Cinacalcet in Paediatric Secondary Hyperparathyroidism (SHPT) Due to Chronic Kidney Disease (CKD)

NCT ID: NCT01479088

Last Updated: 2011-11-24

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-03-31
• Study Completion Date: 2013-12-31

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.

Conditions

Secondary Hyperparathyroidism

Keywords

Cinacalcet; PK; Secondary Hyperparathyroidism; Paediatric; Chronic Kidney Disease; Dialysis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

cinacalcet tab or extemporaneous solution po added to SoC

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.

Group Type: EXPERIMENTAL

Cinacalcet HCl

Intervention Type: DRUG

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

Interventions

Cinacalcet HCl

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

Intervention Type: DRUG

Other Intervention Names

Mimpara®

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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ENRICO VERRINA

OTHER

Sponsor Role: lead

Responsible Party

ENRICO VERRINA

Director of Dialysis Unit

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Enrico E. Verrina, MD

Role: PRINCIPAL_INVESTIGATOR

U.O. Nefrologia e Dialisi; Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini

Locations

U.O. Nefrologia e Dialisi - Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini

Genoa, Italy, Italy

Site Status: RECRUITING

U.O. Nefrologia e Dialisi- Ospedale Giovanni XXIII

Bari, , Italy

Site Status: ACTIVE_NOT_RECRUITING

U.O. Nefrologia e Dialisi Pediatrica - Clinica De Marchi

Milan, , Italy

Site Status: ACTIVE_NOT_RECRUITING

U.O. Nefrologia e Dialisi - Ospedale Santobono

Naples, , Italy

Site Status: ACTIVE_NOT_RECRUITING

U.O. Nefrologia e Dialisi - Ospedale Bambino Gesù

Rome, , Italy

Site Status: ACTIVE_NOT_RECRUITING

Countries

Italy

Central Contacts

Enrico E. Verrina, MD

Role: CONTACT

Phone: +390105636276

Email: enricoverrina@ospedale-gaslini.ge.it

Ornella Della Casa Alberighi, MD PhD

Role: CONTACT

Phone: +390105636461

Email: ornelladellacasa@ospedale-gaslini.ge.it

Facility Contacts

Enrico E Verrina, MD

Role: primary

Ornella Della Casa Alberighi, MD PhD

Role: backup

References

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.

Reference Type: BACKGROUND

PMID: 16247644 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18288502 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18504621 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19838738 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15558528 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18783302 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23222688 (View on PubMed)

Related Links

http://www.sinp.eu/index/index/atom/131

study description on the Italian Paediatric Nephrology Society website

Other Identifiers

2009-016797-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IGG_ev_003

Identifier Type: -

Identifier Source: org_study_id