Clinical trial NCT01290029: Study to Evaluate Cinacalcet in Children With Chronic Kidney Disease
Official title: An Open-label, Single-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cinacalcet HCl in Pediatric Subjects Aged 28 Days to Less Than 6 Years With Chronic Kidney Disease Receiving Dialysis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Kidney Disease
Hyperparathyroidism, Secondary
Secondary Hyperparathyroidism
Keywords: pediatric
CKD
dialysis
paediatric
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-02-04
Enrollment: 14
Sex: ALL
Minimum age (years): 28
Maximum age (years): 2190
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study was to evaluate the safety and tolerability of cinacalcet after a single oral dose in children aged 28 days to less than 6 years with chronic kidney disease receiving dialysis.


Eligibility criteria: Inclusion Criteria:

* Subject's parent, or legally acceptable guardian, must sign an Independent Ethics Committee (IEC) or Institutional Review Board (IRB) approved Informed Consent Form.
* Subjects 28 days to \< 6 years of age with chronic kidney disease (CKD) and secondary hyperparathyroidism (sHPT) as diagnosed by principal investigators, undergoing hemodialysis or peritoneal dialysis at the time of screening (subjects 6 months or older should have been receiving dialysis for ≥ 1 months) and who have not received any cinacalcet HCl therapy for at least 2 weeks prior to dosing on Day 1
* Free of any disease or condition (other than those diseases or conditions related to their renal disease that, in the opinion of the investigator, would impact the subject's safety or the integrity of the study data).
* Must weigh ≥ 6 kg at screening and at Day-1.
* Must be at least 30 weeks of gestational age.
* Physical examination must be acceptable to the investigator at screening and at Day -1.
* Hemoglobin ≥ 8 g/dL at screening and at Day -1.
* Serum calcium within age-appropriate normal ranges per the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) guidelines at screening and at Day -1
* Normal or clinically acceptable electrocardiogram (ECG) (12-lead reporting RR, PR, QRS, and QTc intervals) at screening and at Day -1.
* Clinical laboratory tests that are acceptable to the investigator at screening and at Day -1.

Exclusion Criteria

* Current or historic malignancy.
* Cardiac ventricular arrhythmias within 28 days prior to screening.
* A gastrointestinal disorder or surgery that could affect the absorption of drugs (eg, pyloric stenosis or any gut-shortening surgical procedure prior to screening).
* A new onset of seizure or worsening of a pre-existing seizure disorder within 2 months prior to IP administration.
* Major surgery (defined as any surgical procedure that involves general anesthesia or respiratory assistance) within 28 days prior to screening.
* Hepatic impairment indicated by elevated levels of hepatic transaminase or bilirubin (aspartate aminotransferase (AST) ≥ 1.5 x upper limit of normal (ULN) OR alanine aminotransferase (ALT) ≥ 1.5 x ULN OR total bilirubin ≥ 1 x ULN per institutional laboratory range) at screening or Day-1.
* History of prolongation of the QT interval (eg, congenital long QT interval, second or third degree heart block or other conditions which prolong the QT interval)
* Corrected QT Interval (QTc) \> 500 ms during screening, using Bazett's formula
* QTc ≥ 450 and ≤ 500 ms during screening, using Bazett's formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist
* Known hypersensitivity to cinacalcet HCl or any of the excipients in cinacalcet HCl.
* Use of grapefruit juice, herbal medications or potent CYP 3A4 inhibitors (eg, erythromycin, clarithromycin, ketokonazole, itraconazole) within the 14 days prior to enrollment and during the study.
* Concurrent or within 28 days prior to enrollment use of medications that are predominantly metabolized by the enzyme CYP2D6 and have a narrow therapeutic index (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants such as desipramine and imipramine, and beta-blockers such as metoprolol or carvedilol).
* Concurrent or within 28 days prior to enrollment use of medications that prolong QT interval (eg, sotalol, amiodarone, erythromycin, or clarithromycin).
* Currently receiving treatment in another investigational device or drug study, or less than 90 days since ending treatment on another investigational device or drug study(s).
* Other investigational procedures while participating in this study are excluded.

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Day 1 to day 30
Secondary outcomes:
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) for Cinacalcet
timeFrame: Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
measure: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf) for Cinacalcet
timeFrame: Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
measure: Maximum Observed Plasma Concentration (Cmax) of Cinacalcet
timeFrame: Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration of Cinacalcet (Tmax)
timeFrame: Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
measure: Terminal Half-life of Cinacalcet
timeFrame: Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
measure: Percent Change From Baseline in Intact Parathyroid Hormone
timeFrame: Baseline (predose) and at 2, 8, 12 and 48 hours post-dose.
measure: Percent Change From Baseline in Total Calcium
timeFrame: Baseline (predose) and 2, 8, 12 and 48 hours post-dose.
measure: Percent Change From Baseline in Albumin Corrected Calcium
timeFrame: Baseline (predose) and 2, 8, 12 and 48 hours post-dose.
measure: Percent Change From Baseline in Ionized Calcium
timeFrame: Baseline (predose) and 2, 8, 12 and 48 hours post-dose.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Heidelberg
country: Germany
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Chen P, Sohn W, Narayanan A, Gisleskog PO, Melhem M. Bridging adults and paediatrics with secondary hyperparathyroidism receiving haemodialysis: a pharmacokinetic-pharmacodynamic analysis of cinacalcet. Br J Clin Pharmacol. 2019 Jun;85(6):1312-1325. doi: 10.1111/bcp.13900. Epub 2019 Apr 25.
citation: Sohn WY, Portale AA, Salusky IB, Zhang H, Yan LL, Ertik B, Shahinfar S, Lee E, Dehmel B, Warady BA. 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. Pediatr Nephrol. 2019 Jan;34(1):145-154. doi: 10.1007/s00467-018-4054-8. Epub 2018 Aug 23.
citation: Warady BA, Ng E, Bloss L, Mo M, Schaefer F, Bacchetta J. Cinacalcet studies in pediatric subjects with secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. 2020 Sep;35(9):1679-1697. doi: 10.1007/s00467-020-04516-4. Epub 2020 May 4.