Hyperphosphataemia MedDRA version: 8.1 Level: LLT Classification code 10020711 Term: Hyperphosphataemia
Conditions
Interventions
Trade Name: CHOLEBINE®
Product Code: MCI-196
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: colestilan
CAS Number: 95522-45-5
Current Sponsor code: MCI-196
Concentration unit: mg milligr
Sponsors
Mitsubishi Tanabe Pharma Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
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, 18 to 80 years of age. 3. The subject has a diagnosis of CKD (Stage V) as defined by the K/DOQI Guidelines 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 binders for at least 3 months. For subjects on calcium based phosphate-binding medication only, current treatment must contain a dose of =1.0 g/day of elemental calcium (i.e equivalent to =2.5 g/day of calcium carbonate or =4g/day of calcium acetate). For subjects on calcium based phosphate-binding medication in combination with non calcium based phosphate-binding medication, current treatment must contain a dose of =0.5 g/day of elemental calcium (i.e equivalent to =1.25 g/day of calcium carbonate or =2 g/day of calcium acetate). 6. The subject is undergoing regular dialysis treatment: - 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 a minimum of 2.5 hours, depending on the standard of care in each centre. - If the subject is on peritoneal dialysis, this is scheduled to be either daily APD (Automated Peritoneal Dialysis) or CAPD (Continuous Ambulatory Peritoneal Dialysis), the latter employing at least 3 bag changes per day. 7. The subject has serum phosphorus levels less than 2.26 mmol/L (7.0 mg/dL) at screening. 8. 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. 9. The subject is on a stabilised phosphorus diet, as considered appropriate by the physician. 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. 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, such as, diaphragm or combination condom and spermicide). 12. Male subjects must agree to use appropriate contraception during the course of the clinical study. Additional Criteria for Randomisation 13. The subject has serum phosphorus level of greater than or equal to 1.94 mmol/L (6.0 mg/dL), and at least 15% greater than at screening after completion of the run-in period. or The serum phosphorus level reaches 2.58 mmol/L (8.0 mg/dL) or greater at any time during the run-in period. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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 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., 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 hepatitis B surface antigen, or HIV 1 and 2 antibodies. The subject is known to have a positive test for hepatitis C antibody. Note: Subjects testing positive for Hep C antibody may be included into the study if, in the investigators opinion, there is no evidence of active disease present as confirmed by PCR. If PCR is not commonly used in that centre, then confirmed by transaminase levels of <3 times the upper limit of normal. 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 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the additive effect of MCI-196 in the control of hyperphosphataemia (in CKD stage V patients on dialysis) when combined with a fixed low dose of a calcium-based phosphate binder. Thus all patients will be treated with a fixed low dose of a calcium-based phosphate binder and in addition will be randomised to receive either MCI-196 or placebo.;Secondary Objective: - To demonstrate superiority of MCI-196 over placebo in the control of other efficacy parameters (such as 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. ;Primary end point(s): The primary endpoint is the change from baseline in serum phosphorus. The primary efficacy analyses will evaluate the change in serum phosphorus (value from central laboratory) from baseline (week 0) to week 12 (or last observation) for low dose calcium plus MCI-196 compared to low dose calcium plus placebo. | — |
Countries
Austria, Czech Republic, France, Germany, Italy, Spain, United Kingdom
Outcome results
None listed