E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10020712 |
E.1.2 | Term | Hyperphosphatemia |
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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 |
This is a 2-stage re-randomization design where Stage 1 is a randomized, open label comparison between fermagate and lanthanum carbonate (in a non-inferiority design) and Stage 2 is a randomized double blind comparison between fermagate and placebo (in a superiority design).
Stage 1: Primary Objective: The primary objective is to establish the efficacy of fermagate by demonstrating the non-inferiority (with possible assessment of superiority) of fermagate to lanthanum carbonate in lowering serum phosphate in hemodialysis patients.
Objectives at Stage 2 Stage 2 will use patients who complete the 3-month maintenance period of Stage 1 and who were originally randomized to fermagate.
Stage 2 :Primary Objective The primary objective is to establish efficacy of fermagate by demonstrating the superiority of fermagate over placebo in lowering serum phosphate in hemodialysis patients
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E.2.2 | Secondary objectives of the trial |
Stage 1: Secondary objectives: The secondary objectives are to: • Determine the safety of fermagate in hemodialysis patients • Compare the effects of fermagate and lanthanum carbonate on measures of mineral metabolism, albumin, pre-albumin and iron status
Stage 2: Secondary objectives: The secondary objectives are to: • Determine the safety of fermagate in hemodialysis patients • Compare the effects of fermagate and placebo on measures of mineral metabolism, albumin, pre-albumin and iron status
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, aged 18 years or older. 2. Able to comply with the study procedures and medication. 3. Written informed consent given. 4. On a stable hemodialysis regimen (at least 3x per week) for at least 12 weeks prior to screening. 5. (a) Subject receiving phosphate binder medication(s) at screening, must have been on a stable regimen (dose and medication) for at least 1 month prior to screening and will remain on this regimen until entry into the washout period OR 5. (b) Subjects (i) is not currently receiving any phosphate binding medication at screening (or medication likely to act as a phosphate binder) and (ii) must not have done so for at least one month and (iii) has sustained hyperphosphatemia. 6. Willing to abstain from taking any phosphate binder or oral magnesium-, oral aluminum- or oral iron-containing products and preparations other than the study medication. 7. If required to take >6000 mg/day of fermagate, the subject will be willing to have at least three meals per day.
Specifically, for randomization and inclusion into the treatment period, the following criterion must be fulfilled:
8. Has a serum phosphate value of ≥1.94 mmol/L (≥6.0 mg/dL) within the 2 to 4 week washout period or above 3.0 mmol/L (9.3 mg/dL) at any time during washout.
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E.4 | Principal exclusion criteria |
1. Participation in any clinical trial using an investigational product or device during the 30 days preceding the Screening Visit. 2. Previous experience of fermagate treatment. 3. A significant history of alcohol, drug or solvent abuse in the opinion of the investigator. 4. Any disease or condition, physical or psychological that, in the opinion of the investigator, would compromise the safety of the subject or the likelihood of achieving reliable results or increase the likelihood of the subject being withdrawn. 5. Laboratory findings at screening which, in the opinion of the investigator, are clinically significant for this subject population. 6. A screen serum magnesium concentration of >3.0 mg/dL (>1.25 mmol/L). 7. A known history of hemochromatosis. 8. Subjects receiving either tetracycline or lithium treatment. 9. A serum ferritin level of ≥1000 ng/mL. 10. Non-elective hospitalization in the 4 weeks prior to screening. 11. Female subjects who are of childbearing potential and who are neither surgically sterilized nor using reliable contraceptive methods (hormonal, barrier methods or intrauterine device) or who are lactating or pregnant. 12. Current hypophosphatemia at screening (last 2 consecutive phosphate values of <2.2 mg/dL [<0.7 mmol/L]). 13. Known history of colorectal malignancy, familial polyposis coli and/or strong family history (in 2 or more first degree relatives) of these terms. 14. A QTcF interval of >560 ms at screen. 15. Known persistent (>1 month) non compliance (<70%) with prescribed medication regimens at screen. 16. Current clinically significant intestinal motility disorder. 17. Intestinal motility disorder with current or previous use of lanthanum carbonate. 18. Known intolerance to lanthanum carbonate or any excipients of fermagate or Fosrenol medication. 19. Subjects with inflammatory bowel disease that, in the investigator’s opinion, is poorly controlled.
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E.5 End points |
E.5.1 | Primary end point(s) |
(Stage 1) Primary efficacy endpoint: Control of serum phosphate defined as (1) a mean serum phosphate of 2.5 to 5.5 mg/dL (0.8 to 1.78 mmol/L) and (2) a difference from baseline in the serum phosphate concentrations used for the mean, of at least 0.93 mg/dL (0.3 mmol/L). The mean serum phosphate concentration will be calculated using the last two serum phosphate concentrations in the Treatment Period; if only one serum phosphate concentration is available this will be taken as the mean; if a subject has withdrawn from the Treatment Period due to abnormal serum phosphate concentrations then he/she will be deemed a non-responder (uncontrolled), regardless of their calculated mean serum phosphate concentration.
The primary efficacy analysis will use the ITT and PP populations
(Stage 2) Primary efficacy endpoint: Change from treated baseline in mean serum phosphate at 4 weeks (treated baseline is mean serum phosphate at the end of the maintenance period).
The primary efficacy analysis will use the ITT population
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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 | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
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) | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
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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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The end of the trial is defined as 30 days after the last subject received study medication (i.e. the end of the SAE reporting period). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 9 |