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A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis.
Pediatr Nephrol. 2019 03; 34(3):475-486.PN

Abstract

BACKGROUND

This randomized phase 3 study evaluated the efficacy and safety of cinacalcet in children with secondary hyperparathyroidism (SHPT) receiving dialysis.

METHODS

This study had double-blind and open-label phases. Eligible patients aged 6-< 18 years were randomized to cinacalcet (starting dose ≤ 0.20 mg/kg) or placebo. The primary endpoint was ≥ 30% reduction from baseline in mean intact parathyroid hormone (iPTH). Secondary endpoints included mean iPTH ≤ 300 pg/mL; percentage change from baseline in corrected total serum calcium, phosphorus, and calcium phosphorus product (Ca × P); and safety.

RESULTS

The double-blind phase comprised 43 patients (cinacalcet, n = 22; placebo, n = 21). Nineteen months into the study, regulatory authorities were notified of a fatality; the study was subsequently terminated after a 14-month clinical hold. Before the hold, 12 patients (55%) on cinacalcet and four (19%) on placebo achieved the primary endpoint (p = 0.017), and 27% and 24%, respectively, achieved iPTH ≤ 300 pg/mL. The between-group differences (95% CI) in percentage changes for total serum calcium, phosphorus, and Ca × P were - 4% (- 9 to 1%), - 6% (- 21 to 8%), and - 10% (- 23 to 3%). The mean maximum actual weight-adjusted daily cinacalcet dosage administered was 0.99 mg/kg/day. Overall, 82% of patients on cinacalcet and 86% on placebo had ≥ 1 treatment-emergent adverse event; the most common were vomiting (32%, 24%, respectively), hypocalcemia (23%, 19%), nausea (18%, 14%), and hypertension (14%, 24%).

CONCLUSIONS

Despite early termination, efficacy and safety outcomes observed with cinacalcet in children with SHPT on dialysis were consistent with adult observations, suggesting cinacalcet may meet an unmet medical need for this population.

Authors+Show Affiliations

Division of Pediatric Nephrology, Children's Mercy Kansas City, 2401 Gillham Road, 2MOB.17, Kansas City, MO, 64108, USA. bwarady@cmh.edu.Amgen Inc., Thousand Oaks, CA, USA.University Hospital Vall d' Hebron, Barcelona, Spain.Amgen Europe GmbH, Zug, Switzerland.Brody School of Medicine, East Carolina University, Greenville, NC, USA.Amgen Inc., Thousand Oaks, CA, USA.Children's Hospital of Philadelphia, Philadelphia, PA, USA.Children's Hospital of Philadelphia, Philadelphia, PA, USA. S. Shahinfar Consulting Inc., Newtown Square, PA, USA.Ghent University, Safedpedrug, Ghent, Belgium.Heidelberg University Hospital, Heidelberg, Germany.

Pub Type(s)

Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30506144

Citation

Warady, Bradley A., et al. "A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis." Pediatric Nephrology (Berlin, Germany), vol. 34, no. 3, 2019, pp. 475-486.
Warady BA, Iles JN, Ariceta G, et al. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. 2019;34(3):475-486.
Warady, B. A., Iles, J. N., Ariceta, G., Dehmel, B., Hidalgo, G., Jiang, X., Laskin, B., Shahinfar, S., Vande Walle, J., & Schaefer, F. (2019). A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis. Pediatric Nephrology (Berlin, Germany), 34(3), 475-486. https://doi.org/10.1007/s00467-018-4116-y
Warady BA, et al. A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis. Pediatr Nephrol. 2019;34(3):475-486. PubMed PMID: 30506144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis. AU - Warady,Bradley A, AU - Iles,Janet N, AU - Ariceta,Gema, AU - Dehmel,Bastian, AU - Hidalgo,Guillermo, AU - Jiang,Xun, AU - Laskin,Benjamin, AU - Shahinfar,Shahnaz, AU - Vande Walle,Johan, AU - Schaefer,Franz, Y1 - 2018/11/30/ PY - 2018/05/15/received PY - 2018/10/10/accepted PY - 2018/10/05/revised PY - 2018/12/7/pubmed PY - 2020/5/6/medline PY - 2018/12/4/entrez KW - Calcimimetics KW - Chronic kidney disease KW - Cinacalcet KW - Parathyroid hormone KW - Pediatric patients KW - Secondary hyperparathyroidism SP - 475 EP - 486 JF - Pediatric nephrology (Berlin, Germany) JO - Pediatr Nephrol VL - 34 IS - 3 N2 - BACKGROUND: This randomized phase 3 study evaluated the efficacy and safety of cinacalcet in children with secondary hyperparathyroidism (SHPT) receiving dialysis. METHODS: This study had double-blind and open-label phases. Eligible patients aged 6-< 18 years were randomized to cinacalcet (starting dose ≤ 0.20 mg/kg) or placebo. The primary endpoint was ≥ 30% reduction from baseline in mean intact parathyroid hormone (iPTH). Secondary endpoints included mean iPTH ≤ 300 pg/mL; percentage change from baseline in corrected total serum calcium, phosphorus, and calcium phosphorus product (Ca × P); and safety. RESULTS: The double-blind phase comprised 43 patients (cinacalcet, n = 22; placebo, n = 21). Nineteen months into the study, regulatory authorities were notified of a fatality; the study was subsequently terminated after a 14-month clinical hold. Before the hold, 12 patients (55%) on cinacalcet and four (19%) on placebo achieved the primary endpoint (p = 0.017), and 27% and 24%, respectively, achieved iPTH ≤ 300 pg/mL. The between-group differences (95% CI) in percentage changes for total serum calcium, phosphorus, and Ca × P were - 4% (- 9 to 1%), - 6% (- 21 to 8%), and - 10% (- 23 to 3%). The mean maximum actual weight-adjusted daily cinacalcet dosage administered was 0.99 mg/kg/day. Overall, 82% of patients on cinacalcet and 86% on placebo had ≥ 1 treatment-emergent adverse event; the most common were vomiting (32%, 24%, respectively), hypocalcemia (23%, 19%), nausea (18%, 14%), and hypertension (14%, 24%). CONCLUSIONS: Despite early termination, efficacy and safety outcomes observed with cinacalcet in children with SHPT on dialysis were consistent with adult observations, suggesting cinacalcet may meet an unmet medical need for this population. SN - 1432-198X UR - https://wwww.unboundmedicine.com/medline/citation/30506144/A_randomized_double_blind_placebo_controlled_study_to_assess_the_efficacy_and_safety_of_cinacalcet_in_pediatric_patients_with_chronic_kidney_disease_and_secondary_hyperparathyroidism_receiving_dialysis_ L2 - https://dx.doi.org/10.1007/s00467-018-4116-y DB - PRIME DP - Unbound Medicine ER -