Pediatric Chronic Kidney Disease Safety and Efficacy

A Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of Cinacalcet HCl in Pediatric Subjects With Chronic Kidney Disease and Secondary Hyperparathyroidism Receiving Dialysis

The purpose of this study is to assess the safety and efficacy of adding cinacalcet to the current treatment of secondary hyperparathyroidism in children currently receiving dialysis compared to a treatment regimen that does not include cinacalcet.

Study Overview

• Status: Terminated
• Conditions: Hyperparathyroidism; Chronic Kidney Disease; Secondary Hyperparathyroidism; Hyperparathyroidism, Secondary; Kidney Disease
• Intervention / Treatment: Drug: placebo; Drug: Standard of Care; Drug: cinacalcet capsule

Detailed Description

Secondary hyperparathyroidism (SHPT) is a condition that can develop early in patients with chronic kidney disease (CKD), usually gets worse over time, and is known to cause problems for patients on dialysis. Children on dialysis can have a wide range of bone and growth issues, and common treatments have a chance of making these things worse by increasing serum calcium and serum phosphorus. Cinacalcet has been shown to be effective in controlling parathyroid hormone (PTH), calcium and phosphorus in adults. The purpose of this study is to show that including cinacalcet in the treatment of SHPT will lower the levels of intact parathyroid hormone (iPTH) in a larger number of pediatric patients with CKD who are receiving dialysis, compared to a treatment regimen that does not include cinacalcet.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Research Site
    • Westmead, New South Wales, Australia, 2145
      • Research Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Research Site
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Research Site
• Belgium
  • Bruxelles, Belgium, 1020
    • Research Site
  • Edegem, Belgium, 2650
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
• Germany
  • Heidelberg, Germany, 69120
    • Research Site
  • Marburg, Germany, 35043
    • Research Site
• Hungary
  • Budapest, Hungary, 1083
    • Research Site
  • Debrecen, Hungary, 4032
    • Research Site
  • Pecs, Hungary, 7623
    • Research Site
  • Szeged, Hungary, 6720
    • Research Site
• Mexico
  • Aguascalientes, Mexico, 20219
    • Research Site
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 04530
      • Research Site
• Poland
  • Gdansk, Poland, 80-952
    • Research Site
  • Gorzow Wielkopolski, Poland, 66-400
    • Research Site
  • Lodz, Poland, 93-338
    • Research Site
  • Warszawa, Poland, 04-730
    • Research Site
  • Warszawa, Poland, 00-576
    • Research Site
• Russian Federation
  • Moscow, Russian Federation, 107014
    • Research Site
  • Saint Petersburg, Russian Federation, 198205
    • Research Site
  • Samara, Russian Federation, 443095
    • Research Site
• Slovakia
  • Banska Bystrica, Slovakia, 974 09
    • Research Site
  • Bratislava, Slovakia, 833 40
    • Research Site
  • Kosice, Slovakia, 040 11
    • Research Site
• Spain
  • Madrid, Spain, 28046
    • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Research Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Research Site
  • PaÃ-s Vasco
    • Baracaldo, PaÃ-s Vasco, Spain, 48903
      • Research Site
  • País Vasco
    • Baracaldo, País Vasco, Spain, 48903
      • Research Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Research Site
  • California
    • Los Angeles, California, United States, 90095
      • Research Site
    • San Francisco, California, United States, 94143
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32610
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Research Site
    • Saint Louis, Missouri, United States, 63110
      • Research Site
    • Saint Louis, Missouri, United States, 63104
      • Research Site
  • New Jersey
    • Livingston, New Jersey, United States, 07039
      • Research Site
  • New York
    • Bronx, New York, United States, 10467
      • Research Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97227
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site
    • San Antonio, Texas, United States, 78229
      • Research Site
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 6 to less than 18 years at screening
• Diagnosed with CKD and SHPT receiving hemodialysis or peritoneal dialysis for ≥ 2 months before randomization
• Dry weight ≥ 12.5 kg at screening
• iPTH obtained from the central laboratory must be > 300 pg/mL (31.8 pmol/L)
• Serum calcium (corrected) obtained from the central laboratory must be ≥ 8.8 mg/dL (2.2 mmol/L)
• Serum phosphorus obtained from the central laboratory ≥ 4.0 mg/dL (1.3 mmol/L) for children 6 to less than 12 years old, or ≥ 3.5 mg/dL (1.1 mmol/L) for children 12 to less than 18 years old
• Subjects already receiving vitamin D sterols (either calcitriol or a synthetic analog), a stable dose within the last 2 months prior to randomization
• Subjects taking growth hormone, a stable dose defined as no change > than 20% in the last 2 months prior to randomization
• Subjects on anti-convulsant medication must be on a stable dose for 3 months, and have a therapeutic blood level of the anti-convulsant at the time of randomization
• Subjects must be on a dialysate calcium concentration of ≥ 2.5 mEq/L (1.25 mmol/L) for at least 2 months prior to randomization

Exclusion Criteria:

• Underwent parathyroidectomy in the last 6 months
• Anticipated parathyroidectomy within 6 months after randomization
• Received therapy with cinacalcet (sensipar/mimpara) within the last month
• A new onset of seizure or worsening of a pre-existing seizure disorder within the last 3 months
• Scheduled date for kidney transplant from a known living donor that makes completion of the study unlikely

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants received standard of care and placebo once daily for 30 weeks during the double-blind phase. During the open-label phase, participants received cinacalcet with standard of care for an additional 30 weeks. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks up to Week 54 to a maximum dose of 4.2 mg/kg.	Drug: placebo; Placebo tablets and capsules for sprinkling identical to active treatment.; Drug: Standard of Care; All participants, regardless of treatment assignment, will receive standard of care with vitamin D sterols (calcitriol and its analogs), as prescribed by the treating physician.
Experimental: Cinacalcet; Participants received standard of care and cinacalcet once daily for 30 weeks during the double-blind phase. The starting dose of cinacalcet was ≤ 0.20 mg/kg based on dry weight, and could be titrated up according to plasma iPTH and serum calcium levels every 4 weeks until Week 24 to a maximum dose of 4.2 mg/kg. During the open-label phase participants continued to receive cinacalcet with standard of care for an additional 30 weeks.	Drug: Standard of Care; All participants, regardless of treatment assignment, will receive standard of care with vitamin D sterols (calcitriol and its analogs), as prescribed by the treating physician.; Drug: cinacalcet capsule; Cinacalcet was prepared for oral administration as both capsules for sprinkling and film coated tablets for swallowing.; Other Names: Sensipar, Mimpara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving ≥ 30% Reduction in Mean iPTH From Baseline to the Efficacy Assessment Phase	The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase (EAP; Weeks 25 - 30). When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available post-baseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.	From Baseline to the Efficacy Assessment Phase, Weeks 25-30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Mean iPTH ≤ 300 pg/mL (31.8 Pmol/L) During the Efficacy Assessment Phase	The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.	From Baseline to the Efficacy Assessment Phase (EAP), Weeks 25-30
Percent Change From Baseline in Mean Corrected Total Serum Calcium During the Efficacy Assessment Period	Serum calcium was reported as a corrected value by the central laboratory based on calcium and albumin concentrations: Corrected total calcium (mg/dL) = measured total serum calcium (mg/dL) + 0.8 (4.0 - Serum albumin (g/dL)). The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used."	From Baseline to the Efficacy Assessment Phase, Weeks 25-30.
Percent Change From Baseline in Mean Serum Phosphorus During the Efficacy Assessment Phase	The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.	From Baseline to the Efficacy Assessment Phase, Weeks 25-30.
Percent Change From Baseline in Mean Phosphorous Product (Ca x P) During the Efficacy Assessment Phase	The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.	From Baseline to end of Efficacy Assessment Period, assessed up to 30 weeks
Growth Velocity From Baseline to End of Double-blind Phase	Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of double-blind phase visit was at Week 30 by design but the last assessment in the double-blind phase was used due to the early termination of the study.	From Baseline to end of Efficacy Assessment at Week 30
Growth Velocity From End of Double-blind Phase to End of Open-label Phase	Linear growth velocity (cm/year) = 52 x change in height (cm) / number of weeks between the two assessments. End of open-label phase visit was at Week 60 by design but the last assessment in the open-label phase was used due to the early termination of the study.	End of double-blind phase (Week 30) until end of the open-label phase (Week 60)
Percent Change From Baseline in Mean Ionized Calcium During the Efficacy Assessment Phase	The efficacy assessment value is based on the scheduled assessment(s) taken during the efficacy assessment phase. When multiple assessments were available, the average of those was used. If an efficacy measurement during the EAP was missing, the mean of the last 2 available postbaseline values in the dose-titration phase was used. If only one post-baseline value was available, this single value was used.	From Baseline to the Efficacy Assessment Phase, Weeks 25-30.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• 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 Sep;35(9):1679-1697. doi: 10.1007/s00467-020-04516-4. Epub 2020 May 4.
• Warady BA, Iles JN, Ariceta G, Dehmel B, Hidalgo G, Jiang X, Laskin B, Shahinfar S, Vande Walle J, Schaefer F. A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet in pediatric patients with chronic kidney disease and secondary hyperparathyroidism receiving dialysis. Pediatr Nephrol. 2019 Mar;34(3):475-486. doi: 10.1007/s00467-018-4116-y. Epub 2018 Nov 30.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2011
• Primary Completion (Actual): April 30, 2014

Study Registration Dates

• First Submitted: January 13, 2011
• First Submitted That Met QC Criteria: January 13, 2011
• First Posted (Estimate): January 17, 2011

Study Record Updates

• Last Update Posted (Actual): June 29, 2020
• Last Update Submitted That Met QC Criteria: June 12, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: renal; pediatric; dialysis; peritoneal dialysis; hemodialysis; parathyroid hormone; sensipar; mimpara
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Parathyroid Diseases; Neoplastic Processes; Kidney Diseases; Renal Insufficiency, Chronic; Hyperparathyroidism; Neoplasm Metastasis; Hyperparathyroidism, Secondary; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Calcimimetic Agents; Cinacalcet
• Other Study ID Numbers: 20070208