Kidney Failure, Chronic
Conditions
Keywords
Chronic Kidney Disease, Phosphate Binder, Phosphate, Hyperphosphatemia
Brief summary
The purpose of this clinical study is to compare the effects of Genz-644470 with the effects of placebo and sevelamer carbonate (Renvela®) on the reduction of serum phosphorus in hyperphosphatemic chronic kidney disease participants on hemodialysis.
Interventions
DRUGPlacebo
DRUGGenz-644470
DRUGSevelamer carbonate
Sponsors
Genzyme, a Sanofi Company
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
* Serum phosphate level greater than (\>) 5.5 milligram per deciliter (mg/dL) (1.78 millimole per liter \[mmol/L\]) after discontinuation of current phosphate binder therapy * Men or women 18 years or older
Exclusion criteria
* Have active dysphagia or swallowing disorder or a predisposition to or current bowel obstruction, ileus, or severe gastrointestinal motility disorders including severe constipation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Placebo) | Baseline, Day 22 |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Sevelamer Carbonate) | Baseline, Day 22 |
| Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22 | Baseline, Day 22 |
| Change From Baseline in Total Cholesterol at Day 22 | Baseline, Day 22 |
| Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22 | Baseline, Day 22 |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
The study was conducted at 64 centers in the United States between 11 February 2009 and 20 August 2009.
Pre-assignment details
A total of 670 participants were screened of which 321 were screen failure and 349 participants were randomized. After screening, participants entered a two-week phosphate binder washout period prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matched to Genz-644470 tablet orally TID with meals for 3 weeks. | 50 |
| Genz-644470 2.4 g/Day Genz-644470 2.4 g/day tablets dosed orally TID with meals for 3 weeks. | 49 |
| Genz-644470 4.8 g/Day Genz-644470 4.8 g/day tablets dosed orally TID with meals for 3 weeks. | 48 |
| Genz-644470 7.2 g/Day Genz-644470 7.2 g/day tablets dosed orally TID with meals for 3 weeks. | 50 |
| Sevelamer Carbonate 2.4 g/Day Sevelamer Carbonate 2.4 g/day tablets dosed orally TID with meals for 3 weeks. | 50 |
| Sevelamer Carbonate 4.8 g/Day Sevelamer Carbonate 4.8 g/day tablets dosed orally TID with meals for 3 weeks. | 51 |
| Sevelamer Carbonate 7.2 g/Day Sevelamer Carbonate 7.2 g/day tablets dosed orally TID with meals for 3 weeks. | 48 |
| Total | 346 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 | 3 | 1 | 1 |
| Overall Study | Noncompliant | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Other | 2 | 0 | 2 | 0 | 0 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 0 | 4 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Genz-644470 2.4 g/Day | Genz-644470 4.8 g/Day | Genz-644470 7.2 g/Day | Sevelamer Carbonate 2.4 g/Day | Sevelamer Carbonate 4.8 g/Day | Sevelamer Carbonate 7.2 g/Day | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.1 years STANDARD_DEVIATION 13.6 | 58.3 years STANDARD_DEVIATION 12 | 54.7 years STANDARD_DEVIATION 11.3 | 56.7 years STANDARD_DEVIATION 13.3 | 54.6 years STANDARD_DEVIATION 13.4 | 56.6 years STANDARD_DEVIATION 11.9 | 53.6 years STANDARD_DEVIATION 13.1 | 56.2 years STANDARD_DEVIATION 12.7 |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 1 participants | 1 participants | 2 participants | 0 participants | 2 participants | 8 participants |
| Race/Ethnicity, Customized Black or African American | 21 participants | 20 participants | 25 participants | 25 participants | 23 participants | 25 participants | 22 participants | 161 participants |
| Race/Ethnicity, Customized Other | 0 participants | 0 participants | 0 participants | 2 participants | 0 participants | 1 participants | 1 participants | 4 participants |
| Race/Ethnicity, Customized White | 29 participants | 27 participants | 22 participants | 22 participants | 25 participants | 25 participants | 23 participants | 173 participants |
| Serum Phosphorus Level Greater Than or Equal to (>=) 7.0 mg/dL | 28 participants | 27 participants | 27 participants | 29 participants | 28 participants | 31 participants | 31 participants | 201 participants |
| Serum Phosphorus Level less than (<) 7.0 milligram per deciliter (mg/dL) | 22 participants | 22 participants | 21 participants | 21 participants | 22 participants | 20 participants | 17 participants | 145 participants |
| Sex: Female, Male Female | 20 Participants | 24 Participants | 23 Participants | 19 Participants | 22 Participants | 21 Participants | 15 Participants | 144 Participants |
| Sex: Female, Male Male | 30 Participants | 25 Participants | 25 Participants | 31 Participants | 28 Participants | 30 Participants | 33 Participants | 202 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 | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 50 | 17 / 49 | 17 / 48 | 25 / 50 | 22 / 50 | 25 / 51 | 22 / 48 |
| serious Total, serious adverse events | 4 / 50 | 2 / 49 | 6 / 48 | 6 / 50 | 8 / 50 | 5 / 51 | 5 / 48 |
Outcome results
Primary
Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Placebo)
Time frame: Baseline, Day 22
Population: Full Analysis Set (FAS) included all participants who received at least one dose of study drug and had baseline and at least one post-baseline phosphorus measure less than or equal to (\<=) 3 days after date of last study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Placebo) | -0.0 mg/dL | Standard Deviation 1.3 |
| Genz-644470 2.4 g/Day | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Placebo) | -0.6 mg/dL | Standard Deviation 1.5 |
| Genz-644470 4.8 g/Day | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Placebo) | -1.2 mg/dL | Standard Deviation 1.6 |
| Genz-644470 7.2 g/Day | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Placebo) | -1.8 mg/dL | Standard Deviation 1.9 |
Comparison: Analysis was performed using Wilcoxon rank sum tests.p-value: 0.0249Wilcoxon Rank Sum Tests
Comparison: Analysis was performed using Wilcoxon rank sum tests.p-value: 0.0001Wilcoxon Rank Sum Tests
Comparison: Analysis was performed using Wilcoxon rank sum tests.p-value: <0.0001Wilcoxon Rank Sum Tests
Secondary
Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22
Time frame: Baseline, Day 22
Population: Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22 | -1.3 mg/dL | Standard Deviation 17.4 |
| Genz-644470 2.4 g/Day | Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22 | -15.4 mg/dL | Standard Deviation 19.8 |
| Genz-644470 4.8 g/Day | Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22 | -13.2 mg/dL | Standard Deviation 18.6 |
| Genz-644470 7.2 g/Day | Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22 | -21.9 mg/dL | Standard Deviation 23.5 |
| Sevelamer Carbonate 4.8 g/Day | Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22 | -7.5 mg/dL | Standard Deviation 13 |
| Sevelamer Carbonate 7.2 g/Day | Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22 | -17.7 mg/dL | Standard Deviation 14.8 |
| Sevelamer Carbonate 7.2 g/Day | Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol at Day 22 | -22.6 mg/dL | Standard Deviation 24.5 |
Secondary
Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22
Time frame: Baseline, Day 22
Population: Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22 | -0.1 mg^2/dL^2 | Standard Deviation 12.7 |
| Genz-644470 2.4 g/Day | Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22 | -4.5 mg^2/dL^2 | Standard Deviation 12.3 |
| Genz-644470 4.8 g/Day | Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22 | -9.2 mg^2/dL^2 | Standard Deviation 14.7 |
| Genz-644470 7.2 g/Day | Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22 | -16.1 mg^2/dL^2 | Standard Deviation 16.1 |
| Sevelamer Carbonate 4.8 g/Day | Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22 | -8.3 mg^2/dL^2 | Standard Deviation 17.4 |
| Sevelamer Carbonate 7.2 g/Day | Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22 | -10.3 mg^2/dL^2 | Standard Deviation 17.5 |
| Sevelamer Carbonate 7.2 g/Day | Change From Baseline in Serum Calcium (Albumin-adjusted)-Phosphorus Product at Week 22 | -17.5 mg^2/dL^2 | Standard Deviation 13.4 |
Secondary
Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Sevelamer Carbonate)
Time frame: Baseline, Day 22
Population: FAS included all participants who received at least one dose of study drug and had baseline and at least one post-baseline phosphorus measure \<= 3 days after date of last study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Sevelamer Carbonate) | -0.6 mg/dL | Standard Deviation 1.5 |
| Genz-644470 2.4 g/Day | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Sevelamer Carbonate) | -1.2 mg/dL | Standard Deviation 1.6 |
| Genz-644470 4.8 g/Day | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Sevelamer Carbonate) | -1.8 mg/dL | Standard Deviation 1.9 |
| Genz-644470 7.2 g/Day | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Sevelamer Carbonate) | -0.9 mg/dL | Standard Deviation 1.7 |
| Sevelamer Carbonate 4.8 g/Day | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Sevelamer Carbonate) | -1.3 mg/dL | Standard Deviation 1.9 |
| Sevelamer Carbonate 7.2 g/Day | Change From Baseline in Serum Phosphorus at Day 22 (Genz-644470 vs Sevelamer Carbonate) | -2.0 mg/dL | Standard Deviation 1.4 |
Comparison: Analysis was performed using Wilcoxon rank sum tests.p-value: 0.2647Wilcoxon Rank Sum Tests
Comparison: Analysis was performed using Wilcoxon rank sum tests.p-value: 0.7944Wilcoxon Rank Sum Tests
Comparison: Analysis was performed using Wilcoxon rank sum tests.p-value: 0.3724Wilcoxon Rank Sum Tests
Secondary
Change From Baseline in Total Cholesterol at Day 22
Time frame: Baseline, Day 22
Population: Full Analysis Set.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Total Cholesterol at Day 22 | -3.8 mg/dL | Standard Deviation 20.9 |
| Genz-644470 2.4 g/Day | Change From Baseline in Total Cholesterol at Day 22 | -13.5 mg/dL | Standard Deviation 20.7 |
| Genz-644470 4.8 g/Day | Change From Baseline in Total Cholesterol at Day 22 | -11.2 mg/dL | Standard Deviation 19.7 |
| Genz-644470 7.2 g/Day | Change From Baseline in Total Cholesterol at Day 22 | -17.8 mg/dL | Standard Deviation 22.8 |
| Sevelamer Carbonate 4.8 g/Day | Change From Baseline in Total Cholesterol at Day 22 | -2.9 mg/dL | Standard Deviation 17.1 |
| Sevelamer Carbonate 7.2 g/Day | Change From Baseline in Total Cholesterol at Day 22 | -15.8 mg/dL | Standard Deviation 16.3 |
| Sevelamer Carbonate 7.2 g/Day | Change From Baseline in Total Cholesterol at Day 22 | -18.1 mg/dL | Standard Deviation 27.8 |