E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary hyperparathyroidism (HPT) in subjects with chronic kidney
disease (CKD) receiving maintenance hemodialysis. |
|
E.1.1.1 | Medical condition in easily understood language |
Secondary hyperparathyroidism |
|
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 | 17.1 |
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 evaluate the safety and tolerability of cinacalcet HCl after single
administration to pediatric patients aged 28 days to < 6 years with CKD
receiving dialysis |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the PK of cinacalcet HCl after single administration to
pediatric patients aged 28 days to < 6 years with CKD receiving dialysis
• To evaluate pharmacodynamic (PD) parameters of plasma intact
parathyroid hormone (iPTH), serum calcium (total calcium, albumin
corrected calcium and ionized calcium) following single administration of
cinacalcet HCl to pediatric patients aged 28 days to < 6 years with CKD
receiving dialysis.
• To evaluate correlations of PK parameters and age, weight and body
surface area
• To evaluate correlations of PK parameters and PD parameters |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
General
Subject's parent, or legally acceptable guardian, must sign an
Independent Ethics Committee (IEC) or Institutional Review Board (IRB)
approved Informed Consent Form (ICF). At the discretion of the
investigator, subject assent may also be obtained.
Disease Related
Subjects 28 days to < 6 years of age with CKD and secondary
hyperparathyroidism (sHPT) as diagnosed by principal investiators,
undergoing hemodialysis or peritoneal dialysis at the time of screening (subjects 6 months or older should have been receiving dialysis for ≥ 2 months) and who have not received any cinacalcet HCl therapy for at least 2 weeks prior to dosing on Day 1
Free of any disease or condition (other than those diseases or conditions
related to their renal disease, that, in the opinion of the investigator,
would impact the subject's safety or the integrity of the study data)
Demographic
Must weigh ≥ 6 kg at screening and at Day-1
Must be at least 30 weeks of gestational age
Physical examination must be acceptable to the investigator at screening and at Day-1
Laboratory
Hemoglobin ≥ 8 g/dL at screening and at Day-1
Serum calcium within normal ranges at screening and at Day-1
Normal or clinically acceptable ECG (12-lead reporting RR, PR, QRS, and
QT intervals) at screening and at Day-1
Clinical laboratory tests that are acceptable to the investigator at
screening and at Day -1 |
|
E.4 | Principal exclusion criteria |
Disease Related
Current or historic malignancy
Cardiac ventricular arrhythmias within 28 days prior to screening
A gastrointestinal disorder or surgery that could affect the absorption of drugs (eg, pyloric stenosis or any gut-shortening surgical procedure
prior to screening)
History of seizure
History of prolongation of the QT interval
Corrected QT Interval (QTc) > 500 ms during screening, using Bazett's
Formula
QTc ≥ 450 and ≤ 500 ms during screening, using Bazett's formula
Concurrent or within 28 days prior to enrollment use of medications that prolong QT interval
Major surgery (defined as any surgical procedure that involves general
anesthesia or respiratory assistance) within 28 days prior to screening.
Laboratory
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
Medications
Known hypersensitivity to cinacalcet HCl or any of the excipients in
cinacalcet HCl
Use of grapefruit juice, herbal medications or potent CYP 3A4 inhibitors
(eg, erythromycin, clarithromycin, ketokonazole, itraconazole) within the 14 days prior to enrollment and during the study
Concurrent or within 28 days prior to enrollment use of medications that are predominantly metabolized by the enzyme CYP2D6 and have a
narrow therapeutic index (eg, flecainide, vinblastine, thioridazine,
tricyclic antidepressants such as desipramine and imipramine, and betablockers such as metoprolol or carvedilol)
General
Subjects who have participated in a clinical trial of an investigational
drug/or device within 90 days prior to enrollment
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Treatment-emergent adverse events, including clinically significant
changes in physical examinations, laboratory safety tests,
electrocardiograms (ECG), and vital signs |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
AEs: Screening, day -1, pre-dose, at 0, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours
post-dose, days 2, 3, 4 and 7.
Physical examinations: Screening, day -1 and day 4
Laboratory tests: Screening, Day -1, at 2 hours post dose and Day 3. In
addition, subjects will be randomly assigned to an 8 hour or 12 hour post dose collection
ECGs: Screening, day -1 and day 4
Vital signs: Screening, day -1, pre-dose, days 2, 3 and 4. |
|
E.5.2 | Secondary end point(s) |
Rich sampling PK parameters of cinacalcet (AUC, Cmax, tmax and t½)
PD parameters of iPTH, and measurements of serum calcium (total
calcium, albumin corrected calcium and ionized calcium) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK at 0.5, 1, 2, 3, 4, 6, 8 and 12 hours post-dose, days 2, 3 and 4.
PD at Screening, day -1, 2 hours post-dose and Day 3. In addition,
subjects will be randomly assigned to an 8- or 12-hour post dose
collection. |
|
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 | No |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Single-dose safety, PK and PD study in children aged 28 Days to < 6 Years |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
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 | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 |
|
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
|
Last patient, last end of study assessment |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 2 |
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 |