Chronic Kidney Disease Requiring Chronic Dialysis
Conditions
Keywords
PA21, Phosphate Binder
Brief summary
This is a Phase 3, randomised, active controlled, multicentre extension study to investigate the long-term safety and efficacy of PA21, a phosphate binder, for control of hyperphosphataemia in dialysis patients. This is an extension study to PA-CL-05A (NCT01324128), subjects have already been enrolled and have been treated with study medication for at least 24 weeks.
Interventions
Dose range of 5.0 g/day (2 tablets/day) to 15.0 g/day (6 tablets/day).
DRUGSevelamer carbonate
Film coated, compressed tablets. Dose range of 2.4 g/day (3 tablets/day) to 14.4 g/day (18 tablets/day).
Sponsors
Fresenius Medical Care North America
Vifor Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects who have completed treatment in Protocol PA-CL-05A * Written Informed Consent
Exclusion criteria
* Hyper/hypo calcemia; hyper intact parathyroid hormone (iPTH) * Other significant medical conditions * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Every 4 weeks from baseline to Week 28 | Endpoint is Week 28 or the latest available measurement after baseline when Week 28 data is missing. |
| Change From Baseline and Levels at Each Time Point for Serum Calcium | Every 4 weeks from baseline to Week 28 | Endpoint is Week 28 or the latest available measurement after baseline when Week 28 data is missing. |
| Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Every 4 weeks from baseline to Week 28 | Endpoint is Week 28 or the latest available measurement after baseline when Week 28 data is missing. |
Countries
Austria, Belgium, Croatia, Czechia, Germany, Latvia, Lithuania, Poland, Romania, Russia, Serbia, South Africa, Ukraine, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PA21 PA21 (2.5 g tablet). Dose range of 5.0 g/day (2 tablets/day) to 15.0 g/day (6 tablets/day). | 391 |
| Sevelamer Carbonate Sevelamer carbonate. Dose range of 2.4 g/day (3 tablets/day) to 14.4 g/day (18 tablets/day). | 268 |
| Total | 659 |
Baseline characteristics
| Characteristic | PA21 | Sevelamer Carbonate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 95 Participants | 78 Participants | 173 Participants |
| Age, Categorical Between 18 and 65 years | 296 Participants | 190 Participants | 486 Participants |
| Age, Continuous | 55.2 years STANDARD_DEVIATION 13.2 | 55.6 years STANDARD_DEVIATION 14.58 | 55.4 years STANDARD_DEVIATION 13.77 |
| Region of Enrollment Croatia | 16 participants | 8 participants | 24 participants |
| Region of Enrollment Europe | 85 participants | 49 participants | 134 participants |
| Region of Enrollment Russian Federation | 65 participants | 44 participants | 109 participants |
| Region of Enrollment Serbia | 37 participants | 18 participants | 55 participants |
| Region of Enrollment South Africa | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Ukraine | 32 participants | 15 participants | 47 participants |
| Region of Enrollment United States | 154 participants | 133 participants | 287 participants |
| Sex: Female, Male Female | 171 Participants | 102 Participants | 273 Participants |
| Sex: Female, Male Male | 220 Participants | 166 Participants | 386 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 208 / 391 | 169 / 267 |
| serious Total, serious adverse events | 78 / 391 | 52 / 267 |
Outcome results
Primary
Change From Baseline and Levels at Each Time Point for Serum Calcium
Endpoint is Week 28 or the latest available measurement after baseline when Week 28 data is missing.
Time frame: Every 4 weeks from baseline to Week 28
Population: For the Primary Outcome, data from the Full Analysis Set for PA-CL-05B (FAS5B) was used. The FAS5B consists of all subjects who enrolled in PA-CL-05B, received at least 1 dose of PA-CL-05B medication, and had at least 1 efficacy assessment after the PA-CL-05B study entry visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 4 (n = 346, 236 | -1.2 mg/dL | Standard Deviation 12.07 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 8 (n = 325, 238) | -1.2 mg/dL | Standard Deviation 12.3 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 12 (n = 321, 242) | 0.1 mg/dL | Standard Deviation 12.94 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 16 (n = 313, 228) | 0.5 mg/dL | Standard Deviation 14.04 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 20 (n = 300, 221) | 0.4 mg/dL | Standard Deviation 13.24 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 24 (n = 284, 207) | 1.1 mg/dL | Standard Deviation 13.57 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 28 (n = 286, 210) | 2.3 mg/dL | Standard Deviation 13.52 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Endpoint (n = 365, 258) | 1.5 mg/dL | Standard Deviation 13.86 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Endpoint (n = 365, 258) | 2.9 mg/dL | Standard Deviation 16.68 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 4 (n = 346, 236 | -0.8 mg/dL | Standard Deviation 13.37 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 20 (n = 300, 221) | 1.6 mg/dL | Standard Deviation 13.29 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 8 (n = 325, 238) | 1.5 mg/dL | Standard Deviation 14.4 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 28 (n = 286, 210) | 2.3 mg/dL | Standard Deviation 16.39 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 12 (n = 321, 242) | 1.9 mg/dL | Standard Deviation 13.79 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 24 (n = 284, 207) | 2.2 mg/dL | Standard Deviation 15.74 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Calcium | Change from Baseline to Week 16 (n = 313, 228) | 2.0 mg/dL | Standard Deviation 16.05 |
Primary
Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH)
Endpoint is Week 28 or the latest available measurement after baseline when Week 28 data is missing.
Time frame: Every 4 weeks from baseline to Week 28
Population: For the Primary Outcome, data from the Full Analysis Set for PA-CL-05B (FAS5B) was used. The FAS5B consists of all subjects who enrolled in PA-CL-05B, received at least 1 dose of PA-CL-05B medication, and had at least 1 efficacy assessment after the PA-CL-05B study entry visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 4 (n = 365, 252) | 11.8 pg/mL | Standard Deviation 177.39 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 8 (n = 362, 258) | 8.6 pg/mL | Standard Deviation 204.39 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 12 (n = 352, 252) | 28.9 pg/mL | Standard Deviation 315.81 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 16 (n = 341, 241) | 54.5 pg/mL | Standard Deviation 352.92 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 20 (n = 334, 236) | 28.0 pg/mL | Standard Deviation 233.13 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 24 (n = 320, 226) | 27.7 pg/mL | Standard Deviation 271.31 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 28 (n = 310, 222) | 53.0 pg/mL | Standard Deviation 287.19 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Endpoint (n = 381, 260) | 52.3 pg/mL | Standard Deviation 273.14 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Endpoint (n = 381, 260) | 67.5 pg/mL | Standard Deviation 270.06 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 4 (n = 365, 252) | 25.9 pg/mL | Standard Deviation 186.42 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 20 (n = 334, 236) | 72.1 pg/mL | Standard Deviation 228.03 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 8 (n = 362, 258) | 40.8 pg/mL | Standard Deviation 201.18 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 28 (n = 310, 222) | 71.5 pg/mL | Standard Deviation 278.03 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 12 (n = 352, 252) | 64.1 pg/mL | Standard Deviation 204.11 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 24 (n = 320, 226) | 79.6 pg/mL | Standard Deviation 253.65 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Intact Parathyroid Hormone (iPTH) | Change from Baseline to Week 16 (n = 341, 241) | 52.3 pg/mL | Standard Deviation 210.35 |
Primary
Change From Baseline and Levels at Each Time Point for Serum Phosphorus
Endpoint is Week 28 or the latest available measurement after baseline when Week 28 data is missing.
Time frame: Every 4 weeks from baseline to Week 28
Population: For the Primary Outcome, data from the Full Analysis Set for PA-CL-05B (FAS5B) was used. The FAS5B consists of all subjects who enrolled in PA-CL-05B, received at least 1 dose of PA-CL-05B medication, and had at least 1 efficacy assessment after the PA-CL-05B study entry visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 4 (n = 346, 236) | -0.2 mg/dL | Standard Deviation 1.33 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 8 (n = 325, 238) | -0.2 mg/dL | Standard Deviation 1.38 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 12 (n = 322, 242) | -0.0 mg/dL | Standard Deviation 1.43 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 16 (n = 313, 228) | 0.0 mg/dL | Standard Deviation 1.57 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 20 (n = 300, 221) | -0.0 mg/dL | Standard Deviation 1.46 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 24 (n = 286, 208) | 0.1 mg/dL | Standard Deviation 1.53 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Chnage from Baseline to Week 28 (n = 287, 210) | 0.2 mg/dL | Standard Deviation 1.52 |
| PA21 | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Endpoint (n = 384, 260) | 0.1 mg/dL | Standard Deviation 1.62 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Endpoint (n = 384, 260) | 0.3 mg/dL | Standard Deviation 1.79 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 4 (n = 346, 236) | -0.1 mg/dL | Standard Deviation 1.47 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 20 (n = 300, 221) | 0.1 mg/dL | Standard Deviation 1.44 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 8 (n = 325, 238) | 0.1 mg/dL | Standard Deviation 1.56 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Chnage from Baseline to Week 28 (n = 287, 210) | 0.2 mg/dL | Standard Deviation 1.76 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 12 (n = 322, 242) | 0.2 mg/dL | Standard Deviation 1.55 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 24 (n = 286, 208) | 0.2 mg/dL | Standard Deviation 1.78 |
| Sevelamer Carbonate | Change From Baseline and Levels at Each Time Point for Serum Phosphorus | Change from Baseline to Week 16 (n = 313, 228) | 0.2 mg/dL | Standard Deviation 1.75 |