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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
Results First Received: April 29, 2015  
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
Conditions: Chronic Kidney Disease
Hyperparathyroidism
Hyperparathyroidism, Secondary
Kidney Disease
Secondary Hyperparathyroidism
Interventions: Drug: cinacalcet capsule
Drug: placebo
Drug: Standard of Care

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

The first patient was enrolled on 28 June 2011 and the last patient enrolled was on 15 January 2013.

Eligible participants were between the ages of 6 to less than 18 years old who had chronic kidney (CKD) and secondary hyperparathyroidism treated with either hemodialysis or peritoneal dialysis for ≥ 2 months.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
This study consisted of a 30-week randomized, double-blind phase followed by a 30-week open-label phase. Participants were randomized 1:1 to receive either cinacalcet or placebo in the double-blind phase. All participants received cinacalcet in the open-label phase.

Reporting Groups
  Description
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.
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. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight.

Participant Flow for 2 periods

Period 1:   Double-blind Phase
    Placebo     Cinacalcet  
STARTED     21     22  
Received Investigational Product     21     22  
COMPLETED     8 [1]   4 [1]
NOT COMPLETED     13     18  
Non-compliance                 0                 1  
Adverse Event                 1                 0  
Withdrawal by Subject                 2                 0  
Administrative decision                 7                 9  
Death                 0                 1  
Protocol-specified criteria                 2                 6  
Other                 1                 1  
[1] Completed investigational product

Period 2:   Open-label Phase
    Placebo     Cinacalcet  
STARTED     8     4  
Received Investigational Product     6     4  
COMPLETED     1 [1]   1 [1]
NOT COMPLETED     7     3  
Administrative decision                 4                 3  
Protocol-specified criteria                 1                 0  
Never received investigational product                 2                 0  
[1] Completed investigational product



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
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.
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. Regardless of the titration level reached at the last dose of IP in the double-blind phase, all participants started titration at ≤ 0.20 mg/kg based on dry weight.
Total Total of all reporting groups

Baseline Measures
    Placebo     Cinacalcet     Total  
Number of Participants  
[units: participants]
  21     22     43  
Age  
[units: years]
Mean (Standard Deviation)
  13.2  (2.9)     13.3  (3.6)     13.2  (3.3)  
Age, Customized  
[units: participants]
     
6 to < 12 years     5     6     11  
12 to < 18 years     16     16     32  
Gender  
[units: participants]
     
Female     10     12     22  
Male     11     10     21  
Race/Ethnicity, Customized  
[units: participants]
     
White     15     16     31  
Black or African American     6     5     11  
Other     0     1     1  
Race/Ethnicity, Customized  
[units: participants]
     
Hispanic or Latino     5     3     8  
Not Hispanic or Latino     16     19     35  
Intact Parathyroid Hormone (iPTH)  
[units: pg/mL]
Mean (Standard Deviation)
  795.8  (537.9)     757.1  (440.1)     776.0  (484.8)  
Corrected Total Serum Calcium [1]
[units: mg/dL]
Mean (Standard Deviation)
  9.88  (0.62)     9.91  (0.54)     9.90  (0.58)  
Serum Phosphorous  
[units: mg/dL]
Mean (Standard Deviation)
  6.37  (1.48)     6.68  (1.78)     6.53  (1.63)  
[1]

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)).




  Outcome Measures
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1.  Primary:   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 ]

2.  Secondary:   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 ]

3.  Secondary:   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. ]

4.  Secondary:   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. ]

5.  Secondary:   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 ]

6.  Secondary:   Growth Velocity From Baseline to End of Double-blind Phase   [ Time Frame: From Baseline to end of Efficacy Assessment at Week 30 ]

7.  Secondary:   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) ]

8.  Secondary:   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. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was terminated early with a smaller sample size. However, the study was still sufficiently powered for the double-blind phase. The data collected in the open-label phase is very sparse.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436



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")