Pediatric Chronic Kidney Disease Safety and Efficacy

This study has been terminated.
(Study was suspended in agreement between sponsor and FDA due to concerns about the study design after a fatality had occurred in the presence of hypocalcemia.)
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01277510
First received: January 13, 2011
Last updated: June 12, 2015
Last verified: May 2015
  Purpose
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.

Condition Intervention Phase
Chronic Kidney Disease
Hyperparathyroidism
Hyperparathyroidism, Secondary
Kidney Disease
Secondary Hyperparathyroidism
Drug: cinacalcet capsule
Drug: placebo
Drug: Standard of Care
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percentage of Participants Achieving ≥ 30% Reduction in Mean iPTH From Baseline to the Efficacy Assessment Phase [ Time Frame: From Baseline to the Efficacy Assessment Phase, Weeks 25-30 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants Achieving Mean iPTH ≤ 300 pg/mL (31.8 Pmol/L) During the Efficacy Assessment Phase [ Time Frame: From Baseline to the Efficacy Assessment Phase (EAP), Weeks 25-30 ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Mean Corrected Total Serum Calcium During the Efficacy Assessment Period [ Time Frame: From Baseline to the Efficacy Assessment Phase, Weeks 25-30. ] [ Designated as safety issue: No ]
    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."

  • Percent Change From Baseline in Mean Serum Phosphorus During the Efficacy Assessment Phase [ Time Frame: From Baseline to the Efficacy Assessment Phase, Weeks 25-30. ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Mean Phosphorous Product (Ca x P) During the Efficacy Assessment Phase [ Time Frame: From Baseline to end of Efficacy Assessment Period, assessed up to 30 weeks ] [ Designated as safety issue: No ]
    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.

  • Growth Velocity From Baseline to End of Double-blind Phase [ Time Frame: From Baseline to end of Efficacy Assessment at Week 30 ] [ Designated as safety issue: No ]
    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.

  • Growth Velocity From End of Double-blind Phase to End of Open-label Phase [ Time Frame: End of double-blind phase (Week 30) until end of the open-label phase (Week 60) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Mean Ionized Calcium During the Efficacy Assessment Phase [ Time Frame: From Baseline to the Efficacy Assessment Phase, Weeks 25-30. ] [ Designated as safety issue: No ]
    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.


Enrollment: 43
Study Start Date: June 2011
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: cinacalcet capsule
Cinacalcet was prepared for oral administration as both capsules for sprinkling and film coated tablets for swallowing.
Other Name: Sensipar, Mimpara
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.

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.
  Eligibility

Ages Eligible for Study:   6 Years to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01277510

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

Additional Information:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01277510     History of Changes
Other Study ID Numbers: 20070208 
Study First Received: January 13, 2011
Results First Received: April 29, 2015
Last Updated: June 12, 2015
Health Authority: European Union: EMEA
United States: Food and Drug Administration
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Hungary: National Institute of Pharmacy
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Federal Service for Surveillance in the field of Healthcare and Social Development (a body of the Ministry of Health)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Mexico: Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS)
Peru: Instituto Nacional de Salud (INS)
Brasil: ANVISA - Agência Nacional de Vigilância Sanitária ("National Agency of Sanitary Surveillance")
Argentina: ANMAT - Administración Nacional de Medicamentos, Alimentos y Tecnologia Médica ("National Drug Administration, Food and Medical Tecnology")

Keywords provided by Amgen:
dialysis
sensipar
mimpara
hemodialysis
peritoneal dialysis
renal
parathyroid hormone
pediatric

Additional relevant MeSH terms:
Kidney Diseases
Neoplasm Metastasis
Renal Insufficiency, Chronic
Hyperparathyroidism
Hyperparathyroidism, Secondary
Urologic Diseases
Neoplastic Processes
Neoplasms
Pathologic Processes
Renal Insufficiency
Parathyroid Diseases
Endocrine System Diseases
Cinacalcet Hydrochloride
Calcimimetic Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 24, 2016