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

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

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

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Disease; Hyperparathyroidism, Secondary
• Intervention / Treatment: Drug: Cinacalcet hydrochloride; Drug: Standard of Care

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).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1020
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
• Czechia
  • Praha 5, Czechia, 150 06
    • Research Site
• France
  • Bron cedex, France, 69677
    • Research Site
  • Lille, France, 59800
    • Research Site
  • Paris, France, 75012
    • Research Site
  • Paris, France, 75015
    • Research Site
  • Paris, France, 75019
    • Research Site
• Germany
  • Heidelberg, Germany, 69120
    • Research Site
• Hungary
  • Budapest, Hungary, 1083
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Szeged, Hungary, 6720
    • Research Site
• Italy
  • Genova, Italy, 16147
    • Research Site
  • Roma, Italy, 00165
    • Research Site
  • Torino, Italy, 10126
    • Research Site
• Mexico
  • Chihuahua, Mexico, 31000
    • Research Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Research Site
• New Zealand
  • Grafton, Auckland, New Zealand, 1023
    • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Krakow, Poland, 30-663
    • Research Site
  • Warszawa, Poland, 00-576
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 107014
    • Research Site
  • Saint Petersburg, Russian Federation, 198205
    • Research Site
• Slovakia
  • Kosice, Slovakia, 040 11
    • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Research Site
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Research Site
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Research Site
    • Saint Louis, Missouri, United States, 63110
      • Research Site
  • New York
    • Bronx, New York, United States, 10467
      • Research Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75390
      • Research Site
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 5 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cinacalcet; Prior to the partial clinical hold, the starting dose was 0.25 mg/kg (based on dry weight) and was titrated upwards (maximum allowed daily dose of 4.2 mg/kg) based on plasma intact parathyroid hormone (iPTH), corrected serum calcium levels obtained monthly, and adverse signs and symptoms. After the partial clinical hold the starting dose was 0.20 mg/kg (based on dry weight) and was titrated upwards (maximum allowed daily dose of 2.5 or 60 mg, whichever was lower) based on plasma iPTH, corrected serum calcium levels obtained monthly, weekly monitoring of ionized calcium levels, and adverse signs and symptoms. All participants also received standard of care, which may have included vitamin D sterols.

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.; Other Names: Sensipar®; Mimpara®; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Corrected Serum Calcium Levels < 8.8 mg/dL (2.2 mmol/L) During the Study		26 weeks
Percent Change From Baseline in Intact Parathyroid Hormone (iPTH)		Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
Percent Change From Baseline in Corrected Serum Calcium		Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
Percent Change From Baseline in Serum Phosphorous		Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
Percent Change From Baseline in Calcium Phosphorus Product (Ca x P)		Baseline and weeks 3, 7, 11, 15, 19, 22, and 24
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
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
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
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
Dose- and Weight-Normalized Maximum Plasma Concentration (Cmax) of Cinacalcet		Week 12
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

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2012
• Primary Completion (Actual): June 3, 2016
• Study Completion (Actual): June 3, 2016

Study Registration Dates

• First Submitted: September 22, 2011
• First Submitted That Met QC Criteria: September 22, 2011
• First Posted (Estimate): September 23, 2011

Study Record Updates

• Last Update Posted (Actual): June 17, 2020
• Last Update Submitted That Met QC Criteria: June 12, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Pediatric; Dialysis; Hemodialysis; Sensipar; Mimpara; Peritoneal Dialysis; Renal; Parathyroid hormone
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Cinacalcet
• Other Study ID Numbers: 20110100; 2011-004618-40 (EudraCT Number)