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

• ClinicalTrials.gov Identifier: NCT01439867
• Recruitment Status: Terminated
• First Posted: September 23, 2011
• Results First Posted: August 11, 2017
• Last Update Posted: June 17, 2020
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease; Hyperparathyroidism, Secondary	Drug: Cinacalcet hydrochloride; Drug: Standard of Care	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: June 22, 2012
• Actual Primary Completion Date: June 3, 2016
• Actual Study Completion Date: June 3, 2016

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Hypocalcemia [ Time Frame: 26 weeks ]
   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.

Secondary Outcome Measures :

1. Percentage of Participants With Corrected Serum Calcium Levels < 8.8 mg/dL (2.2 mmol/L) During the Study [ Time Frame: 26 weeks ]
2. Percent Change From Baseline in Intact Parathyroid Hormone (iPTH) [ Time Frame: Baseline and weeks 3, 7, 11, 15, 19, 22, and 24 ]
3. Percent Change From Baseline in Corrected Serum Calcium [ Time Frame: Baseline and weeks 3, 7, 11, 15, 19, 22, and 24 ]
4. Percent Change From Baseline in Serum Phosphorous [ Time Frame: Baseline and weeks 3, 7, 11, 15, 19, 22, and 24 ]
5. Percent Change From Baseline in Calcium Phosphorus Product (Ca x P) [ Time Frame: Baseline and weeks 3, 7, 11, 15, 19, 22, and 24 ]
6. Percentage of Participants Who Achieved > 30% Reduction in iPTH From Baseline at Any Two Consecutive Measurements [ Time Frame: 26 weeks ]
   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.
7. Percentage of Participants Who Achieved ≥ 30% Reduction in iPTH From Baseline During the Study [ Time Frame: 26 weeks ]
   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.
8. Percentage of Participants Who Achieved iPTH Values Between 200 and 300 pg/mL at Any Two Consecutive Measurements [ Time Frame: 26 weeks ]
   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.
9. Percentage of Participants Who Achieved iPTH Values < 300 pg/mL During the Study [ Time Frame: 26 weeks ]
   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.
10. Dose- and Weight-Normalized Maximum Plasma Concentration (Cmax) of Cinacalcet [ Time Frame: Week 12 ]
11. Dose- and Weight-Normalized Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Cinacalcet [ Time Frame: Week 12 ]

Eligibility Criteria

• Ages Eligible for Study: 28 Days to 2189 Days (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, Alabama

Research Site

Birmingham, Alabama, United States, 35233

United States, Arkansas

Research Site

Little Rock, Arkansas, United States, 72202

United States, California

Research Site

Los Angeles, California, United States, 90095

United States, Iowa

Research Site

Iowa City, Iowa, United States, 52242

United States, Kentucky

Research Site

Louisville, Kentucky, United States, 40202

United States, Maryland

Research Site

Baltimore, Maryland, United States, 21287

United States, Michigan

Research Site

Ann Arbor, Michigan, United States, 48109

United States, Missouri

Research Site

Kansas City, Missouri, United States, 64108

Research Site

Saint Louis, Missouri, United States, 63110

United States, New York

Research Site

Bronx, New York, United States, 10467

United States, North Carolina

Research Site

Greenville, North Carolina, United States, 27834

United States, Ohio

Research Site

Cincinnati, Ohio, United States, 45229

United States, Oklahoma

Research Site

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Research Site

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

Research Site

Dallas, Texas, United States, 75390

Research Site

Houston, Texas, United States, 77030

Research Site

San Antonio, Texas, United States, 78229

Belgium

Research Site

Bruxelles, Belgium, 1020

Research Site

Gent, Belgium, 9000

Research Site

Leuven, Belgium, 3000

Czechia

Research Site

Praha 5, Czechia, 150 06

France

Research Site

Bron cedex, France, 69677

Research Site

Lille, France, 59800

Research Site

Paris, France, 75012

Research Site

Paris, France, 75015

Research Site

Paris, France, 75019

Germany

Research Site

Heidelberg, Germany, 69120

Hungary

Research Site

Budapest, Hungary, 1083

Research Site

Debrecen, Hungary, 4032

Research Site

Szeged, Hungary, 6720

Italy

Research Site

Genova, Italy, 16147

Research Site

Roma, Italy, 00165

Research Site

Torino, Italy, 10126

Mexico

Research Site

Chihuahua, Mexico, 31000

Netherlands

Research Site

Amsterdam, Netherlands, 1105 AZ

New Zealand

Research Site

Grafton, Auckland, New Zealand, 1023

Poland

Research Site

Gdansk, Poland, 80-952

Research Site

Krakow, Poland, 30-663

Research Site

Warszawa, Poland, 00-576

Russian Federation

Research Site

Moscow, Russian Federation, 107014

Research Site

Saint Petersburg, Russian Federation, 198205

Slovakia

Research Site

Kosice, Slovakia, 040 11

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

Publications:

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.

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.

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT01439867
• Other Study ID Numbers: 20110100; 2011-004618-40 ( EudraCT Number )
• First Posted: September 23, 2011
• Results First Posted: August 11, 2017
• Last Update Posted: June 17, 2020
• Last Verified: June 2020

Keywords provided by Amgen:

Dialysis; Sensipar; Mimpara; Hemodialysis; Peritoneal Dialysis; Renal; Parathyroid hormone; Pediatric

Additional relevant MeSH terms:

Neoplasm Metastasis; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Hyperparathyroidism, Secondary; Urologic Diseases; Neoplastic Processes; Neoplasms; Pathologic Processes; Renal Insufficiency; Parathyroid Diseases; Endocrine System Diseases; Cinacalcet; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Calcimimetic Agents; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists