E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary Hyperparathyroidism and Chronic Kidney Disease Receiving
Dialysis |
|
E.1.1.1 | Medical condition in easily understood language |
Secondary Hyperparathyroidism and Chronic Kidney Disease |
|
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 the long-term safety and tolerability of cinacalcet in pediatric subjects with CKD receiving dialysis |
|
E.2.2 | Secondary objectives of the trial |
To characterize the long-term effect of cinacalcet in pediatric subjects receiving dialysis on laboratory parameters associated with CKD-MBD |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
101 Subject’s legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any day 1 study-specific activities/procedures being initiated.
102 Dialysate calcium concentration ≥ 2.5 mEq/L at day 1
All subjects from 20130356:
103 Completed treatment through week 20 in the 20130356 study
104 Dry weight ≥ 12.5 kg at day 1 of Study 20140159
Subjects Randomized to the 20130356 Standard of Care Arm Only
105 iPTH value ≥ 300 pg/mL (week 19 in 20130356)
106 Corrected calcium value ≥ 8.8 mg/dL (week 19 in 20130356)
All Subjects from 20110100
107 Completed Week 26 End of Study visit in the 20110100 study
108 Dry weight ≥ 7 kg at day 1 of Study 20140159 |
|
E.4 | Principal exclusion criteria |
General:
Studies 20130356 or 20110100
201 Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(s), other than Amgen Studies 20130356 or 20110100.
202 Other investigational procedures while participating in this study are excluded.
203 Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years.
204 Subject has known sensitivity to any of the products to be administered during dosing.
205 Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, electronic patient diary [ediary]) to the best of the subject and investigator’s knowledge
206 History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
207 Subject previously has entered this study.
208 If sexually active, subject is not willing to use highly effective contraception during treatment and for at least 9 days after the end of treatment
209 Subject is pregnant or breast feeding, or planning to become pregnant during the study or within 9 days after the end of treatment
210 History of congenital long QT syndrome, second or third degree heart block, ventricular tachyarrythmias, or other conditions associated with prolonged QT interval
At Day 1 Study Visit-All Subjects:
211 Subject has an ongoing adverse event from Studies 20130356 or 20110100 that is considered related to IP and:
• Is ≥ CTCAE (v 4.0) grade 3, and/or
• Considered clinically significant in the opinion of the investigator
212 Central laboratory values (cCa, iPTH) were not obtained/are not available for
• 20130356 week 19 or
• 20140159 Screening visit for subjects from 20110100 study
213 Corrected QT Interval (QTc) > 500 ms, using Bazett’s formula
214 QTc ≥ 450 to ≤ 500 ms, using Bazett’s formula, unless written permission toenroll is provided by the investigator after consultation with a paediatric cardiologist
215 Use of grapefruit juice, herbal medications, CYP3A4 inhibitors (eg, erythromycin, clarithromycin, ketoconazole, itraconazole), or CYP2D6 substrates (eg, flecainide, propafenone, metoprolol, desipramine, nortriptyline, clomipramine)
216 Use of concomitant medications that may prolong the QTc interval
(eg, ondansetron, albuterol)
At Day 1 Study Visit-Subjects Rolling Over from 20130356 Cinacalcet Arm or from 20110100 Study
217 Cinacalcet dose withheld for ≥ last 4 weeks of treatment in studies 20130356 and 201101100. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is subject incidence of events of interest (EOI; hypocalcemia, convulsions, hypotension, worsening of heart failure, hypersensitivity, ischemic heart disease, QT prolongation/ventricular tachyarrhytmias, fracture, acute pancreatitis, drug-related hepatic disorders, nervous system disorders [excluding seizures], neoplastic events, and infection). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The primary analysis will be based on FAS for all secondary endpoints. Summary statistics will be provided for percent change in PTH, iPTH, from baseline to week 3, week 7, week 11, week 15, week 19, week 23, and week 28 within the study population and each age group by previous treatment group in the parent study and overall. No missing data imputation will be used. Summary statistics will be provided for serum cCa and phosphorus values from baseline to week 3, week 7, week 11, week 15, week 19, week 23, and week 28 within the study population and each age group by previous treatment group in the parent study and overall. No imputation of missing data will be utilized.
Additional summary statistics to include iPTH, cCa, and P values from the baseline of the parent study over time to end of this study will also be provided for subjects who are treated with cinacalcet in both studies
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At various timepoints throught the study. |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
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 |
Belgium |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Italy |
Lithuania |
Mexico |
New Zealand |
Poland |
Portugal |
Russian Federation |
Slovakia |
Spain |
Ukraine |
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
|
End of Study per protocol is defined as when the last subject is assessed or receives an intervention for the purposes of final collection of data. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |