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
This randomized phase 3 study evaluated the efficacy and safety of cinacalcet in children with secondary hyperparathyroidism (SHPT) receiving dialysis.
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.
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%).
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.
KeywordsCalcimimetics Chronic kidney disease Cinacalcet Parathyroid hormone Pediatric patients Secondary hyperparathyroidism
The authors acknowledge Meghan Johnson, PhD, and James Balwit, MS, CMPP (Complete Healthcare Communications, LLC, a CHC Group company, North Wales, PA), whose work was funded by Amgen Inc., as well as Holly Tomlin, MPH, CMPP (Amgen Inc. at time of writing, currently Tomlin Health Sciences Communications), and William W. Stark, Jr., PhD (Amgen employee and stockholder), for the assistance in writing this manuscript.
This study was funded by Amgen Inc.
Compliance with ethical standards
Conflicts of interest
BAW and SS have served as consultants for Amgen Inc. JNI was an employee and stockholder of Amgen Inc. at the time the work was done. BD was an employee of Amgen Europe GmbH at the time the work was done. GH has received grant funding from Amgen Inc. XJ is an employee and stockholder of Amgen Inc. BL was the principal investigator for a clinical study site for the study described in this manuscript. JVW is a member of the Ferring Safety Board, Astellas Safety and Investigator Board for Solifenacin, Mitsubishi Safety Board, and Alexion Registry Review Board and receives research funding and is on the speakers bureau for Alexion Pharmaceuticals, Inc. FS has received personal fees from Amgen Inc. GA declares no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
The study protocol was approved by the institutional review board or independent ethics committee of each study center.
Informed consent or assent, when applicable, because the youngest participants cannot consent, was obtained from all individual participants included in the study and/or their parent or legally acceptable representative.
There is a plan to share data. This may include de-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request, also related data dictionaries, study protocol, statistical analysis plan, informed consent form, and/or clinical study report. Data sharing requests relating to data in this manuscript will be considered after the publication date and (1) this product and indication (or other new use) have been granted marketing authorization in both the USA and Europe, or (2) clinical development discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for these data. Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labeling. A committee of internal advisors reviews requests. If not approved, requests may be further arbitrated by a Data Sharing Independent Review Panel. Requests that pose a potential conflict of interest or an actual or potential competitive risk may be declined at Amgen’s sole discretion and without further arbitration. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the following: http://www.amgen.com/datasharing.
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