Chronic Kidney Disease, Dialysis, Hyperphosphatemia
Conditions
Keywords
Chronic Kidney Disease, Dialysis, Hyperphosphatemia
Brief summary
This is a PIII multi-center, open-label, flexible dose, long-term safety study, that in conjunction with the E07(NCT00416520), E08(NCT00542386) and E09(NCT00451295) studies will allow exposure to MCI-196 for up to 52 weeks
Detailed description
Following completion of one of the Phase III studies (E07, E08 or E09) eligible patients will receive either MCI-196 for up to 52 weeks. The study is in two periods. The initial period allows flexible dosing for a period of 8 weeks. This will allow subjects to achieve individually optimised doses. After 8 weeks, subjects will continue flexible dosing with MCI-196 but with titration intervals every 4 weeks instead of every 2 weeks. Subjects previously exposed to MCI-196 will end the study at Week 40.
Interventions
DRUGMCI-196
3g to 15g/day (3 times a day), Tablet, 40 weeks of flexible dose
Current approved dosing recommendations for 12 weeks
Sponsors
Tanabe Pharma Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Clinically stable haemodialysis or peritoneal dialysis treatment. * Stable phosphate control * Stabilised phosphorus diet. * female subjects of child-bearing potential must have a negative serum pregnancy test. * Male subjects must agree to use appropriate contraception. * Completed one of the MCI-196 PIII studies
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. * Current or a history of significant gastrointestinal motility problems * Positive test for HIV 1 and 2 antibodies. * History of substance or alcohol abuse within the last year. * Seizure disorders. * History of drug or other allergy. * Temporary catheter with active signs of inflammation or infection. * The subject has participated in a clinical study with any experimental medication (with the exception of MCI-196 PIII studies) in the last 30days or experimental biological product within the 90 days prior to signing of informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Serum Phosphorus for MCI-196 and Sevelamer | 52 weeks (Baseline-52 weeks) | Change from Baseline to Week 52 (LOCF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percent Change in Serum LDL-cholesterol for MCI-196 and Sevelamer | 52 weeks (Baseline-52 weeks) | Percent Change from Baseline to Week 52 (LOCF) |
Countries
Austria, Czechia, France, Germany, Hungary, Italy, Malaysia, North Macedonia, Poland, Russia, Serbia, South Africa, Spain, Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-196 From E07 / E08 Studies 3, 6, 9, 12, or 15g / day as titrated | 432 |
| MCI-196 From E07 Study 3, 6, 9, 12, or 15g / day as titrated | 76 |
| Sevelamer From E07 Study 2.4, 4.8, 7.2, 9.6, or 12.0g / day as titrated | 124 |
| Total | 632 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 19 | 6 | 9 |
| Overall Study | Death | 10 | 7 | 3 |
| Overall Study | Lack of Efficacy | 9 | 2 | 0 |
| Overall Study | Other reasons | 24 | 10 | 10 |
| Overall Study | Physician Decision | 2 | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 41 | 5 | 8 |
Baseline characteristics
| Characteristic | MCI-196 From E07 / E08 Studies | MCI-196 From E07 Study | Sevelamer From E07 Study | Total |
|---|---|---|---|---|
| Age, Customized <65 years | 374 participants | 55 participants | 77 participants | 506 participants |
| Age, Customized >=65 years | 58 participants | 21 participants | 47 participants | 126 participants |
| Sex: Female, Male Female | 203 Participants | 25 Participants | 53 Participants | 281 Participants |
| Sex: Female, Male Male | 229 Participants | 51 Participants | 71 Participants | 351 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 | 310 / 432 | 75 / 76 | 112 / 124 |
| serious Total, serious adverse events | 74 / 432 | 31 / 76 | 48 / 124 |
Outcome results
Primary
The Change in Serum Phosphorus for MCI-196 and Sevelamer
Change from Baseline to Week 52 (LOCF)
Time frame: 52 weeks (Baseline-52 weeks)
Population: ITT2 population included all subjects who received enrolment number into MCI-196-E10, took at least 1 dose of study medication in original study and had at least 1 post-enrolment efficacy value after start of study medication in MCI-196-E10. Data collected from start of original studies to end of MCI-196-E10 were analysed for this population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196 From E07 / E08 Studies | The Change in Serum Phosphorus for MCI-196 and Sevelamer | -1.23 mg / dL | Standard Deviation 1.78 |
| MCI-196 From E07 Study | The Change in Serum Phosphorus for MCI-196 and Sevelamer | -1.47 mg / dL | Standard Deviation 1.68 |
| Sevelamer From E07 Study | The Change in Serum Phosphorus for MCI-196 and Sevelamer | -2.26 mg / dL | Standard Deviation 1.82 |
Secondary
The Percent Change in Serum LDL-cholesterol for MCI-196 and Sevelamer
Percent Change from Baseline to Week 52 (LOCF)
Time frame: 52 weeks (Baseline-52 weeks)
Population: ITT2 population included all subjects who received enrolment number into MCI-196-E10, took at least 1 dose of study medication in original study and had at least 1 post-enrolment efficacy value after start of study medication in MCI-196-E10. Data collected from start of original studies to end of MCI-196-E10 were analysed for this population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196 From E07 / E08 Studies | The Percent Change in Serum LDL-cholesterol for MCI-196 and Sevelamer | -26.22 percentage change of LDL-cholesterol | Standard Deviation 27.08 |
| MCI-196 From E07 Study | The Percent Change in Serum LDL-cholesterol for MCI-196 and Sevelamer | -30.62 percentage change of LDL-cholesterol | Standard Deviation 20.12 |
| Sevelamer From E07 Study | The Percent Change in Serum LDL-cholesterol for MCI-196 and Sevelamer | -28.66 percentage change of LDL-cholesterol | Standard Deviation 23.61 |