Clinical drug investigation · 2018
Pharmacokinetics, Pharmacodynamics, and Safety of the Novel Calcimimetic Agent Evocalcet in Healthy Japanese Subjects: First-in-Human Phase I Study.
Клиническое исследование I фазыКонтролируемое клиническое исследованиеСтатьяНазвание и аннотация: Перевод в очереди
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Akizawa Tadao, Shimazaki Ryutaro, Shiramoto Masanari, Fukagawa Masafumi, Evocalcet Study Group
Аннотация
BACKGROUND AND OBJECTIVES: Evocalcet is a novel calcimimetic agent with potential to improve the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. This study aimed to determine the pharmacokinetics, pharmacodynamics, and safety of evocalcet in healthy Japanese subjects.
METHODS: This was a single-blind, placebo-controlled, single-dose study and an 8-day multiple-dose study of evocalcet (MT-4580/KHK7580) in 66 healthy Japanese subjects.
RESULTS: After a single dose of evocalcet 1-20 mg, the time to maximum plasma concentration was attained in 1.5-2 h (median), and the elimination half-life was 12.98-19.77 h (mean). Within this dose range, the maximum plasma concentration and area under plasma concentration-time curve increased dose proportionally, confirming linearity. The trough plasma concentrations were relatively unchanged after multiple administration of evocalcet 6 and 12 mg. Evocalcet decreased intact parathyroid hormone and corrected calcium and phosphorus levels in a dose-proportional manner. Regarding its safety, no upper gastrointestinal adverse event occurred after the single and multiple administration of evocalcet at doses up to 12 mg. Tetany was detected in 1 subject (17%) after multiple administration of evocalcet 12 mg. In healthy subjects, the tolerability and safety of evocalcet were observed for a single dose of evocalcet at doses up to 20 mg, and for multiple doses up to 12 mg.
CONCLUSIONS: These results suggest that evocalcet may have a comparable efficacy and better safety profile than that of cinacalcet, one of the current treatments for secondary hyperparathyroidism in patients with chronic kidney disease.
METHODS: This was a single-blind, placebo-controlled, single-dose study and an 8-day multiple-dose study of evocalcet (MT-4580/KHK7580) in 66 healthy Japanese subjects.
RESULTS: After a single dose of evocalcet 1-20 mg, the time to maximum plasma concentration was attained in 1.5-2 h (median), and the elimination half-life was 12.98-19.77 h (mean). Within this dose range, the maximum plasma concentration and area under plasma concentration-time curve increased dose proportionally, confirming linearity. The trough plasma concentrations were relatively unchanged after multiple administration of evocalcet 6 and 12 mg. Evocalcet decreased intact parathyroid hormone and corrected calcium and phosphorus levels in a dose-proportional manner. Regarding its safety, no upper gastrointestinal adverse event occurred after the single and multiple administration of evocalcet at doses up to 12 mg. Tetany was detected in 1 subject (17%) after multiple administration of evocalcet 12 mg. In healthy subjects, the tolerability and safety of evocalcet were observed for a single dose of evocalcet at doses up to 20 mg, and for multiple doses up to 12 mg.
CONCLUSIONS: These results suggest that evocalcet may have a comparable efficacy and better safety profile than that of cinacalcet, one of the current treatments for secondary hyperparathyroidism in patients with chronic kidney disease.