Chronic Kidney Disease, Stage 5
Conditions
Brief summary
To compare the efficacy of Fosrenol (Lanthanum carbonate) and sevelamer hydrochloride in the reduction of serum phosphorus levels from baseline.
Detailed description
To compare the efficacy of Fosrenol (Lanthanum carbonate) and sevelamer hydrochloride in the reduction of serum phosphorus levels from baseline.
Interventions
DRUGFosrenol (Lanthanum Carbonate)
The starting dose is a total daily dose of 2250mg of Fosrenol (Lanthanum carbonate) to a maximum dose of 3000mg daily. Chewable tablets will be administered orally with meals in 750mg and 1000mg strength tablets.
The starting dose is a total daily dose of 4800mg of sevelamer hydrochloride up to a maximum of 6400 mg daily. Sevelamer hydrochloride 800mg tablets, administered orally with meals.
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults with end stage renal disease who are receiving dialysis
Exclusion criteria
* Subjects with significant gastrointestinal disorders * Subjects who are pregnant or nursing * Subjects currently taking lanthanum carbonate, sevelamer hydrochloride, cinacalcet hydrochloride * Subjects who are HIV positive * Subjects with clinical significant liver disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Serum Phosphorus Levels at 4 Weeks | 4 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Serum Calcium Levels at 4 Weeks | 4 weeks | — |
| Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks | Baseline and 4 weeks | — |
| Patients Achieving Kidney Disease Outcomes Quality Initiative (KDOQI) Target for Serum Phosphorous at 4 Weeks | 4 weeks | Kidney Disease Outcomes Quality Initiative (KDOQI) target for serum phosphorous is 3.5 - 5.5 mg/dL (1.13 - 1.77 mmol/L) |
Countries
Germany, Puerto Rico, United Kingdom, United States
Participant flow
Recruitment details
Following Washout 1, eligible subjects with serum phosphorus levels greater than or equal to 6.0mg/dL (greater than or equal to 1.94mmol/L) and calcium levels greater than or equal to 8.4mg/dL (greater than or equal to 2.10mmol/L) were randomized in a 1:1 ratio to receive either Fosrenol or sevelamer hydrochloride (HCl) for 4 weeks.
Pre-assignment details
The study consisted of the following phases: screening (1 week), washout 1 (2 weeks), treatment (4 weeks), Washout 2 (2 weeks), crossover treatment (4 weeks), and a 30-day follow-up
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population | 182 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 6 | 5 |
| First Intervention | Extended hospitalization | 1 | 0 |
| First Intervention | Kidney transplant | 1 | 1 |
| First Intervention | Lack of Efficacy | 2 | 0 |
| First Intervention | Protocol Violation | 2 | 2 |
| First Intervention | Site error | 1 | 0 |
| First Intervention | Sponsor's request | 1 | 0 |
| First Intervention | Subject exceeded safety criteria | 0 | 1 |
| First Intervention | Subject met an exclusionary criteria | 1 | 0 |
| First Intervention | Withdrawal by Subject | 3 | 3 |
| Second Intervention | Adverse Event | 5 | 2 |
| Second Intervention | Kidney Transplant | 1 | 1 |
| Second Intervention | Lack of Efficacy | 0 | 1 |
| Second Intervention | Protocol Violation | 4 | 1 |
| Second Intervention | Subject exceeded safety criteria | 1 | 0 |
| Second Intervention | Subject moved | 0 | 1 |
| Second Intervention | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 42 Participants |
| Age, Categorical Between 18 and 65 years | 140 Participants |
| Age, Continuous | 55.5 years STANDARD_DEVIATION 13.1 |
| Region of Enrollment Germany | 41 Participants |
| Region of Enrollment Puerto Rico | 1 Participants |
| Region of Enrollment United Kingdom | 1 Participants |
| Region of Enrollment United States | 139 Participants |
| Sex: Female, Male Female | 80 Participants |
| Sex: Female, Male Male | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 31 / 170 | 27 / 163 |
| serious Total, serious adverse events | 18 / 170 | 20 / 163 |
Outcome results
Primary
Change From Baseline in Serum Phosphorus Levels at 4 Weeks
Time frame: 4 weeks
Population: ITT population defined as subjects who were randomized, received at least one dose of investigational product, and had at least one post-dose assessment of the primary efficacy variable.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fosrenol | Change From Baseline in Serum Phosphorus Levels at 4 Weeks | -1.73 mg/dL | Standard Error 0.129 |
| Sevelamer HCl | Change From Baseline in Serum Phosphorus Levels at 4 Weeks | -1.44 mg/dL | Standard Error 0.132 |
p-value: 0.113ANCOVA
Secondary
Change From Baseline in Serum Calcium Levels at 4 Weeks
Time frame: 4 weeks
Population: ITT
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Fosrenol | Change From Baseline in Serum Calcium Levels at 4 Weeks | 0.06 mg/dL | Standard Error 0.045 |
| Sevelamer HCl | Change From Baseline in Serum Calcium Levels at 4 Weeks | -0.06 mg/dL | Standard Error 0.046 |
p-value: 0.0249ANCOVA
Secondary
Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks
Time frame: Baseline and 4 weeks
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Fosrenol | Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks | Baseline | 225.46 pg/mL | Standard Error 11.094 |
| Fosrenol | Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks | Endpoint | 296.48 pg/mL | Standard Error 17.412 |
| Sevelamer HCl | Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks | Baseline | 225.46 pg/mL | Standard Error 11.094 |
| Sevelamer HCl | Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks | Endpoint | 291.18 pg/mL | Standard Error 16.181 |
Secondary
Patients Achieving Kidney Disease Outcomes Quality Initiative (KDOQI) Target for Serum Phosphorous at 4 Weeks
Kidney Disease Outcomes Quality Initiative (KDOQI) target for serum phosphorous is 3.5 - 5.5 mg/dL (1.13 - 1.77 mmol/L)
Time frame: 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fosrenol | Patients Achieving Kidney Disease Outcomes Quality Initiative (KDOQI) Target for Serum Phosphorous at 4 Weeks | 42.7 Percentage of Participants |
| Sevelamer HCl | Patients Achieving Kidney Disease Outcomes Quality Initiative (KDOQI) Target for Serum Phosphorous at 4 Weeks | 34.6 Percentage of Participants |