Study to Evaluate Cinacalcet in Children With Chronic Kidney Disease

Phase 1

Completed

Conditions: Chronic Kidney Disease
Hyperparathyroidism, Secondary
Secondary Hyperparathyroidism

Interventions: Drug: Cinacalcet

Registration Number: NCT01290029

Lead Sponsor: Amgen

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 14

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.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cinacalcet	Cinacalcet	Participants received a single, oral dose of 0.25 mg/kg cinacalcet.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	Day 1 to day 30	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.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline in Total Calcium	Baseline (predose) and 2, 8, 12 and 48 hours post-dose.
Percent Change From Baseline in Ionized Calcium	Baseline (predose) and 2, 8, 12 and 48 hours post-dose.
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
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
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
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
Terminal Half-life of Cinacalcet	Baseline (predose) and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours post-dose	The terminal half-life (T1/2) of cinacalcet associated with the slope of the terminal phase.
Percent Change From Baseline in Intact Parathyroid Hormone	Baseline (predose) and at 2, 8, 12 and 48 hours post-dose.
Percent Change From Baseline in Albumin Corrected Calcium	Baseline (predose) and 2, 8, 12 and 48 hours post-dose.