| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Secondary Hyperparathyroidism in Chronic Kidney Disease subjects not receiving dialysis | |
| MedDRA Classification |
| 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 efficacy of cinacalcet compared with placebo by determining the proportion of subjects achieving a mean reduction of ≥ 30% in intact parathyroid hormone (iPTH) during the efficacy assessment phase. | |
| E.2.2 | Secondary objectives of the trial | To evaluate the efficacy of cinacalcet compared with placebo during the efficacy assessment phase by determining:
- The proportion of subjects achieving a target iPTH during the efficacy assessment phase, defined as:
a mean iPTH ≤ 70pg/mL for subjects with stage 3 chronic kidney disease (CKD), or
a mean iPTH ≤ 110pg/mL for subjects with stage 4 CKD
- The mean percent change from baseline in iPTH
To assess the safety and tolerability of cinacalcet compared with placebo in CKD subjects not receiving dialysis by determining:
- The nature, frequency, severity, and relationship to treatment of all adverse events
- Changes in laboratory parameters, including clinical chemistry, hematology, and urine electrolyte excretion (calcium and phosphorus) using 24-hour urine collections.
| |
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria | Males or females ≥ 18 years of age at the start of screening.
Agree to use, in the opinion of the principal investigator, highly effective contraceptive measures throughout the study (all females must have a negative serum pregnancy test within 30 days before day 1).
One iPTH determination obtained from the central laboratory ≥ 100 pg/mL [10.6 pmol/L] for stage 3 CKD or ≥ 160pg/mL [17.0pmol/L] for stage 4 CKD.
One serum calcium determination obtained from the central laboratory ≥ 9.0mg/dL [2.25mmol/L].
CKD subjects not receiving dialysis with an estimated GFR ≤ 59mL/min and ≥ 15mL/min.
Before any study-specific procedure, the appropriate written informed consent must be obtained
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| E.4 | Principal exclusion criteria | Have an unstable medical condition, defined as having been hospitalized within 30 days before day 1, or otherwise unstable in the judgment of the investigator.
Experienced a myocardial infarction (MI) within 3 months before day 1.
Likely to initiate dialysis (in the opinion of the investigator) or are scheduled to undergo renal transplantation within 28 weeks after day 1.
Laboratory evidence of primary HPT.
Received active vitamin D therapy (ie, 1-hydroxylated metabolites of vitamin D) for less than 30 days before day 1 or required a change in active vitamin D brand or dose level within 30 days before day 1 (for subjects prescribed active vitamin D).
Received, within 30 days before day 1, therapy with cinacalcet.
General:
- Other investigational products or procedures.
- 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).
- Pregnant or nursing
- Received a kidney transplant
- Known sensitivity to any of the products to be administered during dosing.
- Gastrointestinal disorder that may be associated with impaired absorption of orally administered medications or has an inability to swallow tablets
- Previous participation in a study with cinacalcet.
- Any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
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| E.5 End points |
| E.5.1 | Primary end point(s) | | The primary endpoint is the proportion of subjects with a mean reduction of ≥ 30% in iPTH during the efficacy assessment phase. For each subject, baseline iPTH is defined as the average of the 2 iPTH values collected during the screening phase and pre-dose on day 1. A responder is defined as a subject whose mean percent reduction from baseline in iPTH during the efficacy assessment phase is ≥ 30%. The mean percent change in iPTH during the efficacy assessment phase is defined as the average percent change of all the available iPTH values at weeks 20, 24, 28, and 32 of the study. For subjects with no data during weeks 20, 24, 28, and 32, the last available post-baseline iPTH value will be used to calculate the endpoint. | |
| 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 | Information not present in EudraCT |
| 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.8.3 | 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 | |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 visit of last subject | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 2 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 2 |
