Efficacy and Safety of Cinacalcet in Pediatric Patients With Secondary Hyperparathyroidism (SHPT) and Chronic Kidney Disease (CKD) on Dialysis

Study Overview
=================
Brief Summary
-----------------
The primary objective was to evaluate the efficacy of cinacalcet for reducing the plasma intact parathyroid hormone (iPTH) level by ≥ 30%.

Detailed Description
-----------------
This was a 24-week, randomized, multicenter, open-label, controlled study. Participants were randomized into one of two treatment arms; oral administration of cinacalcet daily in addition to standard of care treatment, or standard of care alone. Randomization was stratified by age group (6 to < 12 and 12 to < 18 years of age). All participants received standard of care which could include therapy with Vitamin D sterols, calcium supplementation, and phosphate binders. Participants in both treatment groups who completed the 20-week treatment period and those who ended the study due to study closure were eligible to enroll in an open-label extension study (20140159; NCT02341417) for further safety follow-up.

Official Title
-----------------
A Randomized, Open-label, Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Pediatric Subjects With Secondary Hyperparathyroidism and Chronic Kidney Disease Receiving Dialysis

Conditions
-----------------
Chronic Kidney Disease, Secondary Hyperparathyroidism

Intervention / Treatment
-----------------
* Drug: Cinacalcet HCl
* Dietary Supplement: Standard of Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 6 - < 18 years Diagnosis of SHPT with the mean of the two consecutive central laboratory iPTH values ≥ 300 pg/mL during screening Corrected calcium value of ≥ 8.8 mg/dL during screening Diagnosis of CKD, receiving either hemodialysis or peritoneal dialysis, for ≥ 30 days prior to screening Parent or legally acceptable representative has provided written informed consent and subject has provided written assent when required by institutional guidelines Exclusion Criteria: 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 cytochrome P450 3A4 (CYP3A4) inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole) Use of concomitant medications that may prolong the QTc interval (eg, ondansetron, albuterol)

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care<br>Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders. | Dietary Supplement: Standard of Care<br>* Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.<br>|
| Experimental: Cinacalcet<br>In addition to standard of care participants received cinacalcet at a starting dose (based on dry body weight) of 0.20 mg/kg administered once a day by mouth. Dose adjustments and withholding were based on ionized calcium levels, plasma iPTH, and corrected calcium levels. | Drug: Cinacalcet HCl<br>* Capsules were opened and either sprinkled onto soft food (≥ 5 mg dose) or suspended into a sucrose syrup (≥ 2.5 mg dose) to create a liquid suspension for administration. Tablets were used for doses of 30 mg and higher in participants who could swallow tablets.<br>* Other names: Mimpara®;Dietary Supplement: Standard of Care<br>* Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a ≥ 30% Reduction From Baseline In Mean Plasma iPTH During Weeks 11 to 15 | Intact parathyroid hormone (iPTH) levels were measured at weeks 11 and 15; the mean value from these 2 measurements was calculated. This endpoint was the primary endpoint in the US only. | Baseline and weeks 11 to 15 | 
| Percentage of Participants Who Achieved a ≥ 30% Reduction From Baseline in Mean Plasma Intact Parathyroid Hormone During the Efficacy Assessment Period | Intact parathyroid hormone (iPTH) levels were measured at weeks 17, 18, 19 and 20; the mean value from these measurements was calculated. This endpoint was specified as the the primary endpoint in all countries except the United States (US). In the US this endpoint was specified as a secondary efficacy endpoint. | Baseline and the efficacy assessment period (EAP), weeks 17 to 20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieved a Mean iPTH ≤ 300 pg/mL (31.8 Pmol/L) During Weeks 17 to 20 |  | Efficacy assessment period, weeks 17 to 20 | 
| Percent Change in iPTH From Baseline to the Mean Value During Weeks 17 to 20 |  | Baseline and weeks 17 to 20 | 
| Change in Corrected Serum Calcium From Baseline to the Mean Value During Weeks 17 to 20 |  | Baseline and weeks 17 to 20 | 
| Change in Serum Phosphorus From Baseline to the Mean Value During Weeks 17 to 20 |  | Baseline and weeks 17 to 20 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Kidney Disease, Secondary Hyperparathyroidism, Dialysis, Pediatric