torii Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd. RS is employed 
      by KHK, which funded this research. The authors report no other conflicts of 
      interest in this work.
EDAT- 2018/09/27 06:00
MHDA- 2018/09/27 06:01
PMCR- 2018/09/11
CRDT- 2018/09/27 06:00
PHST- 2018/09/27 06:00 [entrez]
PHST- 2018/09/27 06:00 [pubmed]
PHST- 2018/09/27 06:01 [medline]
PHST- 2018/09/11 00:00 [pmc-release]
AID - cpaa-10-101 [pii]
AID - 10.2147/CPAA.S171044 [doi]
PST - epublish
SO  - Clin Pharmacol. 2018 Sep 11;10:101-111. doi: 10.2147/CPAA.S171044. eCollection 
      2018.