Back to resultsCinacalcet in Paediatric Secondary Hyperparathyroidism (SHPT) Due to Chronic Kidney Disease (CKD)
Primary Purpose
Secondary Hyperparathyroidism
Status
Unknown status
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Cinacalcet HCl
Sponsored by
About this trial
This is an interventional treatment trial for Secondary Hyperparathyroidism focused on measuring Cinacalcet, PK, Secondary Hyperparathyroidism, Paediatric, Chronic Kidney Disease, Dialysis
Eligibility Criteria
Inclusion Criteria:
- Parents'/guardian written informed consent, and child's assent
- Age > 2 and <18 years;
- A dry body weight (BW) >10.49 Kg in males and >9.95 Kg in females, respectively;
- Inpatient or outpatient status at the time of enrolment;
- Males or females. Female subjects sexually active must be neither pregnant nor breastfeeding, and must lack childbearing potential from screening visit to the end of the safety follow-up
- On stable hemodialysis (HD) or peritoneal dialysis (PD) for their CKD for at least one month before entering the 6-month pre-treatment period;
- Plasma iPTH levels > 300 pg/mL, AND
- Plasma Ca levels > 9.4 mg/dL (with normal serum albumin level), AND
- Plasma P levels <6.5 mg/dL in patients younger than 6 years, or <6.0mg/dL in older patients, OR
- Ca x P product > 60;
- Records' availability for the following parameters 6 months prior to study entry: demographic information, physical examination, height and dry weight, auxological/anthropometric indices, blood pressure values, Kt/V urea, plasma iPTH, calcium, phosphorus, and alkaline phosphatise levels, blood pH and bicarbonate, serum creatinine/urea, C reactive protein (CRP) levels, liver function tests, blood count, blood 25(OH) vitamin D3 level.
Exclusion Criteria:
- The following laboratory values: Hb<9.0 g/dL, WBC<2000/mm3 (2x109/L), platelets <150,000/mm3 (150x109/L) only in subjects who are otherwise eligible for PK/PD assessments; abnormal liver function, defined by a total bilirubin ≥2 times the upper limit of normal values, ASAT, ALAT, γ-GT levels ≥2 times the ULN values.
- Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study.
- History of malignancy (active malignancy, or off therapy since less than 1 year)
- History of diseases causing hypercalcemia
- Chronic inflammatory diseases (C-Reactive Protein-CRP >2 times the upper limit of normal values) requiring a concomitant corticosteroid or immunosuppressive therapy
- History of infectious diseases (including opportunistic infections) within 4 weeks prior to study entry
- Evidence as assessed by the Investigator of active or latent bacterial, viral or fungal infections at the time of potential enrollment, including subjects with evidence of HIV infection.
- Hepatitis-B surface antigen-positive subjects only in subjects who are otherwise eligible for PK/PD assessments
- Hepatitis C antibody-positive subjects who are also PCR-positive or RIBA positive only in subjects who are otherwise eligible for PK/PD assessments
- Use of recombinant human growth hormone therapy
- Use of drugs that interact with cinacalcet disposition
- Previous use of cinacalcet
Sites / Locations
- U.O. Nefrologia e Dialisi- Ospedale Giovanni XXIII
- U.O. Nefrologia e Dialisi - Istituto di Ricovero e Cura a Carattere Scientifico Giannina GasliniRecruiting
- U.O. Nefrologia e Dialisi Pediatrica - Clinica De Marchi
- U.O. Nefrologia e Dialisi - Ospedale Santobono
- U.O. Nefrologia e Dialisi - Ospedale Bambino Gesù
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
cinacalcet tab or extemporaneous solution po added to SoC
Arm Description
Subjects who meet all inclusion/exclusion criteria at baseline will be given cinacalcet 30mg film-coated tablet, for oral use added to phosphate binders and vitamin D analogue. For subjects receiving a cinacalcet dose <30mg, commercially available cinacalcet 30mg tab will be ground and diluted with a 5% dextrose solution. Then, an aliquot of this solution corresponding to the individually prescribed dose will be administered as indicated. Initial dosing of cinacalcet will be 0.5-0.75mg/kg or 30 mg po once daily (OD) each evening with food. During the cinacalcet dose-titration 6-month period for efficacy assessment, the dose will be increased on monthly basis by 0.5 mg/kg or by 30mg OD to achieve the target iPTH value <180 pg/mL, as tolerated by the subject, up to maximum of 180mg OD in absence of signs of hypocalcemia, according to the current summary of product characteristics.
Outcomes
Primary Outcome Measures
Composite EP, e.g. the proportion of patients who will have a reduction from baseline of >= 25% in mean iPTH levels with concomitant values for plasma P <6 mg/dL and Ca between 8.4 and 10.5 mg/dL or the Ca x P product <60
This composite EP will address the needed information on the appropriate dose of cinacalcet to be adopted in paediatric patients, and especially in younger children, as well as on the impact of treatment with calcimimetics on serum Ca and P levels, and on SHPT control over the long term
Secondary Outcome Measures
The long term control of iPTH level < 300 pg/mL
The long term control of PTH, Ca, P, and the Ca x P product values
The PK/ PD ( iPTH and testosterone) profile at individual patient level
The long term auxological indices and patient growth velocity during cinacalcet treatment
The proportion of patients with treatment-emergent adverse events (AEs), serious AEs (SAEs), and laboratory abnormalities over long term
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01479088
Brief Title
Cinacalcet in Paediatric Secondary Hyperparathyroidism (SHPT) Due to Chronic Kidney Disease (CKD)
Official Title
Twelve-month, Multicenter, Intra-subject Controlled (Retrospective-prospective), Open-label, Active-treatment Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics (PK) of Cinacalcet Hydrochloride for the Treatment of Secondary Hyperparathyroidism (SHPT) in Paediatric Subjects With Chronic Kidney Disease (CKD) on Dialysis, Followed by 12-month Study Extension.
Study Type
Interventional
2. Study Status
Record Verification Date
November 2011
Overall Recruitment Status
Unknown status
Study Start Date
March 2010 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
December 2013 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
ENRICO VERRINA
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Twelve-month, multicenter, intra-subject controlled (retrospective-prospective), open-label, active-treatment study to evaluate the dose-response and pharmacokinetics (PK) of cinacalcet HCl for the treatment of Secondary Hyperparathyroidism (SHPT) in paediatric subjects with chronic kidney disease (CKD) on dialysis, followed by 12-month study extension.
Detailed Description
This multicenter, intra-subject controlled, open-label, active-treatment study will assess in children affected by Secondary Hyperparathyroidism, aged 2-18 years on chronic dialysis not responsive to standard of care (SoC) therapy, the response after 6-month cinacalcet compared intra-subject to SoC alone at screening visit 6 months prior to cinacalcet start. Secondary objectives are to evaluate effects on growth over 18 months and PK profile. At baseline children have PTH levels>300 pg/mL, plasma P<6 mg/dL, and Ca 8.4-10.5 mg/dL, or Ca x P product>60 not responsive to SoC. Initial dosing of cinacalcet will be 0.5-0.75 mg/Kg per os OD to be adjusted up to a max of 180mg OD for target PTH values<180 pg/mL in absence of hypocalcemia. Thirty children will be enrolled at 12 centres participating in a national paediatric dialysis registry, corresponding to an α=0.05 and a power of 80% using the McNemar test, with an expected % of responders to cinacalcet or SoC of 40% or 5% respectively, with a drop-out rate of 15. Primary study endpoint (EP) will be the % of children who will have a reduction from baseline >25% in mean PTH levels during the 6-mo efficacy-assessment period. Among secondary EPs over 18 mos will be the % of patients with mean PTH levels<300 pg/mL; the % change in PTH, Ca, P values, and the Ca x P product; PK profile (or population profile by age) and its correlation with PTH and testosterone levels; auxological indices and growth velocity; % of children with treatment-emergent adverse events and lab abnormalities; retention on treatment and reasons of treatment withdrawal. The study will evaluate whether cinacalcet represents a safe and effective therapeutic option for SHPT children.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Secondary Hyperparathyroidism
Keywords
Cinacalcet, PK, Secondary Hyperparathyroidism, Paediatric, Chronic Kidney Disease, Dialysis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
cinacalcet tab or extemporaneous solution po added to SoC
Arm Type
Experimental
Arm Description
Subjects who meet all inclusion/exclusion criteria at baseline will be given cinacalcet 30mg film-coated tablet, for oral use added to phosphate binders and vitamin D analogue.
For subjects receiving a cinacalcet dose <30mg, commercially available cinacalcet 30mg tab will be ground and diluted with a 5% dextrose solution. Then, an aliquot of this solution corresponding to the individually prescribed dose will be administered as indicated.
Initial dosing of cinacalcet will be 0.5-0.75mg/kg or 30 mg po once daily (OD) each evening with food.
During the cinacalcet dose-titration 6-month period for efficacy assessment, the dose will be increased on monthly basis by 0.5 mg/kg or by 30mg OD to achieve the target iPTH value <180 pg/mL, as tolerated by the subject, up to maximum of 180mg OD in absence of signs of hypocalcemia, according to the current summary of product characteristics.
Intervention Type
Drug
Intervention Name(s)
Cinacalcet HCl
Other Intervention Name(s)
Mimpara®
Intervention Description
The 6-month pre-treatment period will be followed by a run-in period with a baseline evaluation prior to the drug administration, followed by a 6-month cinacalcet dose titration period, during which the dose will be increased on monthly basis by 0.5 mg/kg or by 30 mg OD up to the achievement of target iPTH value <180 pg/mL as tolerated by the patient
Primary Outcome Measure Information:
Title
Composite EP, e.g. the proportion of patients who will have a reduction from baseline of >= 25% in mean iPTH levels with concomitant values for plasma P <6 mg/dL and Ca between 8.4 and 10.5 mg/dL or the Ca x P product <60
Description
This composite EP will address the needed information on the appropriate dose of cinacalcet to be adopted in paediatric patients, and especially in younger children, as well as on the impact of treatment with calcimimetics on serum Ca and P levels, and on SHPT control over the long term
Time Frame
6 months
Secondary Outcome Measure Information:
Title
The long term control of iPTH level < 300 pg/mL
Time Frame
18 months
Title
The long term control of PTH, Ca, P, and the Ca x P product values
Time Frame
18 months
Title
The PK/ PD ( iPTH and testosterone) profile at individual patient level
Time Frame
12 months
Title
The long term auxological indices and patient growth velocity during cinacalcet treatment
Time Frame
18 months
Title
The proportion of patients with treatment-emergent adverse events (AEs), serious AEs (SAEs), and laboratory abnormalities over long term
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Parents'/guardian written informed consent, and child's assent
Age > 2 and <18 years;
A dry body weight (BW) >10.49 Kg in males and >9.95 Kg in females, respectively;
Inpatient or outpatient status at the time of enrolment;
Males or females. Female subjects sexually active must be neither pregnant nor breastfeeding, and must lack childbearing potential from screening visit to the end of the safety follow-up
On stable hemodialysis (HD) or peritoneal dialysis (PD) for their CKD for at least one month before entering the 6-month pre-treatment period;
Plasma iPTH levels > 300 pg/mL, AND
Plasma Ca levels > 9.4 mg/dL (with normal serum albumin level), AND
Plasma P levels <6.5 mg/dL in patients younger than 6 years, or <6.0mg/dL in older patients, OR
Ca x P product > 60;
Records' availability for the following parameters 6 months prior to study entry: demographic information, physical examination, height and dry weight, auxological/anthropometric indices, blood pressure values, Kt/V urea, plasma iPTH, calcium, phosphorus, and alkaline phosphatise levels, blood pH and bicarbonate, serum creatinine/urea, C reactive protein (CRP) levels, liver function tests, blood count, blood 25(OH) vitamin D3 level.
Exclusion Criteria:
The following laboratory values: Hb<9.0 g/dL, WBC<2000/mm3 (2x109/L), platelets <150,000/mm3 (150x109/L) only in subjects who are otherwise eligible for PK/PD assessments; abnormal liver function, defined by a total bilirubin ≥2 times the upper limit of normal values, ASAT, ALAT, γ-GT levels ≥2 times the ULN values.
Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study.
History of malignancy (active malignancy, or off therapy since less than 1 year)
History of diseases causing hypercalcemia
Chronic inflammatory diseases (C-Reactive Protein-CRP >2 times the upper limit of normal values) requiring a concomitant corticosteroid or immunosuppressive therapy
History of infectious diseases (including opportunistic infections) within 4 weeks prior to study entry
Evidence as assessed by the Investigator of active or latent bacterial, viral or fungal infections at the time of potential enrollment, including subjects with evidence of HIV infection.
Hepatitis-B surface antigen-positive subjects only in subjects who are otherwise eligible for PK/PD assessments
Hepatitis C antibody-positive subjects who are also PCR-positive or RIBA positive only in subjects who are otherwise eligible for PK/PD assessments
Use of recombinant human growth hormone therapy
Use of drugs that interact with cinacalcet disposition
Previous use of cinacalcet
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Enrico E. Verrina, MD
Phone
+390105636276
Email
enricoverrina@ospedale-gaslini.ge.it
First Name & Middle Initial & Last Name or Official Title & Degree
Ornella Della Casa Alberighi, MD PhD
Phone
+390105636461
Email
ornelladellacasa@ospedale-gaslini.ge.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Enrico E. Verrina, MD
Organizational Affiliation
U.O. Nefrologia e Dialisi; Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini
Official's Role
Principal Investigator
Facility Information:
Facility Name
U.O. Nefrologia e Dialisi- Ospedale Giovanni XXIII
City
Bari
ZIP/Postal Code
70100
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
U.O. Nefrologia e Dialisi - Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini
City
Genoa
ZIP/Postal Code
16147
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Enrico E Verrina, MD
Phone
+390105636276
Email
enricoverrina@ospedale-gaslini.ge.it
First Name & Middle Initial & Last Name & Degree
Ornella Della Casa Alberighi, MD PhD
Phone
+390105636461
Email
ornelladellacasa@ospedale-gaslini.ge.it
First Name & Middle Initial & Last Name & Degree
Enrico E. Verrina, MD
Facility Name
U.O. Nefrologia e Dialisi Pediatrica - Clinica De Marchi
City
Milan
ZIP/Postal Code
20100
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
U.O. Nefrologia e Dialisi - Ospedale Santobono
City
Naples
ZIP/Postal Code
80100
Country
Italy
Individual Site Status
Active, not recruiting
Facility Name
U.O. Nefrologia e Dialisi - Ospedale Bambino Gesù
City
Rome
ZIP/Postal Code
00100
Country
Italy
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Citations:
PubMed Identifier
16247644
Citation
Klaus G, Watson A, Edefonti A, Fischbach M, Ronnholm K, Schaefer F, Simkova E, Stefanidis CJ, Strazdins V, Vande Walle J, Schroder C, Zurowska A, Ekim M; European Pediatric Dialysis Working Group (EPDWG). Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines. Pediatr Nephrol. 2006 Feb;21(2):151-9. doi: 10.1007/s00467-005-2082-7. Epub 2005 Oct 25.
Results Reference
background
PubMed Identifier
18288502
Citation
Silverstein DM, Kher KK, Moudgil A, Khurana M, Wilcox J, Moylan K. Cinacalcet is efficacious in pediatric dialysis patients. Pediatr Nephrol. 2008 Oct;23(10):1817-22. doi: 10.1007/s00467-007-0742-5. Epub 2008 Feb 21.
Results Reference
background
PubMed Identifier
18504621
Citation
Muscheites J, Wigger M, Drueckler E, Fischer DC, Kundt G, Haffner D. Cinacalcet for secondary hyperparathyroidism in children with end-stage renal disease. Pediatr Nephrol. 2008 Oct;23(10):1823-9. doi: 10.1007/s00467-008-0810-5. Epub 2008 May 27.
Results Reference
background
PubMed Identifier
19838738
Citation
Platt C, Inward C, McGraw M, Dudley J, Tizard J, Burren C, Saleem MA. Middle-term use of Cinacalcet in paediatric dialysis patients. Pediatr Nephrol. 2010 Jan;25(1):143-8. doi: 10.1007/s00467-009-1294-7. Epub 2009 Oct 17.
Results Reference
background
PubMed Identifier
15558528
Citation
Harris RZ, Padhi D, Marbury TC, Noveck RJ, Salfi M, Sullivan JT. Pharmacokinetics, pharmacodynamics, and safety of cinacalcet hydrochloride in hemodialysis patients at doses up to 200 mg once daily. Am J Kidney Dis. 2004 Dec;44(6):1070-6. doi: 10.1053/j.ajkd.2004.08.029.
Results Reference
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PubMed Identifier
18783302
Citation
Padhi D, Harris RZ, Salfi M, Noveck RJ, Sullivan JT. Pharmacokinetics and pharmacodynamics of cinacalcet in hepatic impairment : phase I, open-label, parallel-group, single-dose, single-centre study. Clin Drug Investig. 2008;28(10):635-43. doi: 10.2165/00044011-200828100-00004.
Results Reference
background
PubMed Identifier
23222688
Citation
Cangemi G, Barco S, Verrina EE, Scurati S, Melioli G, Della Casa Alberighi O. Micromethod for quantification of cinacalcet in human plasma by liquid chromatography-tandem mass spectrometry using a stable isotope-labeled internal standard. Ther Drug Monit. 2013 Feb;35(1):112-7. doi: 10.1097/FTD.0b013e318278dc69.
Results Reference
derived
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Cinacalcet in Paediatric Secondary Hyperparathyroidism (SHPT) Due to Chronic Kidney Disease (CKD)
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