Trial Title:
Cinacalcet in Paediatric Secondary Hyperparathyroidism (SHPT) Due to Chronic Kidney Disease (CKD)
NCT ID:
NCT01479088
Condition:
Secondary Hyperparathyroidism
Conditions: Official terms:
Neoplasm Metastasis
Kidney Diseases
Renal Insufficiency, Chronic
Hyperparathyroidism
Hyperparathyroidism, Secondary
Cinacalcet
Conditions: Keywords:
Cinacalcet
PK
Secondary Hyperparathyroidism
Paediatric
Chronic Kidney Disease
Dialysis
Study type:
Interventional
Study phase:
Phase 2/Phase 3
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Cinacalcet HCl
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
Arm group label:
cinacalcet tab or extemporaneous solution po added to SoC
Other name:
Mimpara®
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.
Criteria for 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
Gender:
All
Minimum age:
2 Years
Maximum age:
18 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
U.O. Nefrologia e Dialisi- Ospedale Giovanni XXIII
Address:
City:
Bari
Zip:
70100
Country:
Italy
Status:
Active, not recruiting
Facility:
Name:
U.O. Nefrologia e Dialisi - Istituto di Ricovero e Cura a Carattere Scientifico Giannina Gaslini
Address:
City:
Genoa
Zip:
16147
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Enrico E Verrina, MD
Phone:
+390105636276
Email:
enricoverrina@ospedale-gaslini.ge.it
Contact backup:
Last name:
Ornella Della Casa Alberighi, MD PhD
Phone:
+390105636461
Email:
ornelladellacasa@ospedale-gaslini.ge.it
Investigator:
Last name:
Enrico E. Verrina, MD
Email:
Principal Investigator
Facility:
Name:
U.O. Nefrologia e Dialisi Pediatrica - Clinica De Marchi
Address:
City:
Milan
Zip:
20100
Country:
Italy
Status:
Active, not recruiting
Facility:
Name:
U.O. Nefrologia e Dialisi - Ospedale Santobono
Address:
City:
Naples
Zip:
80100
Country:
Italy
Status:
Active, not recruiting
Facility:
Name:
U.O. Nefrologia e Dialisi - Ospedale Bambino Gesù
Address:
City:
Rome
Zip:
00100
Country:
Italy
Status:
Active, not recruiting
Start date:
March 2010
Completion date:
December 2013
Lead sponsor:
Agency:
ENRICO VERRINA
Agency class:
Other
Source:
Istituto Giannina Gaslini
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01479088
