Dose-finding Study of MCI-196

Study Overview
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Brief Summary
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The Primary Objective of this study is to determine the initial starting doses of colestilan (MCI-196) in paediatric subjects with Chronic Kidney Disease Stage 5 on Dialysis and with Hyperphosphataemia.

Detailed Description
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This study has been terminated because of insufficient patient recruitment. There were no safety concerns.

Official Title
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A Multi-centre, Randomised, Controlled, Parallel Group, Open-label Study Evaluating the Efficacy, Safety and Tolerability of Three Doses of Colestilan (MCI-196) Compared to Standard Therapy With a Calcium-based Phosphate Binder, in Paediatric Subjects With Chronic Kidney Disease Stage 5 on Dialysis and With Hyperphosphataemia

Conditions
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Chronic Kidney Disease, Dialysis, Hyperphosphatemia, Paediatric

Intervention / Treatment
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* Drug: colestilan-L
* Drug: colestilan-M
* Drug: colestilan-H
* Drug: CBPB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 2 years to <18 years with CKD stage 5 on dialysis (haemodialysis or peritoneal dialysis) for at least one month The subject has a documented diagnosis of hyperphosphataemia, as demonstrated by serum phosphorus(P) levels above the age-related upper limit of normal KDOQI Clinical Practice Guidelines for Nutrition in Children with CKD updated 2008) The subject has been taking CBPB prior to enrolment into the study (i.e., prior to the screening visit) The subject must have demonstrated serum P levels >1.5 standard deviation (SD) above the KDOQI 2008 age-related mean value at any time during the wash-out period (this must be demonstrated after stopping treatment with CBPB) At the time of randomisation, the subject must have demonstrated an increase in serum P levels from his/her most recent P central laboratory measurement by at least 10% above the pre-wash-out level Exclusion Criteria: The subject has been diagnosed with hypocholesterolaemia (i.e., cholesterol levels below age-related normal ranges, per local practices) The subject has current clinically significant medical comorbidities, which may substantially compromise subject safety, or expose him/her to undue risk, or interfere significantly with study procedures and which, in the opinion of the Investigator, make the subject unsuitable for inclusion in the study (e.g., the subject currently has or has had a history of seizure disorders, dysphagia, swallowing disorders, predisposition to or current bowel obstruction, ileus or severe gastrointestinal [GI] disorders such as chronic or severe constipation [as judged by the Investigator], intestinal stenosis, intestinal diverticulum, sigmoid colitis, GI ulcers, current or a history of GI bleeding, or major GI tract surgery) The subject was treated with a combination of two or more phosphate binders within one month prior to screening The subject cannot stop treatment (prescription or over-the counter) of any of the following orally taken medications during the wash-out period: any product containing calcium (Ca), magnesium (Mg), aluminium compounds, sevelamer, lanthanum, ketosteril The subject is receiving immunosuppressant treatment for any medical condition at the time of randomisation or is expected to receive such treatment during the course of the study The subject is considered unstable on his/her current treatment for CKD within one month prior to screening (e.g., subjects starting treatment with vitamin D or its analogues, or other agents/procedures that may influence bone mineral metabolism [i.e., serum P and Ca levels])

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MCI-196-L<br>MCI-196 BSA eq 3g | Drug: colestilan-L<br>* body surface area equivalent (BSAeq) 3 g/day<br>* Other names: BindRen;|
| Experimental: MCI-196-M<br>MCI-196 BSA eq 6g | Drug: colestilan-M<br>* BSAeq 6 g/day<br>* Other names: BindRen;|
| Experimental: MCI-196-H<br>MCI-196 BSA eq 9g | Drug: colestilan-H<br>* BSAeq 9 g/day<br>* Other names: BindRen;|
| Active Comparator: CBPB<br>Calcium-based P binder | Drug: CBPB<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean absolute change in serum phosphorus |  | 17 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of responders (responders are defined as subjects demonstrating serum P levels ≤1.5 SD above the KDOQI 2008 age-related mean value) | Kidney Disease Outcomes Quality Initiative(KDOQI) | 17 weeks | 
| Mean absolute change in efficacy laboratory parameters (i.e.,P, Ca, Ca P ion product [CaxP], intact parathyroid hormone [iPTH], serum glucose, glycosylated haemoglobin [HbA1c], and uric acid) |  | 17 weeks | 
| Mean percentage change in other efficacy laboratory parameters (i.e., lipid parameters [low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides (TG)]) |  | 17 weeks |