Study to Evaluate Cinacalcet in Children With Chronic Kidney Disease

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Kidney Disease, Hyperparathyroidism, Secondary, Secondary Hyperparathyroidism

Intervention / Treatment
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* Drug: Cinacalcet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 28 Days
Maximum Age: 2190 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cinacalcet<br>Participants received a single, oral dose of 0.25 mg/kg cinacalcet. | Drug: Cinacalcet<br>* Single, oral dose of 0.25 mg/kg cinacalcet<br>* Other names: Mimpara®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 Total Calcium |  | Baseline (predose) and 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. | 
| Percent Change From Baseline in Ionized Calcium |  | Baseline (predose) and 2, 8, 12 and 48 hours post-dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pediatric, CKD, dialysis, paediatric