Chronic Kidney Disease
Conditions
Keywords
Chronic Kidney Disease, Dialysis, Dyslipidemia, Bile acid sequestrant
Brief summary
The primary objective of this study is to demonstrate the superiority of MCI-196 over placebo and non-inferiority with simvastatin in reducing serum low-density lipoprotein (LDL)-cholesterol in subjects with chronic kidney disease Stage V on dialysis. This study incorporates a Washout Period and two treatment periods - an active comparison phase and a placebo-controlled withdrawal phase.
Interventions
DRUGMCI-196
Tablets of 3 g to 12 g/day (3 times a day) with dose escalation design during 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)
Tablets once a day, for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)
DRUGSimvastatin
Tablets of 10 mg to 40 mg/day (once a day) with dose escalation design during 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)
DRUGPlacebo of MCI-196
Tablets 3 times a day for 16 weeks of Active Comparison Phase, and 4 weeks of fixed dose during Withdrawal Phase (Week 16 to Week 20)
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 undergoing regular dialysis treatment * If 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 him/her 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 \< 30 g/L * Triglycerides level \> 6.76 mmol/L (600 mg/dL) * LDL-cholesterol level \> 4.94 mmol/L (190 mg/dL) * A History of significant gastrointestinal motility problems * Biliary obstruction or proven liver dysfunction * A positive test for HIV 1 and 2 antibodies * A history of substance or alcohol abuse within the last year * The subject has a history of rhabdomyolysis or myopathy * Schedule to receive a kidney transplant within the next 6 months * The subject has porphyria * 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 |
|---|---|---|
| Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2) | week20 minus week16 | Percent Change from Week 16 to Week 20 (LOCF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Serum LDL-cholesterol Levels From Baseline to Week 16 (LOCF) (ITT1) | week16 minus week0 | Percent Change from Baseline to Week 16 (LOCF) |
| Change in Phosphorus(P), Calcium(Ca), Calcium-phosphorus Ion Product(PxCa) and Parathyroid Hormone (PTH) | 16 weeks and 20 weeks | — |
| Vital Signs, Adverse Events, and Laboratory Values | throughout study | — |
Countries
Belarus, Bulgaria, Croatia, Denmark, Indonesia, Israel, Italy, Latvia, Lithuania, Malaysia, Romania, Singapore, Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MCI-196 (Active) + Simvastatin (Placebo)/ Comparison Phase Active Comparison Phase: 3, 6, 9, 12g of MCI-196 / day as titrated
* There was a gap of 1 subject between STARTED and Overall Number of Baseline Participants.
* One subject (A) was randomised to simvastatin (active) group but was dispensed MCI-196 in error at Week 12. This subject was counted as STARTED of Simvastatin (Active) group but counted as Baseline Participants of MCI-196 (active) group. | 128 |
| Simvastatin (Active) + MCI-196 (Placebo)/ Comparion Phase Active Comparison Phase: 10 mg to 40 mg of Simvastatin / day as titrated
* There was a gap of 2 subject between STARTED and Overall Number of Baseline Participants.
* One subject did not take any study medication and excluded from Baseline Participants.
* In addition, one subject (A) was randomised to simvastatin (active) group but was dispensed MCI-196 in error at Week 12. This subject was counted as STARTED of Simvastatin (Active) group but counted as Baseline Participants of MCI-196 (active) group. | 131 |
| Total | 259 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Active Comparison Phase | Adverse Event | 14 | 0 | 0 | 9 | 0 | 0 |
| Active Comparison Phase | Death | 1 | 0 | 0 | 1 | 0 | 0 |
| Active Comparison Phase | Other Reasons | 1 | 0 | 0 | 1 | 0 | 0 |
| Active Comparison Phase | Physician Decision | 1 | 0 | 0 | 1 | 0 | 0 |
| Active Comparison Phase | Withdrawal by Subject | 7 | 0 | 0 | 6 | 0 | 0 |
| Placebo-controlled Withdrawal Phase | Death | 0 | 0 | 1 | 0 | 1 | 0 |
| Placebo-controlled Withdrawal Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | MCI-196 (Active) + Simvastatin (Placebo)/ Comparison Phase | Simvastatin (Active) + MCI-196 (Placebo)/ Comparion Phase | Total |
|---|---|---|---|
| Age, Continuous | 53.3 years STANDARD_DEVIATION 14.1 | 54.2 years STANDARD_DEVIATION 13.6 | 53.8 years STANDARD_DEVIATION 13.8 |
| Sex: Female, Male Female | 59 Participants | 61 Participants | 120 Participants |
| Sex: Female, Male Male | 69 Participants | 70 Participants | 139 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 89 / 128 | 87 / 131 |
| serious Total, serious adverse events | 16 / 128 | 12 / 131 |
Outcome results
Primary
Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2)
Percent Change from Week 16 to Week 20 (LOCF)
Time frame: week20 minus week16
Population: ITT2 population included all re-randomised subjects who completed 16 weeks in the active treatment groups (MCI-196 or simvastatin), received at least 1 dose of study medication in the Placebo-controlled withdrawal phase and had at least 1 central serum LDL-C value after Week 16.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196 (Active) + Simvastin (Placebo)/ Withdrawal Phase | Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2) | 4.03 Percent Change of LDL-cholesterol | Standard Deviation 19.92 |
| MCI-196 (Placebo) + Simvastin (Placebo)/ Withdrawal Phase | Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2) | 42.55 Percent Change of LDL-cholesterol | Standard Deviation 30.96 |
| Simvastin (Active) + MCI-196 (Placebo)/ Withdrawal Phase | Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2) | 2.76 Percent Change of LDL-cholesterol | Standard Deviation 18.43 |
| Simvastin (Placebo) + MCI-196 (Placebo)/ Withdrawal Phase | Percent Change in Serum LDL-cholesterol Levels From Week 16 to Week 20 (LOCF) (ITT2) | 49.84 Percent Change of LDL-cholesterol | Standard Deviation 41.89 |
Secondary
Change in Phosphorus(P), Calcium(Ca), Calcium-phosphorus Ion Product(PxCa) and Parathyroid Hormone (PTH)
Time frame: 16 weeks and 20 weeks
Secondary
Percent Change in Serum LDL-cholesterol Levels From Baseline to Week 16 (LOCF) (ITT1)
Percent Change from Baseline to Week 16 (LOCF)
Time frame: week16 minus week0
Population: ITT1 population included all subjects who received a randomisation number, took at least 1 dose of study medication and had at least 1 central serum LDL-C value after the start of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MCI-196 (Active) + Simvastin (Placebo)/ Withdrawal Phase | Percent Change in Serum LDL-cholesterol Levels From Baseline to Week 16 (LOCF) (ITT1) | -25.67 Percent Change of LDL-cholesterol | Standard Deviation 19.45 |
| MCI-196 (Placebo) + Simvastin (Placebo)/ Withdrawal Phase | Percent Change in Serum LDL-cholesterol Levels From Baseline to Week 16 (LOCF) (ITT1) | -26.38 Percent Change of LDL-cholesterol | Standard Deviation 22.9 |
Secondary
Vital Signs, Adverse Events, and Laboratory Values
Time frame: throughout study