E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary hyperparathyroidism (HPT) in subjects with CKD receiving dialysis |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020708 |
E.1.2 | Term | Hyperparathyroidism secondary |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014646 |
E.1.2 | Term | End stage renal disease (ESRD) |
|
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 describe histomorphometric parameters of bone turnover in dialysis subjects with high turnover renal osteodystrophy during treatment with Sensipar®/Mimpara® with or without concomitant vitamin D sterols and/or phosphate binders therapy. |
|
E.2.2 | Secondary objectives of the trial |
The effects of Sensipar®/Mimpara® on intact parathyroid hormone (iPTH), intact parathyroid hormone (iPTH), bone-specific alkaline phosphatase (BALP), osteocalcin (OC), serum N-telopeptide (NTx), deoxypyridinoline (DPD), and tartrate resistant acid phosphatase (TRAP). The effects of Sensipar®/Mimpara® on serum calcium, serum phosphorus, and Ca x P concentrations. The safety and tolerability of Sensipar®/Mimpara® including its effect on mineralization lag time, osteoid area/volume, osteoid width/thickness, and the incidence of dynamic bone disease. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects will be eligible for the study if they meet all of the following criteria:
Men or women ≥ 18 years of age at screening. Agree to use, in the opinion of the principal investigator, highly effective contraceptive measures throughout the study. One iPTH determination obtained from the central laboratory must be ≥ 300 pg/mL (31.8 pmol/L). One serum calcium determination obtained from the central laboratory must be ≥8.4 mg/dL (2.1 mmol/L). One BALP determination obtained from the central laboratory must be > 20.9 ng/mL. Positive histologic confirmation of high bone turnover disease. Positive confirmation is defined as any of the following: • Osteoid area < 12%, BFR > 613 µm2/mm2/day, and no evidence of fibrosis • Osteoid area < 12%, BFR > 97 µm2/mm2/day, and evidence of fibrosis • Osteoid area > 12%, BFR > 97 µm2/mm2/day, with or without evidence of fibrosis Treated with dialysis for ≥ 1 month before the date of informed consent. Ethical - Before any study-specific procedure, the appropriate written informed consent must be obtained |
|
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. Are pregnant or nursing women. Had a parathyroidectomy in the 3 months before the date of informed consent. For subjects prescribed vitamin D, have received vitamin D therapy for less than 30 days before day 1 or required a change in vitamin D brand or dose level within 30 days before day 1. Received within 30 days before day 1, therapy FORTEO. Ever received therapy with Sensipar®/Mimpara® Ever received therapy with bisphosphonates 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Primary
Change from baseline in BFR
Secondary
• Change from baseline in osteoblasts perimeter and osteoclasts perimeter • Change from baseline in eroded perimeterand evidence of fibrosis area • Percent change from baseline in iPTH, iPTH, BALP, OC, serum NTx, DPD, and TRAP • Percent change from baseline in serum calcium, serum phosphorus, and Ca x P
Safety
Change from baseline in mineralization lag time, osteoid area/volume, and osteoid width/thickness • The occurrence of adynamic bone disease as defined by: • Osteoid area < 12%, AND • BFR < 97 µm2/mm2/day, AND • no evidence of fibrosis • Nature, frequency, severity, and relationship to treatment of adverse events; and changes in laboratory parameters. |
|
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) | 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 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 | 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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |