Chronic Kidney Disease, 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, randomised, parallel group, flexible dose, the third period is a placebo-controlled withdrawal comparing MCI-196 with placebo for 4 weeks.
Interventions
DRUGMCI-196 (Colestilan(INN), Colestimide(JAN), CHOLEBINE®)
3g to 15g/day (3 times a day), Tablet, 12 weeks of flexible dose and 4 weeks of double blind
DRUGPlacebo
3g to 15g/day (3 times a day), Tablet, 4 weeks of double blind
Current approved dosing recommendations for 12 weeks
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, 18 years of age or over * Clinically stable haemodialysis or peritoneal dialysis * Stable phosphate control * On a stabilised phosphorus diet * 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. * Body Mass Index (BMI) \<=16.0 kg/m2 or \>=40.0 kg/m2 * A current or history of significant gastrointestinal motility problems * A positive test for HIV 1 and 2 antibodies * A history of substance or alcohol abuse within the last year. * Seizure disorders * A history of drug or other allergy * A temporary catheter as a vascular access * 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 informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Phosphorus Levels From Week 12 to Week 16 (LOCF) (ITT2) | week16 minus week12 | ITT2 population included all re-randomised subjects who completed 12 weeks in the MCI-196 treatment group and received at least 1 dose of study medication in the placebo-controlled withdrawal period and had at least 1 central serum phosphorus value after 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Phosphorus Levels From Baseline to Week 12 (LOCF) (ITT1) | week12 minus week0 | ITT1 population included all subjects who received a randomisation number (at Week 0), took at least 1 dose of study medication and had at least 1 central serum phosphorus value after the start of study medication. |
Countries
Australia, Austria, Czechia, France, Germany, Hungary, Italy, Poland, South Africa, Spain, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-196 (Open-label Period) | 162 |
| Sevelamer (Open-label Period) | 169 |
| Total | 331 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Open-label Period | Adverse Event | 28 | 10 | 0 | 0 |
| Open-label Period | Death | 2 | 1 | 0 | 0 |
| Open-label Period | Lack of Efficacy | 8 | 1 | 0 | 0 |
| Open-label Period | Other Reasons | 3 | 12 | 0 | 0 |
| Open-label Period | Protocol Violation | 3 | 3 | 0 | 0 |
| Open-label Period | Withdrawal by Subject | 16 | 5 | 0 | 0 |
| Placebo-controlled Withdrawal Period | Adverse Event | 0 | 0 | 0 | 1 |
| Placebo-controlled Withdrawal Period | Lack of Efficacy | 0 | 0 | 0 | 3 |
| Placebo-controlled Withdrawal Period | Protocol Violation | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | MCI-196 (Open-label Period) | Sevelamer (Open-label Period) | Total |
|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 14.7 | 59.5 years STANDARD_DEVIATION 13.8 | 58.0 years STANDARD_DEVIATION 14.3 |
| Sex: Female, Male Female | 54 Participants | 72 Participants | 126 Participants |
| Sex: Female, Male Male | 108 Participants | 97 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 126 / 162 | 113 / 169 | 20 / 50 | 23 / 53 |
| serious Total, serious adverse events | 26 / 162 | 25 / 169 | 2 / 50 | 3 / 53 |
Outcome results
Primary
Change in Serum Phosphorus Levels From Week 12 to Week 16 (LOCF) (ITT2)
ITT2 population included all re-randomised subjects who completed 12 weeks in the MCI-196 treatment group and received at least 1 dose of study medication in the placebo-controlled withdrawal period and had at least 1 central serum phosphorus value after 12 weeks.
Time frame: week16 minus week12
Population: ITT2 population included all re-randomised subjects who completed 12 weeks in the MCI-196 treatment group and received at least 1 dose of study medication in the placebo-controlled withdrawal period and had at least 1 central serum phosphorus value after 12 weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196 (Placebo-controlled Withdrawal Period) | Change in Serum Phosphorus Levels From Week 12 to Week 16 (LOCF) (ITT2) | -0.24 mg / dL | Standard Deviation 1.46 |
| Placebo (Placebo-controlled Withdrawal Period) | Change in Serum Phosphorus Levels From Week 12 to Week 16 (LOCF) (ITT2) | 1.27 mg / dL | Standard Deviation 1.48 |
Secondary
Change in Serum Phosphorus Levels From Baseline to Week 12 (LOCF) (ITT1)
ITT1 population included all subjects who received a randomisation number (at Week 0), took at least 1 dose of study medication and had at least 1 central serum phosphorus value after the start of study medication.
Time frame: week12 minus week0
Population: ITT1 population included all subjects who received a randomisation number (at Week 0), took at least 1 dose of study medication and had at least 1 central serum phosphorus value after the start of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196 (Placebo-controlled Withdrawal Period) | Change in Serum Phosphorus Levels From Baseline to Week 12 (LOCF) (ITT1) | -1.12 mg / dL | Standard Deviation 1.63 |
| Placebo (Placebo-controlled Withdrawal Period) | Change in Serum Phosphorus Levels From Baseline to Week 12 (LOCF) (ITT1) | -2.16 mg / dL | Standard Deviation 1.55 |