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

• ClinicalTrials.gov Identifier: NCT00858637
• Recruitment Status: Completed
• First Posted: March 10, 2009
• Results First Posted: October 17, 2014
• Last Update Posted: December 30, 2014
• Sponsor: Mitsubishi Tanabe Pharma Corporation
• Information provided by (Responsible Party): Mitsubishi Tanabe Pharma Corporation

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease	Drug: MCI-196; Drug: Placebo of Simvastatin; Drug: Simvastatin; Drug: Placebo of MCI-196	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 260 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: March 2009
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: March 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1 MCI-196	Drug: MCI-196; 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); Other Names: Colestilan(INN); Colestimide(JAN); CHOLEBINE®; BindRen®; Drug: Placebo of Simvastatin; 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)
Placebo Comparator: 2 Placebo of MCI-196	Drug: Placebo of Simvastatin; 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); Drug: Placebo of MCI-196; 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)
Active Comparator: 3 Simvastatin	Drug: Simvastatin; 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); Drug: Placebo of MCI-196; 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)
Placebo Comparator: 4 Placebo of Simvastatin	Drug: Placebo of Simvastatin; 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); Drug: Placebo of MCI-196; 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)

Outcome Measures

Primary Outcome Measures :

1. Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2) [ Time Frame: week20 minus week16 ]
   Percent Change from Week 16 to Week 20 (LOCF)

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Belarus

Brest, Belarus

Gomel, Belarus

Grodno, Belarus

Minsk, Belarus

Vitebsk, Belarus

Bulgaria

Gabrovo, Bulgaria

Plovdiv, Bulgaria

Sofia, Bulgaria

Croatia

Karlovac, Croatia

Osijek, Croatia

Denmark

Esbjerg, Denmark

Roskilde, Denmark

Indonesia

Jakarta, Indonesia

Malang, Indonesia

Medan, Indonesia

Palembang, Indonesia

Tamanlarea Makassar, Indonesia

Israel

Ashkelon, Israel

Nahariya, Israel

Italy

Bellano, Italy

Catania, Italy

Lecco, Italy

Merate, Italy

Milano, Italy

Oggiono, Italy

Latvia

Riga, Latvia

Valmiera, Latvia

Lithuania

Kaunas, Lithuania

Kedauniai, Lithuania

Vilnius, Lithuania

Malaysia

Johor, Malaysia

Kelantan, Malaysia

Penang, Malaysia

Perak, Malaysia

Romania

Bucharest, Romania

Timisoara, Romania

Singapore

Singapore, Singapore

Thailand

Bangkok, Thailand

Phitsanulok, Thailand

Sponsors and Collaborators

Mitsubishi Tanabe Pharma Corporation

Investigators

• Principal Investigator: Professor; Information at Mitsubishi Pharma Europe

More Information

• Responsible Party: Mitsubishi Tanabe Pharma Corporation
• ClinicalTrials.gov Identifier: NCT00858637
• Other Study ID Numbers: MCI-196-E11
• First Posted: March 10, 2009
• Results First Posted: October 17, 2014
• Last Update Posted: December 30, 2014
• Last Verified: December 2014

Keywords provided by Mitsubishi Tanabe Pharma Corporation:

Chronic Kidney Disease; Dialysis; Dyslipidemia; Bile acid sequestrant

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Dyslipidemias; Urologic Diseases; Renal Insufficiency; Lipid Metabolism Disorders; Metabolic Diseases; Bile Acids and Salts; Simvastatin; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Gastrointestinal Agents