cinacalcet in paediatric secondary hyperparathyroidism (shpt) due to chronic kidney disease (ckd)

Conditions: Secondary Hyperparathyroidism

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.

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\ 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\ 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 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

Keywords: cinacalcet pk secondary hyperparathyroidism paediatric chronic kidney disease dialysis