Safety & Tolerability of Cinacalcet in Pediatric Patients With Chronic Kidney Disease and Secondary Hyperparathyroidism

Chronic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01439867
• Other study ID #: 20110100
• Secondary ID: 2011-004618-40
• Status: Terminated
• Phase: Phase 2
• Start date: June 22, 2012
• Est. completion date: June 3, 2016

Study information

• Verified date: June 2020
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 18
• Est. completion date: June 3, 2016
• Est. primary completion date: June 3, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2189 Days

Eligibility

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)

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Hyperparathyroidism
• Hyperparathyroidism, Secondary
• Kidney Diseases
• Neoplasm Metastasis
• Renal Insufficiency, Chronic

Intervention

Drug:
• Cinacalcet hydrochloride
Cinacalcet was provided as 5 mg capsules that were opened, and the contents were either sprinkled on soft food or suspended into a sucrose syrup to create a liquid suspension for administration. All doses were administered with food or shortly after a meal at the same time daily.
• Standard of Care
Standard of care may have included vitamin D sterols (25 OH vitamin D and/or 1-25 OH vitamin D and its analogs) at the discretion of the investigator.

Locations

Country	Name	City	State
Belgium	Research Site	Bruxelles
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Czechia	Research Site	Praha 5
France	Research Site	Bron cedex
France	Research Site	Lille
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Paris
Germany	Research Site	Heidelberg
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Szeged
Italy	Research Site	Genova
Italy	Research Site	Roma
Italy	Research Site	Torino
Mexico	Research Site	Chihuahua
Netherlands	Research Site	Amsterdam
New Zealand	Research Site	Grafton, Auckland
Poland	Research Site	Gdansk
Poland	Research Site	Krakow
Poland	Research Site	Warszawa
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Saint Petersburg
Slovakia	Research Site	Kosice
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Baltimore	Maryland
United States	Research Site	Birmingham	Alabama
United States	Research Site	Bronx	New York
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Dallas	Texas
United States	Research Site	Greenville	North Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Iowa City	Iowa
United States	Research Site	Kansas City	Missouri
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Saint Louis	Missouri
United States	Research Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  France,  Germany,  Hungary,  Italy,  Mexico,  Netherlands,  New Zealand,  Poland,  Russian Federation,  Slovakia, 

References & Publications (2)

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. — View 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 May 4. doi: 10.1007/s00467-020-04516-4. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Hypocalcemia	Hypocalcemia was defined as corrected serum calcium levels < 9.0 mg/dL (2.25 mmol/L) for participants aged 28 days to < 2 years, and < 8.4 mg/dL (2.1 mmol/L) for participants aged = 2 years to < 6 years at any time during the study.	26 weeks
Secondary	Percentage of Participants With Corrected Serum Calcium Levels < 8.8 mg/dL (2.2 mmol/L) During the Study		26 weeks
Secondary	Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)		Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
Secondary	Percent Change From Baseline in Corrected Serum Calcium		Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
Secondary	Percent Change From Baseline in Serum Phosphorous		Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
Secondary	Percent Change From Baseline in Calcium Phosphorus Product (Ca x P)		Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
Secondary	Percentage of Participants Who Achieved > 30% Reduction in iPTH From Baseline at Any Two Consecutive Measurements	A participant was considered to have achieved > 30% reduction in iPTH from baseline at any 2 consecutive measurements if percent change of any two consecutive post-baseline iPTH values were < -30% regardless if there was a missing value in between.	26 weeks
Secondary	Percentage of Participants Who Achieved = 30% Reduction in iPTH From Baseline During the Study	A participant was considered to have achieved = 30% reduction in iPTH if the percent change of any post-baseline iPTH value was = -30% from baseline.	26 weeks
Secondary	Percentage of Participants Who Achieved iPTH Values Between 200 and 300 pg/mL at Any Two Consecutive Measurements	A participant was considered to have achieved iPTH between 200 and 300 pg/mL (21.2 and 31.8 pmol/L) at any 2 consecutive measurements if any two consecutive post-baseline iPTH values were within the range regardless if there was a missing value in between. The analysis included all enrolled subjects with at least 1 post-baseline assessment.	26 weeks
Secondary	Percentage of Participants Who Achieved iPTH Values < 300 pg/mL During the Study	A participant was considered to have achieved iPTH < 300 pg/mL (31.8 pmol/L) during the study if any post-baseline iPTH value was < 300 pg/mL.	26 weeks
Secondary	Dose- and Weight-Normalized Maximum Plasma Concentration (Cmax) of Cinacalcet		Week 12
Secondary	Dose- and Weight-Normalized Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet		Week 12

External Links

•   AmgenTrials clinical trials website