Pediatric Chronic Kidney Disease Safety and Efficacy - Full Text View

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:

MedlinePlus related topics: Kidney Diseases

Drug Information available for: Cinacalcet Cinacalcet hydrochloride

U.S. FDA Resources

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.

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

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Sponsors and Collaborators

Amgen

Investigators


Study Director:	MD	Amgen

More Information

Additional Information:

AmgenTrials clinical trials website This link exits the ClinicalTrials.gov site


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 September 23, 2016