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. |
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E.1.1.1 | Medical condition in easily understood language |
Secondary Hyperparathyroidism
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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 | 14.0 |
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 |
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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 determine the efficacy of a secondary HPT treatment regimen including cinacalcet compared to a treatment regimen not including cinacalcet (placebo) on the composite of time to all-cause mortality or first non-fatal cardiovascular event (myocardial infarction [MI], hospitalization for unstable angina, heart failure [HF], or peripheral vascular event). |
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E.2.2 | Secondary objectives of the trial |
To assess the effects of a secondary HPT treatment regimen including cinacalcet versus a treatment regimen not including cinacalcet, by determining:
• All-cause mortality
• Cardiovascular mortality
• Fatal and non-fatal MI
• Fatal and non-fatal hospitalization for unstable angina
• Fatal and non-fatal HF event
• Fatal and non-fatal peripheral vascular event
• Fatal and non-fatal stroke
• Bone fracture
• Parathyroidectomy
• The safety and tolerability of cinacalcet. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Men or women ≥ 18 years of age at screening.
Treated with maintenance hemodialysis 3 times a week for ≥ 3 months before randomization.
PTH obtained from the central laboratory must be ≥ 300 pg/mL (31.8 pmol/L).
Serum calcium obtained from the central laboratory must be ≥ 8.4 mg/dL (2.1 mmol/L).
Ca x P obtained from the central laboratory must be ≥ 45 mg2/dL2 (3.63 mmol2/L2).
In the investigator’s opinion, the subject is likely to be available during the follow up phase of the study.
Agree to be followed for study endpoints until the end of study.
Ethical - Before any study-specific procedure, the appropriate written informed consent must be obtained (see Section 13.1). |
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E.4 | Principal exclusion criteria |
Subjects will be ineligible for the study if they:
Have an unstable medical condition in the judgment of the investigator.
Parathyroidectomy in the 12 weeks before the date of informed consent.
Severe (ie, life-limiting) concomitant disease, including life-threatening malignancy or acquired immune deficiency syndrome (if likely to reduce life expectancy to less than 5 years), or any other life-threatening concomitant disease. Subjects with excised superficial lesions (eg, basal cell and squamous cell carcinoma of the skin) may be included.
Received therapy with cinacalcet within 3 months of randomization.
Hospitalization within 12 weeks of randomization for any of the following events:
a. Myocardial infarction
b. Unstable angina
c. Heart failure (including any unplanned presentation to a health care facility that would require mechanical intervention [ie, unplanned dialysis treatment])
d. Peripheral vascular disease (other than for dialysis vascular access revision)
e. Stroke
History of seizure within 12 weeks prior to randomization.
Scheduled date for kidney transplant from a known living donor.
Anticipated parathyroidectomy within 6 months after randomization.
General:
- Other investigational procedures are excluded.
- Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s).
- Subject has known sensitivity or intolerance to any of the products to be administered for the purpose of this study.
- Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
- Subject is pregnant, is breast feeding, or is of child-bearing potential and not using adequate contraceptive precautions. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to the composite event comprising all-cause mortality or non-fatal cardiovascular events (MI, hospitalization for unstable angina, HF, or peripheral vascular event). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Time to all-cause mortality
Time to cardiovascular mortality
Time to fatal and non-fatal MI
Time to fatal and non-fatal hospitalization for unstable angina
Time to fatal and non-fatal HF event
Time to fatal and non-fatal peripheral vascular event
Time to fatal and non-fatal stroke
Time to bone fracture
Time to parathyroidectomy |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For all secondary endpoints: At the end of the study |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 205 |
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 |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Denmark |
France |
Germany |
Hungary |
Ireland |
Italy |
Mexico |
Netherlands |
Poland |
Portugal |
Puerto Rico |
Russian Federation |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |