E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
with Stage V Chronic Kidney Disease with hyperphosphataemia. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038444 |
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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 long-term safety and tolerability of MCI-196 in subjects with stage V chronic kidney disease on dialysis, with hyperphosphataemia. |
|
E.2.2 | Secondary objectives of the trial |
To assess the long-term efficacy of flexible-dose MCI-196.
To assess the long term safety and efficacy of MCI-196 and sevelamer. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Main Criteria for Inclusion
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, 18 to 80 years of age.
3. The subject has a diagnosis of CKD (Stage V) as defined by the K/DOQI Guidelines (i.e. GFR <15 mL/min/1.73m2 or 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 is undergoing regular dialysis treatment:
o If the subject is on haemodialysis, this is scheduled to occur 3 times per week in a hospital or centre setting. The duration must be between 3 to 5 hours, or if high-flux dialysis is being utilised a minimum of 2.5 hours, depending on the standard of care in each centre.
o If the subject is on peritoneal dialysis, this is scheduled to occur either daily APD (Automated Peritoneal Dialysis) or CAPD (Continuous Ambulatory Peritoneal Dialysis), the latter employing at least 3 bag changes per day.
6. 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.
7. The subject is on a stabilised phosphorus diet, as considered appropriate by the physician.
8. The subject has 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 at enrollment.
9. 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. Specifically, to participate in this study, sexually active females must be 2 or more years post-menopausal, surgically sterilized, or using an accepted form of contraception (oral contraceptives for at least 3 months or an intrauterine device for at least 2 months prior to the start of the screening visit or various barrier methods, e.g., diaphragm or combination condom and spermicide).
10. Male subjects must agree to use appropriate contraception during the course of the clinical study.
11. If the Subject was previously in Study E07 and initially received sevelamer , the subject has completed all 12 weeks of study treatment.
12. If the Subject was previously in Study E07 and initially received MCI-196 or placebo, thesubject has completed all 16 weeks of study treatment.
13. If the Subject was previously in Study E08, the subject has completed all 12 weeks of study treatment.
14. If the Subject was previously in Study E09, the subject has completed all 12 weeks of study treatment. |
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E.4 | Principal exclusion criteria |
Main Criteria for Exclusion
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 PTH level >1000 pg/dL.
4. The subject has a body mass index (BMI) 16.0 kg/m2 or >40.0 kg/m2.
5. The subject has current or 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., hepatitis, 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) at enrolment.
7. The subject is known to have a positive test for hepatitis B surface antigen, hepatitis C antibody or HIV 1 and 2 antibodies.
8. The subject has a history of substance or alcohol abuse within the last year.
9. The subject has seizure disorders.
10. The subject has a history of drug or other allergy that contraindicates their participation.
11. The subject is using any of the following drugs:
o Colesevelam, colestyramine or colestipol
12. The subject has a temporary catheter as a vascular access.
13. The subject has participated in a clinical study with any experimental medication (with the exception of studies MCI-196 E07, E08 or E09) in the last 30 days or an experimental biological product within the last 90 days prior to signing of informed consent.
14. 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 safety variables are the changes from baseline (i.e the start of the previous study) to endpoint in safety parameters (e.g. vital signs, and laboratory values).
モEndpointヤ for Study E10 is defined as week 40 or モlast observationヤ if subject from any study withdraws early
In this way, it is planned that most subjects entering Study E10 and receiving MCI-196 or sevelamer will have the possibility of being exposed to MCI-196 or sevelamer for 52 weeks in total. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | 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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | 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.8.5 | 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 |
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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
| |
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 | 8 |
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 | 8 |