Clinical trial NCT01439867: Safety & Tolerability of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism
Official title: An Open-label, Single-arm Study to Assess the Safety & Tolerability of Cinacalcet in Addition to Standard of Care in Pediatric Subjects Age 28 Days to < 6 Yrs With Chronic Kidney Disease & Secondary Hyperparathyroidism Receiving Dialysis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Hyperparathyroidism, Secondary
Keywords: Dialysis
Sensipar
Mimpara
Hemodialysis
Peritoneal Dialysis
Renal
Parathyroid hormone
Pediatric
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-09-23
Enrollment: 18
Sex: ALL
Minimum age (years): 28
Maximum age (years): 2189
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective was to characterize corrected serum calcium levels on treatment with cinacalcet in pediatric patients with secondary hyperparathyroidism (HPT).

Detailed description: This is a multicenter, 26-week, single-arm, open-label, safety study. Participants were to remain on study for 26 weeks or until time of kidney transplantation, whichever came first.

The study and enrollment was placed on partial clinical hold in February 2013 which resulted in changes to the protocol. The study was restarted in April 2014 following these changes.

Participants who completed the 26-week study or were on study when the study was closed in June 2016 were eligible to participate in an open-label extension study (Study 20140159; NCT02341417).

Eligibility criteria: Inclusion criteria:

* Subjects between the ages of 28 days to \< 6 years of age at enrollment (Czech Republic minimum age is ≥ 2 years of age at enrollment)
* Screening plasma iPTH level \> 300 pg/mL (31.8 pmol/L) from the central laboratory, and not have received any cinacalcet therapy for at least 30 days prior to start of dosing
* Screening corrected calcium from the central laboratory:
* ≥ 9.4 mg/dL (2.35 mmol/L) if age 28 days to \< 2 years
* ≥ 8.8 (2.2 mmol/L) if age ≥ 2 to \< 6 years
* Serum phosphorus from the central laboratory:
* ≥ 5.0 mg/dL (1.25 mmol/L) if age 28 days to \< 1 year
* ≥ 4.5 mg/dL (1.13 mmol/L) if age ≥ 1 to \< 6 years
* SHPT not due to vitamin D deficiency, per investigator assessment
* Dry weight ≥ 7 kg at the time of screening

Exclusion criterion:

* History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrhythmias or other conditions associated with prolonged QT interval
* Corrected QT interval (QTc) \> 500 ms, using Bazett's formula
* QTc ≥ 450 to ≤ 500 ms, using Bazett's formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist
* Use of grapefruit juice, herbal medications, or potent CYP 3A4 inhibitors (e.g., erythromycin, clarithromycin, ketoconazole, itraconazole)
* Use of concomitant medications that may prolong the QTc interval (e.g., ondansetron, albuterol)

Primary outcomes:
measure: Percentage of Participants With Hypocalcemia
timeFrame: 26 weeks
Secondary outcomes:
measure: Percentage of Participants With Corrected Serum Calcium Levels < 8.8 mg/dL (2.2 mmol/L) During the Study
timeFrame: 26 weeks
measure: Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)
timeFrame: Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
measure: Percent Change From Baseline in Corrected Serum Calcium
timeFrame: Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
measure: Percent Change From Baseline in Serum Phosphorous
timeFrame: Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
measure: Percent Change From Baseline in Calcium Phosphorus Product (Ca x P)
timeFrame: Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
measure: Percentage of Participants Who Achieved > 30% Reduction in iPTH From Baseline at Any Two Consecutive Measurements
timeFrame: 26 weeks
measure: Percentage of Participants Who Achieved ≥ 30% Reduction in iPTH From Baseline During the Study
timeFrame: 26 weeks
measure: Percentage of Participants Who Achieved iPTH Values Between 200 and 300 pg/mL at Any Two Consecutive Measurements
timeFrame: 26 weeks
measure: Percentage of Participants Who Achieved iPTH Values < 300 pg/mL During the Study
timeFrame: 26 weeks
measure: Dose- and Weight-Normalized Maximum Plasma Concentration (Cmax) of Cinacalcet
timeFrame: Week 12
measure: Dose- and Weight-Normalized Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet
timeFrame: Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Kansas City
country: United States
facility: Research Site
state: Missouri
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Bronx
country: United States
facility: Research Site
state: New York
city: Greenville
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Oklahoma City
country: United States
facility: Research Site
state: Oklahoma
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Bruxelles
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Leuven
country: Belgium
facility: Research Site
city: Praha 5
country: Czechia
facility: Research Site
city: Bron cedex
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Szeged
country: Hungary
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Torino
country: Italy
facility: Research Site
city: Chihuahua
country: Mexico
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Grafton, Auckland
country: New Zealand
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Kosice
country: Slovakia
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: 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.