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 | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10020711 |
E.1.2 | Term | Hyperphosphataemia |
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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 demonstrate the superiority of MCI-196 over placebo in the control of serum phosphorus in subjects with Stage V Chronic Kidney Disease on dialysis. |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate superiority of MCI-196 over placebo in the control of other efficacy parameters (e.g. LDL-cholesterol, other lipid parameters, PTH, calcium, Ca x P ion product) in subjects with Stage V Chronic Kidney Disease on dialysis. - To assess the safety and tolerability of flexible-dose MCI-196 compared to sevelamer. - To assess the efficacy of flexible-dose MCI-196 compared to sevelamer. - To assess the mean daily dose of MCI-196 compared to sevelamer.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject is capable of reading and comprehending the informed consent and complying with study procedures and provides written informed consent. 2. The subject is male or female and 18 years of age or over. 3. The subject has a diagnosis of CKD (Stage V) as defined by the K/DOQI Guidelines and is on dialysis. 4. The subject is clinically stable on haemodialysis or peritoneal dialysis for at least 3 months, as judged by the Investigator. 5. The subject has stable phosphate control (as judged by the investigator) using phosphate-binding medication for at least 1 month prior to the screening visit. 6. The subject is on a stabilised phosphorus diet, as considered appropriate by the physician. 7. The subject is undergoing regular dialysis treatment: - If the subject is on haemodialysis, this is scheduled 3 times per week in a hospital or centre setting. The duration must be between 3 to 5 hours or if high-flux dialysis a minimum of 2.5 hours, depending on the standard of care in each centre. - If the subject is on peritoneal dialysis, this is either daily APD (Automated Peritoneal Dialysis) or CAPD (Continuous Ambulatory Peritoneal Dialysis), the latter employing at least 3 bag changes per day. 8. The subject has serum phosphorus level, as measured by the Central Laboratory, less than 2.42 mmol/L (7.5 mg/dL) at screening. 9. The subject has calcium dialysate content between 1 to 1.75 mmol/L (2 to 3.5 mEq/L), depending on the standard of care in each centre. Calcium dialysate content should remain constant for the duration of the study. 10. The subject has baseline Kt/V (single pool) of at least 1.2 for haemodialysis subjects, and a weekly Kt/V value of at least 1.8 for peritoneal dialysis subjects. 11. The subject, if female and of child-bearing potential, has a negative serum pregnancy test. Sexually active females must agree to take appropriate steps not to become pregnant during the course of the clinical study. 12. Male subjects must agree to use appropriate contraception during the course of the clinical study.
Additional Criteria for Randomisation at Visit 5 (Baseline Visit):
13. At Visit 3 (Week -2) or Visit 4 (Week -1), the subject has a serum phosphorus level, as measured by the Central Laboratory, of greater than or equal to 1.94 mmol/L (6.0mg/dL) and is at least 15% greater than at screening or At Visit 2 (Week -3), the subject has a serum phosphorus level, as measured by the Central Laboratory, of greater than or equal to 2.58mmol/L (8.0mg/dL) and is at least 15% greater than at screening.
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E.4 | Principal exclusion criteria |
1. The subject has current clinically significant medical comorbidities, which may substantially compromise subject safety, or expose them to undue risk, or interfere significantly with study procedures and which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study. 2. The subject has a serum albumin level <30.0 g/L. 3. The subject has a history of PTH levels consistently/frequently >1000 pg/mL. 4. The subject has a body mass index (BMI) ≤16.0 kg/m2 or ≥40.0 kg/m2. 5. The subject has currently or has a history of significant gastrointestinal (GI) motility problems, including dysphagia or swallowing difficulty, or GI abnormalities such as chronic or severe constipation, sigmoid colitis, ulcers, or major GI surgery. 6. The subject has biliary obstruction or proven liver dysfunction, i.e. cirrhosis, hepatorenal syndrome, or has liver function tests 3 times the normal values for at least 2 of the measurements (ALT, AST, alkaline phosphatase, and gamma-glutamyl-transferase) . 7. The subject is known to have a positive test for HIV 1 and 2 antibodies. 8. The subject has a history of clinically significant severe lactose intolerance or sensitivity (the placebo tablets have a high lactose content), as judged by the investigator. 9. The subject has a history of substance or alcohol abuse within the last year. 10. The subject has seizure disorders. 11. The subject has a history of drug or other allergy that contraindicates their participation. 12. The subject is using any of the following drugs: - over-the-counter products containing calcium, magnesium and aluminium, and/or nutritional supplements which can not be stopped during the study period - colestyramine, colestipol or colesevelam 13. The subject has a temporary catheter as a vascular access and is showing active signs of inflammation or infection as a result of this. 14. The subject has participated in a clinical study with any experimental medication in the last 30 days or an experimental biological product within the last 90 days, prior to signing of the informed consent. 15. The subject has had prior to exposure to MCI-196 in the past 12 months. 16. If on peritoneal dialysis, the subject has a recent history of peritonitis (within the previous 3 months).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change from Week 12 to Week 16 or last observation in serum phosphorus for MCI-196 and placebo. The primary efficacy analysis will evaluate change in serum phosphorus from Week 12 to the end of Week 16 (or at last observation) for MCI-196 compared to placebo. |
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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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
withdrawal; flexible dose; dose comparison |
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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 | Information not present in EudraCT |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 | 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
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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 | |
E.8.9.1 | In the Member State concerned months | 30 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 30 |