Published in:
Open Access
01-06-2022 | Calcimimetic | Original Research Article
First-in-Human Phase I Study of the Novel Injectable Calcimimetic Agent Upacicalcet in Healthy Adult Japanese Participants
Authors:
Fumihiko Koiwa, Rie Yazawa, Masafumi Fukagawa, Daisuke Honda, Tadao Akizawa
Published in:
Drugs in R&D
|
Issue 2/2022
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Abstract
Background and Objective
Upacicalcet sodium hydrate is a novel small-molecule calcimimetic and has potential as a therapeutic agent for secondary hyperparathyroidism. We assessed the pharmacokinetics, pharmacodynamics, safety, and tolerability of a single intravenous dose of upacicalcet in Japanese healthy adults.
Method
This was a single-center, double-blinded, randomized, placebo-controlled, dose-escalation study. For each cohort, eight subjects were randomly assigned at a ratio of 3:1 to receive a single injection of placebo or upacicalcet 0.01, 0.1, 1.0, or 2.5 mg.
Result
The plasma concentration of upacicalcet increased in a dose-dependent manner. Upacicalcet rapidly disappeared from plasma after administration. The half-life of upacicalcet was approximately 1–2 h. The major excretion route of upacicalcet was via urine. Serum intact parathyroid hormone decreased in accordance with the upacicalcet dose, from the lowest dose of 0.01 mg. Gastrointestinal disorders occurred in one patient in the 1.0 mg group and in five patients in the 2.5 mg group. All adverse events were nonserious, and no symptomatic hypocalcemia occurred.
Conclusion
This study showed that upacicalcet acted as a calcimimetic and was excreted in the urine unchanged with little metabolism. Moreover, upacicalcet is a small molecule and has a small volume of distribution. In addition, less than 50% of upacicalcet binds to human plasma proteins. These findings suggest that upacicalcet administered to patients undergoing hemodialysis might be expected to have a long excretion period and sustained pharmacological effect.