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

Information source: Istituto Giannina Gaslini
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Secondary Hyperparathyroidism

Intervention: Cinacalcet HCl (Drug)

Phase: Phase 2/Phase 3

Status: Recruiting

Sponsored by: ENRICO VERRINA

Official(s) and/or principal investigator(s):
Enrico E. Verrina, MD, Principal Investigator, Affiliation: U.O. Nefrologia e Dialisi; Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini

Overall contact:
Enrico E. Verrina, MD, Phone: +390105636276, Email: enricoverrina@ospedale-gaslini.ge.it

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.

Clinical Details

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 design: Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

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

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.

Eligibility

Minimum age: 2 Years. Maximum age: 18 Years. Gender(s): Both.

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

Locations and Contacts

Enrico E. Verrina, MD, Phone: +390105636276, Email: enricoverrina@ospedale-gaslini.ge.it

U.O. Nefrologia e Dialisi- Ospedale Giovanni XXIII, Bari 70100, Italy; Active, not recruiting

U.O. Nefrologia e Dialisi - Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini, Genoa 16147, Italy; Recruiting
Enrico E Verrina, MD, Phone: +390105636276, Email: enricoverrina@ospedale-gaslini.ge.it
Ornella Della Casa Alberighi, MD PhD, Phone: +390105636461, Email: ornelladellacasa@ospedale-gaslini.ge.it
Enrico E. Verrina, MD, Principal Investigator

U.O. Nefrologia e Dialisi Pediatrica - Clinica De Marchi, Milan 20100, Italy; Active, not recruiting

U.O. Nefrologia e Dialisi - Ospedale Santobono, Naples 80100, Italy; Active, not recruiting

U.O. Nefrologia e Dialisi - Ospedale Bambino Gesù, Rome 00100, Italy; Active, not recruiting

Additional Information

study description on the Italian Paediatric Nephrology Society website

Related publications:

Klaus G, Watson A, Edefonti A, Fischbach M, Rönnholm K, Schaefer F, Simkova E, Stefanidis CJ, Strazdins V, Vande Walle J, Schröder 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. Epub 2005 Oct 25.

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.

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.

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.

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.

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.

Starting date: March 2010
Last updated: November 23, 2011

Page last updated: August 23, 2015

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