Study to Evaluate Cinacalcet in Children With Chronic Kidney Disease

Chronic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01290029
• Other study ID #: 20090005
• Status: Completed
• Phase: Phase 1
• Start date: January 25, 2011
• Est. completion date: September 23, 2015

Study information

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

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: September 23, 2015
• Est. primary completion date: September 23, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 2190 Days

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Cinacalcet
Single, oral dose of 0.25 mg/kg cinacalcet

Locations

Country	Name	City	State
Germany	Research Site	Heidelberg
United Kingdom	Research Site	Bristol
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Leeds
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Nottingham
United States	Research Site	Kansas City	Missouri
United States	Research Site	Los Angeles	California
United States	Research Site	Louisville	Kentucky
United States	Research Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Germany,  United Kingdom, 

References & Publications (3)

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

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. Erratum in: Pediatr Nephrol. 2019 Apr;34(4):739-740. — 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	Number of Participants With Adverse Events	A serious adverse event is defined as an adverse event that meets at least 1 of the following serious criteria: • fatal • life threatening • requires in patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • congenital anomaly/birth defect • other medically important serious event. Treatment-related adverse events are those the investigator assessed as being possibly related to any study mandated activity (eg, administration of investigational product, protocol-required therapies, device(s) and/or procedure). Events of interest included acute pancreatitis, convulsions, drug related hepatic disorders, fractures, hypersensitivity, hypocalcemia, ischaemic heart disease, ventricular tachyarrhythmias, cardiac failure, and hypotension.	Day 1 to day 30
Secondary	Area Under the Plasma Concentration Time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) for Cinacalcet		Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
Secondary	Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUCinf) for Cinacalcet		Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
Secondary	Maximum Observed Plasma Concentration (Cmax) of Cinacalcet		Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
Secondary	Time to Reach Maximum Observed Plasma Concentration of Cinacalcet (Tmax)		Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
Secondary	Terminal Half-life of Cinacalcet	The terminal half-life (T1/2) of cinacalcet associated with the slope of the terminal phase.	Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose
Secondary	Percent Change From Baseline in Intact Parathyroid Hormone		Baseline (predose) and at 2, 8, 12 and 48 hours post-dose.
Secondary	Percent Change From Baseline in Total Calcium		Baseline (predose) and 2, 8, 12 and 48 hours post-dose.
Secondary	Percent Change From Baseline in Albumin Corrected Calcium		Baseline (predose) and 2, 8, 12 and 48 hours post-dose.
Secondary	Percent Change From Baseline in Ionized Calcium		Baseline (predose) and 2, 8, 12 and 48 hours post-dose.

External Links

•   AmgenTrials clinical trials website