Pharmacodynamics of evocalcet for secondary hyperparathyroidism in Japanese hemodialysis patients.
Adult
Aged
Calcimimetic Agents
/ administration & dosage
Calcium
/ blood
Drug Administration Schedule
Female
Fibroblast Growth Factor-23
Fibroblast Growth Factors
/ blood
Humans
Hyperparathyroidism, Secondary
/ blood
Japan
Male
Middle Aged
Naphthalenes
/ administration & dosage
Parathyroid Hormone
/ blood
Phosphorus
/ blood
Pyrrolidines
/ administration & dosage
Renal Dialysis
/ adverse effects
Renal Insufficiency, Chronic
/ blood
Treatment Outcome
Young Adult
Calcimimetics
Evocalcet
Hemodialysis
Parathyroid hormone
Pharmacodynamics
Secondary hyperparathyroidism
Journal
Clinical and experimental nephrology
ISSN: 1437-7799
Titre abrégé: Clin Exp Nephrol
Pays: Japan
ID NLM: 9709923
Informations de publication
Date de publication:
Feb 2019
Feb 2019
Historique:
received:
12
06
2018
accepted:
15
08
2018
pubmed:
31
8
2018
medline:
18
6
2019
entrez:
31
8
2018
Statut:
ppublish
Résumé
This study investigated the pharmacokinetics, pharmacodynamics, and safety of multiple doses of evocalcet in Japanese secondary hyperparathyroidism (SHPT) patients receiving hemodialysis. In this multicenter, open-label study, conducted between August 2013 and March 2014, 27 patients received multiple doses of 1 and 4 mg evocalcet for 14 days, followed by an extension period of multiple doses of 8 and 12 mg evocalcet for 7 days using an intra-patient dose escalation protocol. Pharmacodynamic parameters consisted of measurement of intact parathyroid hormone (PTH), serum-corrected calcium, serum phosphorus and intact fibroblast growth factor 23 concentrations. Safety was assessed by analysis of adverse events. Plasma evocalcet levels reached steady state 3 days after the first day of administration. Pharmacodynamic analyses showed that evocalcet effectively reduced intact PTH and serum-corrected calcium levels. Adverse events (AEs) occurred in 29.6 and 62.5% of patients receiving multiple doses of 1 or 4 mg, respectively. The AE 'blood calcium decreased' occurred in eight patients (33.0%) after multiple doses of 4 mg. All events were mild, except for one patient with a moderate AE (abnormal liver function) and one patient with a severe adverse drug reaction (blood calcium decreased). Multiple doses of evocalcet reduced intact PTH levels with a concomitant decrease in serum calcium levels. Evocalcet was well tolerated in SHPT patients receiving hemodialysis.
Sections du résumé
BACKGROUND
BACKGROUND
This study investigated the pharmacokinetics, pharmacodynamics, and safety of multiple doses of evocalcet in Japanese secondary hyperparathyroidism (SHPT) patients receiving hemodialysis.
METHODS
METHODS
In this multicenter, open-label study, conducted between August 2013 and March 2014, 27 patients received multiple doses of 1 and 4 mg evocalcet for 14 days, followed by an extension period of multiple doses of 8 and 12 mg evocalcet for 7 days using an intra-patient dose escalation protocol. Pharmacodynamic parameters consisted of measurement of intact parathyroid hormone (PTH), serum-corrected calcium, serum phosphorus and intact fibroblast growth factor 23 concentrations. Safety was assessed by analysis of adverse events.
RESULTS
RESULTS
Plasma evocalcet levels reached steady state 3 days after the first day of administration. Pharmacodynamic analyses showed that evocalcet effectively reduced intact PTH and serum-corrected calcium levels. Adverse events (AEs) occurred in 29.6 and 62.5% of patients receiving multiple doses of 1 or 4 mg, respectively. The AE 'blood calcium decreased' occurred in eight patients (33.0%) after multiple doses of 4 mg. All events were mild, except for one patient with a moderate AE (abnormal liver function) and one patient with a severe adverse drug reaction (blood calcium decreased).
CONCLUSION
CONCLUSIONS
Multiple doses of evocalcet reduced intact PTH levels with a concomitant decrease in serum calcium levels. Evocalcet was well tolerated in SHPT patients receiving hemodialysis.
Identifiants
pubmed: 30159688
doi: 10.1007/s10157-018-1635-6
pii: 10.1007/s10157-018-1635-6
pmc: PMC6510802
doi:
Substances chimiques
Calcimimetic Agents
0
Naphthalenes
0
PTH protein, human
0
Parathyroid Hormone
0
Pyrrolidines
0
Phosphorus
27YLU75U4W
Fibroblast Growth Factors
62031-54-3
Fibroblast Growth Factor-23
7Q7P4S7RRE
evocalcet
E58MLH082P
Calcium
SY7Q814VUP
Types de publication
Clinical Trial, Phase I
Clinical Trial, Phase II
Journal Article
Multicenter Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
258-267Références
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