| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Secondary hyperparathyroidism in pediatric subjects with chronic kidney disease receiving hemodialysis or peritoneal dialysis |
|
| E.1.1.1 | Medical condition in easily understood language |
Chronic Kidney Disease
Hyperparathyroidism, Secondary
|
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10020708 |
| E.1.2 | Term | Hyperparathyroidism secondary |
| E.1.2 | System Organ Class | 10014698 - Endocrine disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To characterize corrected serum calcium levels on treatment with cinacalcet in pediatric subjects with secondary hyperparathyroidism |
|
| E.2.2 | Secondary objectives of the trial |
To characterize the pharmacokinetics in pediatric subjects
To characterize the pharmacodynamics in pediatric subjects |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Optional pharmacokinetics sub-study.
At week 24, if appropriate consent/assent has been obtained for the subject to participate in an optional PK assessment sub-study, the subject will have a PK
assessment over a 24 hour period in order to collect 10 PK samples. |
|
| E.3 | Principal inclusion criteria |
Subjects between the ages of 28 days to < 6 years of age at enrollment
Diagnosed with CKD and SHPT undergoing either HD or PD at the time of
screening (subjects 6 months or older should have been receiving
dialysis for ≥ 1 month)
Screening plasma iPTH level > 300 pg/mL (31.8 pmol/L) from the
central laboratory
Screening corrected calcium from the central laboratory:
- 9.4 mg/dL (2.35 mmol/L) for subjects aged 28 days to < 2 years
- 8.8 ( 2.2 mmol/L) for subjects aged 2 to < 6 years
Serum phosphorus from the central laboratory:
- 5.0 mg/dL (1.25 mmol/L) if age 28 days to < 1 year
- 4.5 mg/dL (1.13 mmol/L) if age 1 year to < 6 years
SHPT not due to vitamin D deficiency, per investigator assessment
Dialysate calcium level ≥ 2.5 mEq/L during screening
Subjects on anti-convulsant medication must be on a stable dose and
have a therapeutic blood level of the anti-convulsant at time of screening
Subject or subject's legally acceptable representative has provided
informed consent, and subject has provided assent when required by
institutional guidelines
Dry weight ≥ 7 kg at the time of screening |
|
| E.4 | Principal exclusion criteria |
A new onset of seizure or worsening of a pre-existing seizure disorder within 2 months prior to first dose of IP
Received therapy with cinacalcet within 30 days prior to enrollment
Scheduled date for kidney transplantation from a known living donor that makes completion of the study unlikely
Anemia which in the judgment of the investigator makes it inadvisable to undergo sequential blood draws
Subjects aged 28 days to 6 months of age who were born prematurely at < 36 weeks gestational age
Unstable chronic heart failure (CHF) defined as worsening pulmonary edema or other signs and symptoms as per investigator assessment during screening
History of congenital long QT interval, second or third degree heart block, ventricular tachyarrythmias or other conditions which prolong the QT interval
Corrected QT Interval (QTc) > 500 ms, using Bazett’s formula, during screening
QTc > 450 to ≤ 500 ms, using Bazett’s formula, during screening, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist
Any evidence of active malignancy
Either new or recurrent cardiac ventricular arrhythmias requiring a change in treatment within 10 days prior to screening or enrollment
Any unstable medical condition or unacceptable physical findings which in the judgment of the investigator precludes enrollment in this study
Hepatic impairment indicated by elevated levels of hepatic transaminase or bilirubin (aspartate aminotransferase (AST) ≥ 1.5 x upper limit of normal (ULN) OR alanine aminotransferase (ALT) ≥ 1.5 x ULN OR total bilirubin ≥ 1 x ULN per institutional laboratory range) at screening or Day 1
Known hypersensitivity to cinacalcet or any of the excipients in cinacalcet
Use of grapefruit juice, herbal medications or potent CYP 3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole) or, CYP2D6 substrates (e.g., flecainide, propafenone, metoprolol, desipramine, nortriptyline, clomipramine) within the 14 days prior to enrollment and during the study
Use of concomitant medications that may prolong the corrected QT interval (eg, ondansetron, albuterol), during screening
Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s)
Subject has previously been enrolled in this study
Subject will not be available for protocol required study visits or procedures, to the best of the subject and investigator's knowledge
Subject or subject's guardian has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject or guardian to give written informed consent and/or to comply with all required study procedures |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Proportion of subjects who develop corrected serum calcium levels < 9.0
mg/dL (2.25 mmol/L) for ages 28 days to < 2 years, and < 8.4 mg/dL
(2.1 mmol/L) for ages ≥ 2 to < 6 years |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| End of Study (The time when the last subject completes the last study visit assessment) |
|
| E.5.2 | Secondary end point(s) |
1)Proportion of subjects who develop corrected serum calcium levels <
8.8 mg/dL (2.2 mmol/L) during the study
2) PK parameters at Week 12 (eg, maximum plasma concentration
(Cmax), area under the curve (AUC), apparent clearance (CL/F),
apparent volume of distribution (V/F))
3) The percent change of plasma intact parathyroid hormone (iPTH),
corrected total serum calcium, serum phosphorus, and Ca x P from
baseline to scheduled visits during the study
4) Proportion of subjects who have any decreases in IPTH of > 30%
from baseline at two consecutive measurements
5) Achievement of plasma iPTH values between 200 and 300 pg/mL
(21.2 and 31.8 pmol/L) at any 2 consecutive measurements
6) Proportion of subjects who have any normal iPTH values between 200
and 300 pg/mL at two consecutive measurements
7) Safety Endpoints:
• Nature, frequency, severity, and relationship to treatment of all
adverse events, including those of special interest (as defined in Section
10.5.2.3, including hypocalcemia, seizures, and infections), reported
during the study
• Changes in laboratory parameters, including clinical chemistry, at
scheduled visits.
Subject incidence of hypocalcemia throughout the study
Changes in vital signs at scheduled visits
Electrocardiograms (ECGs) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) End of Study (The time when the last subject completes the last study visit assessment)
2)Week 12 and week 24 for subjects participating to the PK sub-study
3)Each study visit
4-7) End of Study (The time when the last subject completes the last study visit assessment) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Mexico |
| New Zealand |
| Russian Federation |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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