Efficacy and Safety Study of MCI-196 Versus Simvastatin for Dyslipidaemia in Chronic Kidney Disease (CKD) Subjects on Dialysis

Study Overview
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Brief Summary
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The primary objective of this study is to demonstrate the superiority of MCI-196 over placebo and non-inferiority with simvastatin in reducing serum low-density lipoprotein (LDL)-cholesterol in subjects with chronic kidney disease Stage V on dialysis. This study incorporates a Washout Period and two treatment periods - an active comparison phase and a placebo-controlled withdrawal phase.

Official Title
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A Phase III, Multicentre, Double-blind, Double-dummy, Randomised, Flexible-dose, Comparative Study of MCI-196 Versus Simvastatin for the Treatment of Dyslipidaemia in Subjects With Chronic Kidney Disease on Dialysis (Incorporating a Placebo-controlled Withdrawal Phase)

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: MCI-196
* Drug: Placebo of Simvastatin
* Drug: Simvastatin
* Drug: Placebo of MCI-196


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, and is >=18 years old Stable hemodialysis or peritoneal dialysis Subjects undergoing regular dialysis treatment If Female and of child-bearing potential, have a negative serum pregnancy test Male subjects must agree to use appropriate contraception Exclusion Criteria: 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, makes the subject unsuitable for inclusion in the study Serum albumin level < 30 g/L Triglycerides level > 6.76 mmol/L (600 mg/dL) LDL-cholesterol level > 4.94 mmol/L (190 mg/dL) A History of significant gastrointestinal motility problems Biliary obstruction or proven liver dysfunction A positive test for HIV 1 and 2 antibodies A history of substance or alcohol abuse within the last year The subject has a history of rhabdomyolysis or myopathy Schedule to receive a kidney transplant within the next 6 months The subject has porphyria Participation 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 informed consent

Ages Eligible for Study
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Minimum 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 MCI-196<br> | Drug: MCI-196<br>* Tablets of 3 g to 12 g/day (3 times a day) with dose escalation design during 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)<br>* Other names: BindRen®;Drug: Placebo of Simvastatin<br>* Tablets once a day, for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)<br>|
| Placebo Comparator: 2 Placebo of MCI-196<br> | Drug: Placebo of Simvastatin<br>* Tablets once a day, for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)<br>Drug: Placebo of MCI-196<br>* Tablets 3 times a day for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)<br>|
| Active Comparator: 3 Simvastatin<br> | Drug: Simvastatin<br>* Tablets of 10 mg to 40 mg/day (once a day) with dose escalation design during 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)<br>Drug: Placebo of MCI-196<br>* Tablets 3 times a day for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)<br>|
| Placebo Comparator: 4 Placebo of Simvastatin<br> | Drug: Placebo of Simvastatin<br>* Tablets once a day, for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)<br>Drug: Placebo of MCI-196<br>* Tablets 3 times a day for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2) | Percent Change from Week 16 to Week 20 (LOCF) | week20 minus week16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Serum LDL-cholesterol Levels From Baseline to Week 16 (LOCF) (ITT1) | Percent Change from Baseline to Week 16 (LOCF) | week16 minus week0 | 
| Change in Phosphorus(P), Calcium(Ca), Calcium-phosphorus Ion Product(PxCa) and Parathyroid Hormone (PTH) |  | 16 weeks and 20 weeks | 
| Vital Signs, Adverse Events, and Laboratory Values |  | throughout study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease, Dialysis, Dyslipidemia, Bile acid sequestrant