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

Phase 3

Terminated

• Conditions: Chronic Kidney Disease, Secondary Hyperparathyroidism
• Interventions: Drug: Cinacalcet HCl; Dietary Supplement: Standard of Care

• Registration Number: NCT02138838
• Lead Sponsor: Amgen

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.

Study Timeline

• Study First Submitted: 2014-04-01
• Study First Submitted QC: 2014-05-14
• Study First Posted: 2014-05-15
• Study Start: 2014-11-07
• Primary Completion: 2016-06-23
• Study Completion: 2016-06-23
• Disposition First Submitted: 2017-04-20
• Disposition First Submitted QC: 2017-04-20
• Disposition First Posted: 2017-04-24
• Results First Submitted: 2017-07-13
• Results First Submitted QC: 2017-08-16
• Results First Posted: 2017-09-14
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-12
• Last Update Posted: 2020-06-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 55

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cinacalcet	Cinacalcet HCl	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.
Standard of Care	Standard of Care	Standard of care therapy included the use of vitamin D sterols, calcium supplementation, and phosphate binders.
Cinacalcet	Standard of Care	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved a ≥ 30% Reduction From Baseline In Mean Plasma iPTH During Weeks 11 to 15	Baseline and 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.
Percentage of Participants Who Achieved a ≥ 30% Reduction From Baseline in Mean Plasma Intact Parathyroid Hormone During the Efficacy Assessment Period	Baseline and the efficacy assessment period (EAP), weeks 17 to 20	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.

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Research Site; 🇺🇦 Kyiv, Ukraine