Chronic Kidney Disease, Dialysis, Hyperphosphatemia
Conditions
Keywords
Chronic Kidney Disease, Dialysis, Hyperphosphatemia, Phosphate binder
Brief summary
This is a phase III multi-centre study in three periods: the first period is a phosphate binder washout for 4 weeks, the second period is an open-label, flexible dose titration, the third period is a placebo-controlled withdrawal comparing MCI-196 with placebo for 4 weeks.
Interventions
DRUGMCI-196
3g to 15g/day (3 times a day), Tablet, 12 weeks of flexible dose (Open-label) and 4 weeks of double blind
DRUGPlacebo
3g to 15g/day (3 times a day), Tablet, 4 weeks of double blind
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, and is \>=18 years old * Stable hemodialysis or peritoneal dialysis * Subjects has Stable phosphate control * Subjects on Stabilized phosphorus diet * Subjects undergoing regular dialysis treatment * 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 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. * serum albumin level \< 3.0g/dL * PTH level \> 1000pg/mL * Hemoglobin level \< 8mg/dL * A History of significant gastrointestinal motility problems * Biliary obstruction or proven liver dysfunction * A positive test for hepatitis B surface antigen, hepatitis C antibody or HIV 1 and 2 antibodies * A clinically significant severe lactose intolerance or sensitivity * A history of substance or alcohol abuse within the last year. * Seizure disorders * A history of drug or other allergy * using cholestyramine, colestipol or colesevelam * Schedule to receive a kidney transplant within the next 6 months * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Serum Phosphorus From Week 12 to Week 16 | 4 weeks (Week 12 to Week 16) | The changes in serum phosphorus (mg/dL) from Week 12 to Week 16 (last observation post Week 12) |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Serum Phosphorus | 12 weeks (Week 0 to Week 12) |
| Change From Baseline in PTH | 12 weeks |
| Change From Baseline in Calcium | 12 weeks |
| Change From Baseline in Calcium x Phosphorus Ion Product | 12 weeks |
| Change From Baseline in Total Cholesterol | 12 weeks |
| Change From Baseline in LDL Cholesterol | 12 weeks |
| Change From Baseline in HDL Cholesterol | 12 weeks |
| Change From Baseline in VLDL Cholesterol | 12 weeks |
| Change From Baseline in Triglyceride | 12 weeks |
| Incidence of Adverse Events | 12 weeks (Week 0-12) and 4 weeks (Week 12-16) |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-196 Open-label Period (Week 0 - 12) ; 3, 6, 9, 12, or 15 g/ day as titrated
Double-blind Period (Week 12 - 16) ; dose level at the end of dose titration in the Open-label period | 245 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1; Open-label Period | Adverse Event | 21 | 0 |
| Period 1; Open-label Period | Lack of Efficacy | 13 | 0 |
| Period 1; Open-label Period | Lost to Follow-up | 2 | 0 |
| Period 1; Open-label Period | Other Reasons | 13 | 0 |
| Period 1; Open-label Period | Physician Decision | 5 | 0 |
| Period 1; Open-label Period | Protocol Violation | 9 | 0 |
| Period 1; Open-label Period | Withdrawal by Subject | 13 | 0 |
| Period 2; Double-blind Period | Adverse Event | 0 | 1 |
| Period 2; Double-blind Period | Lack of Efficacy | 0 | 2 |
| Period 2; Double-blind Period | Other Reason | 1 | 1 |
| Period 2; Double-blind Period | Physician Decision | 1 | 1 |
| Period 2; Double-blind Period | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | MCI-196 |
|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 12.9 |
| Sex: Female, Male Female | 99 Participants |
| Sex: Female, Male Male | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 161 / 245 | 34 / 86 | 25 / 83 |
| serious Total, serious adverse events | 37 / 245 | 10 / 86 | 7 / 83 |
Outcome results
Primary
The Change in Serum Phosphorus From Week 12 to Week 16
The changes in serum phosphorus (mg/dL) from Week 12 to Week 16 (last observation post Week 12)
Time frame: 4 weeks (Week 12 to Week 16)
Population: Intent-to-treat (ITT) 2 (The ITT2 population included all subjects who complete 12-weeks, receive a randomization number and receive at least one dose of study medication in the placebo-controlled withdrawal phase, either MCI-196 or placebo, and have at least one central phosphorus value after 12-weeks.)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196 (Double-blind Period) | The Change in Serum Phosphorus From Week 12 to Week 16 | -0.04 mg / dL | Standard Deviation 1.49 |
| Placebo (Double-blind Period) | The Change in Serum Phosphorus From Week 12 to Week 16 | 0.71 mg / dL | Standard Deviation 1.71 |
Secondary
Change From Baseline in Calcium
Time frame: 12 weeks
Secondary
Change From Baseline in Calcium x Phosphorus Ion Product
Time frame: 12 weeks
Secondary
Change From Baseline in HDL Cholesterol
Time frame: 12 weeks
Secondary
Change From Baseline in LDL Cholesterol
Time frame: 12 weeks
Secondary
Change From Baseline in PTH
Time frame: 12 weeks
Secondary
Change From Baseline in Serum Phosphorus
Time frame: 12 weeks (Week 0 to Week 12)
Population: ITT1 (The ITT1 population included all enrolled subjects who have taken at least one dose of study medication and have at least one central phosphorus value after the start of study medication.)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MCI-196 (Double-blind Period) | Change From Baseline in Serum Phosphorus | -1.54 mg/dL |
Secondary
Change From Baseline in Total Cholesterol
Time frame: 12 weeks
Secondary
Change From Baseline in Triglyceride
Time frame: 12 weeks
Secondary
Change From Baseline in VLDL Cholesterol
Time frame: 12 weeks
Secondary
Incidence of Adverse Events
Time frame: 12 weeks (Week 0-12) and 4 weeks (Week 12-16)