Chronic Kidney Disease, Dialysis, Hyperphosphatemia, Dyslipidemia
Conditions
Keywords
Chronic Kidney Disease, Dialysis, Hyperphosphatemia, Dyslipidemia, Phosphate binder
Brief summary
This is a phase III multi-centre study in two periods: the first period is a phosphate binder and lipid lowering drugs washout for 8 weeks, the second period is a double-blind, randomised, parallel group, fixed dose, for 12 weeks.
Interventions
DRUGMCI-196
3g to 15g/day (3 times a day), Tablet, 12 weeks of fixed dose of study
DRUGPlacebo
3g to 15g/day (3 times a day), Tablet, 12 weeks of fixed dose of study
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. * A a serum albumin level\<30.0g/L * A PTH level \>1000pg/mL * A body mass index (BMI)\<= 16.0kg/㎡ or =\>40.0kg/㎡ * A serum LDL-C level \>4.94mmol/L(190mg/dL) * A serum triglycerides level \>6.76mmol/L (600mg/dL) * A 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 |
|---|---|---|
| The Change in Serum Phosphorus | 12 weeks | The change from baseline to week 12 |
| The Change in LDL-cholesterol | 12 weeks | The percentage change from baseline to week 12 |
Secondary
| Measure | Time frame |
|---|---|
| The Change in Triglycerides | 12 weeks |
| The Change in PTH | 12 weeks |
| The Change in Total-cholesterol | 12 weeks |
| The Change in Ca x P Ion Product | 12 weeks |
| The Incidence of Adverse Events | 12 weeks |
| The Change in Ca | 12 weeks |
| The Change in HDL-cholesterol | 12 weeks |
Countries
Hungary, Italy, Malaysia, North Macedonia, Poland, Russia, Serbia, Ukraine
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-196: 3 g MCI-196: 3 g/ day | 104 |
| MCI-196: 6 g MCI-196: 6 g/ day | 102 |
| MCI-196: 9 g MCI-196: 9 g/ day | 98 |
| MCI-196: 12 g MCI-196: 12 g/ day | 102 |
| MCI-196: 15 g MCI-196: 15 g/ day | 101 |
| Pooled Placebo Placebo 9 tablets, 12 tablets and 15 tablets/ day | 132 |
| Total | 639 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 7 | 7 | 8 | 13 | 4 |
| Overall Study | Death | 0 | 0 | 1 | 2 | 1 | 2 |
| Overall Study | Lack of Efficacy | 32 | 12 | 10 | 13 | 7 | 31 |
| Overall Study | Other Reasons | 4 | 1 | 4 | 3 | 4 | 2 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 | 0 | 0 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 8 | 10 | 11 | 15 | 7 |
Baseline characteristics
| Characteristic | MCI-196: 3 g | MCI-196: 6 g | MCI-196: 9 g | MCI-196: 12 g | MCI-196: 15 g | Pooled Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 49.9 years STANDARD_DEVIATION 12.2 | 48.7 years STANDARD_DEVIATION 14.64 | 47.3 years STANDARD_DEVIATION 12.55 | 49.5 years STANDARD_DEVIATION 12.41 | 50.7 years STANDARD_DEVIATION 11.34 | 48.5 years STANDARD_DEVIATION 12.54 | 49.1 years STANDARD_DEVIATION 12.65 |
| Sex: Female, Male Female | 48 Participants | 54 Participants | 48 Participants | 48 Participants | 46 Participants | 55 Participants | 299 Participants |
| Sex: Female, Male Male | 56 Participants | 48 Participants | 50 Participants | 54 Participants | 55 Participants | 77 Participants | 340 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 104 | 44 / 102 | 49 / 98 | 53 / 102 | 59 / 101 | 65 / 132 |
| serious Total, serious adverse events | 3 / 104 | 1 / 102 | 2 / 98 | 7 / 102 | 5 / 101 | 8 / 132 |
Outcome results
Primary
The Change in LDL-cholesterol
The percentage change from baseline to week 12
Time frame: 12 weeks
Population: ITT: The ITT population included all subjects who received a randomisation number, took study medication, and had at least 1 central laboratory serum phosphorus or LDL-C value after the start of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196: 3 g | The Change in LDL-cholesterol | -16.66 Percent change | Standard Deviation 20.05 |
| MCI-196: 6 g | The Change in LDL-cholesterol | -23.56 Percent change | Standard Deviation 20.99 |
| MCI-196: 9 g | The Change in LDL-cholesterol | -27.64 Percent change | Standard Deviation 21.45 |
| MCI-196: 12 g | The Change in LDL-cholesterol | -29.44 Percent change | Standard Deviation 25.28 |
| MCI-196: 15 g | The Change in LDL-cholesterol | -27.46 Percent change | Standard Deviation 24.57 |
| Pooled Placebo | The Change in LDL-cholesterol | 2.77 Percent change | Standard Deviation 17.44 |
Primary
The Change in Serum Phosphorus
The change from baseline to week 12
Time frame: 12 weeks
Population: ITT: The ITT population included all subjects who received a randomisation number, took study medication, and had at least 1 central laboratory serum phosphorus or LDL-C value after the start
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196: 3 g | The Change in Serum Phosphorus | -0.23 mg/dL | Standard Deviation 1.62 |
| MCI-196: 6 g | The Change in Serum Phosphorus | -0.77 mg/dL | Standard Deviation 1.97 |
| MCI-196: 9 g | The Change in Serum Phosphorus | -0.97 mg/dL | Standard Deviation 1.68 |
| MCI-196: 12 g | The Change in Serum Phosphorus | -0.71 mg/dL | Standard Deviation 1.84 |
| MCI-196: 15 g | The Change in Serum Phosphorus | -1.41 mg/dL | Standard Deviation 1.43 |
| Pooled Placebo | The Change in Serum Phosphorus | -0.12 mg/dL | Standard Deviation 1.7 |
Secondary
The Change in Ca
Time frame: 12 weeks
Secondary
The Change in Ca x P Ion Product
Time frame: 12 weeks
Secondary
The Change in HDL-cholesterol
Time frame: 12 weeks
Secondary
The Change in PTH
Time frame: 12 weeks
Secondary
The Change in Total-cholesterol
Time frame: 12 weeks
Secondary
The Change in Triglycerides
Time frame: 12 weeks
Secondary
The Incidence of Adverse Events
Time frame: 12 weeks