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

NCT01479088 | Unknown Phase 2 DMC

• 2 other identifiers: IGG_ev_0032009-016797-32
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

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.

Conditions

Secondary Hyperparathyroidism

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (5)

• The long term control of iPTH level < 300 pg/mL

  18 months

• The long term control of PTH, Ca, P, and the Ca x P product values

  18 months

• The PK/ PD ( iPTH and testosterone) profile at individual patient level

  12 months

• The long term auxological indices and patient growth velocity during cinacalcet treatment

  18 months

• The proportion of patients with treatment-emergent adverse events (AEs), serious AEs (SAEs), and laboratory abnormalities over long term

  18 months

Study Arms (1)

cinacalcet tab or extemporaneous solution po added to SoC

EXPERIMENTAL

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.

Drug: Cinacalcet HCl

Interventions

Cinacalcet HCl 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

Also known as: Mimpara®

cinacalcet tab or extemporaneous solution po added to SoC

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• ENRICO VERRINA: lead

Study Sites (5)

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

Genoa, Italy, 16147, Italy

RECRUITING

U.O. Nefrologia e Dialisi- Ospedale Giovanni XXIII

Bari, 70100, Italy

ACTIVE NOT RECRUITING

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

Related Publications (7)

• 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.

  PMID: 16247644 BACKGROUND

• 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.

  PMID: 18288502 BACKGROUND

• 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.

  PMID: 18504621 BACKGROUND

• 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.

  PMID: 19838738 BACKGROUND

• 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.

  PMID: 15558528 BACKGROUND

• 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.

  PMID: 18783302 BACKGROUND

• 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.

  PMID: 23222688 DERIVED

Related Links

• study description on the Italian Paediatric Nephrology Society website

MeSH Terms

Conditions

Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic

Interventions

Cinacalcet

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Enrico E. Verrina, MD

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Enrico E. Verrina, MD

CONTACT

+390105636276; enricoverrina@ospedale-gaslini.ge.it

Ornella Della Casa Alberighi, MD PhD

CONTACT

+390105636461; ornelladellacasa@ospedale-gaslini.ge.it

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Dialysis Unit

Study Record Dates

• First Submitted: November 22, 2011
• First Posted: November 24, 2011
• Study Start: March 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: November 24, 2011

Record last verified: 2011-11

Locations

IT (5)