An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis.
PMCID: PMC6244811 DOI: 10.1007/s00467-018-4054-8
BACKGROUND: Calcimimetics, shown to control biochemical parameters of secondary hyperparathyroidism (SHPT), have well-established safety and pharmacokinetic profiles in adult end-stage renal disease subjects treated with dialysis; however, such studies are limited in pediatric subjects.
METHODS: In this study, the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of cinacalcet were evaluated in children with chronic kidney disease (CKD) and SHPT receiving dialysis. Twelve subjects received a single dose of cinacalcet (0.25 mg/kg) orally or by nasogastric or gastric tube. Subjects were randomized to one of two parathyroid hormone (PTH) and serum calcium sampling sequences: [(1) 2, 8, 48 h; or (2) 2, 12, 48 h] and assessed for 72 h after dosing.
RESULTS: Median plasma cinacalcet tmax was 1 h (range 0.5-4.0 h); mean (SD) Cmax and AUClast were 2.83 (1.98) ng/mL and 11.8 (8.74) h*ng/mL, respectively; mean (SD) half-life (t1/2) was 3.70 (2.57) h. Dose adjustments, based upon body weight (mg/kg), minimized the effects of age, body weight, body surface area, and body mass index on cinacalcet PK. Reductions in serum PTH levels from baseline were observed at 2 to 8 h post-dose (median 10.8 and 29.6%, respectively), returned towards baseline by 12-72 h and were inversely related to changes in the plasma cinacalcet PK profile. Single-dose cinacalcet was well-tolerated with no unexpected safety findings and a PK/PD, safety profile similar to adults.
CONCLUSIONS: In conclusion, a single 0.25 mg/kg dose of cinacalcet was evaluated to be a safe starting dose in these children aged < 6 years.
Pediatric nephrology (Berlin, Germany)
Renal Insufficiency, Chronic; Cinacalcet; Parathyroid Hormone; Renal Dialysis; Hyperparathyroidism, Secondary; Child; Adolescent
Calcimimetics; Chronic kidney disease; Cinacalcet; Parathyroid hormone; Pediatric dialysis patients; Secondary hyperparathyroidism
Sohn, Winnie Y.; Portale, Anthony A.; Salusky, Isidro B.; Zhang, Hao; Yan, Lucy L.; Ertik, Bella; Shahinfar, Shahnaz; Lee, Edward; Dehmel, Bastian; and Warady, Bradley A., "An open-label, single-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cinacalcet in pediatric subjects aged 28 days to < 6 years with chronic kidney disease receiving dialysis." (2019). Manuscripts, Articles, Book Chapters and Other Papers. 1328.