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 | 18.0 |
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 SHPT |
|
E.2.2 | Secondary objectives of the trial |
- To characterize the pharmacokinetics (PK) in pediatric subjects
- To characterize the pharmacodynamics (PD) in pediatric subjects |
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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, who have 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, and not have received any cinacalcet therapy for at least 30 days prior to start of dosing
- Screening corrected total serum calcium from the central laboratory:
- ≥ 9.4 mg/dL (2.35 mmol/L) if age 28 days to < 2 years
- ≥ 8.8 mg/dL (2.2 mmol/L) if age ≥ 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 to < 6 years
- SHPT not due to vitamin D deficiency, per investigator assessment
- Dry weight ≥ 7 kg at the time of screening |
|
E.4 | Principal exclusion criteria |
- History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrhythmias or other conditions associated with prolonged QT interval
- Corrected QT interval (QTc) > 500 ms, using Bazett’s formula
- QTc ≥450 to ≤ 500 ms, using Bazett’s formula, unless written permission to enroll is provided by the investigator after consultation with a pediatric cardiologist
- Use of grapefruit juice, herbal medications, CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole), or CYP2D6 substrates (eg, flecainide, propafenone, metoprolol, desipramine, nortriptyline, clomipramine)
- Use of concomitant medications that may prolong the QTc interval (eg, ondansetron, albuterol) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Occurrence of 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 during the study |
|
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. Occurrence of corrected serum calcium < 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 iPTH, corrected total serum calcium, serum phosphorous, and Ca x P from baseline to scheduled visits during the study
4. Achievement of ≥ 30% reduction from baseline in plasma iPTH during the study
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. Achievement of plasma iPTH values < 300 pg/mL (31.8 pmol/L) during the study
7. Safety endpoints:
- Nature, frequency, severity, and relationship to treatment of all adverse events, including those of special interest, reported during the study
- Changes in laboratory parameters, including clinical chemistry, at scheduled visits |
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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) End of Study
5) Each study visit
6) End of study
7) Each study visit |
|
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 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
Mexico |
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
|
The time when the last subject completes the last study visit assessment. |
|
E.8.9 Initial estimate of the duration of the trial |
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 | 10 |