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Open Access 28-06-2022 | Hyperparathyroidism | Original Research Article

First-in-Patient Phase I/II Study of Upacicalcet in Japanese Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis: Pharmacokinetic and Pharmacodynamic Properties

Authors: Junichiro James Kazama, Fumihiko Koiwa, Keitaro Yokoyama, Masafumi Fukagawa, Kenji Asano, Daisuke Honda, Tadao Akizawa

Published in: Clinical Pharmacokinetics | Issue 9/2022

Abstract

Objective

Upacicalcet is a new renally excreted and injectable calcimimetic agent. We evaluated the pharmacokinetics, pharmacodynamics, safety, and tolerability of single and multiple intravenous administration of upacicalcet in patients with secondary hyperparathyroidism undergoing hemodialysis.

Methods

This study was a multicenter, randomized, placebo-controlled, double-blinded, dose-escalation study consisting of a single-dose study and a multiple-dose study. The single-dose study consisted of seven dose steps from 0.025 to 0.8 mg. For each step, six patients were randomly assigned 2:1 to receive upacicalcet or a placebo. The multiple-dose study occurred over 3 weeks in three-dose steps from 0.05 to 0.2 mg. For each step, 12 patients were randomly assigned 3:1 to receive upacicalcet or a placebo.

Results

The plasma concentration of upacicalcet increased in a dose-dependent manner and was maintained for the next dialysis. Upacicalcet was approximately 80% removed by a single dialysis and did not increase in the plasma concentration with repeated administration. Serum intact parathyroid hormone and corrected calcium (Ca²⁺) levels tended to decrease in response to the plasma concentration of upacicalcet. In the single-dose study, upper gastrointestinal symptoms were observed as a non-serious and mild adverse drug reaction in the groups receiving upacicalcet ≥ 0.4 mg. In the multiple-dose study, abdominal discomfort occurred in each patient in the 0.1 mg and 0.2 mg groups.

Conclusions

Upacicalcet for patients with secondary hyperparathyroidism undergoing hemodialysis could be a calcimimetic agent that acts in a dose-dependent manner and persistently until the next dialysis session. No safety or tolerability issues specific to upacicalcet were found.

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Title: First-in-Patient Phase I/II Study of Upacicalcet in Japanese Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis: Pharmacokinetic and Pharmacodynamic Properties
Authors: Junichiro James Kazama
Fumihiko Koiwa
Keitaro Yokoyama
Masafumi Fukagawa
Kenji Asano
Daisuke Honda
Tadao Akizawa
Publication date: 28-06-2022
Publisher: Springer International Publishing
Keywords: Hyperparathyroidism
Calcimimetic
Cinacalcet
Published in: Clinical Pharmacokinetics / Issue 9/2022
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-022-01139-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

First-in-Patient Phase I/II Study of Upacicalcet in Japanese Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis: Pharmacokinetic and Pharmacodynamic Properties

Abstract

Objective

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Methods

Results

Conclusions

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