Chronic Kidney Disease Requiring Chronic Dialysis
Conditions
Keywords
PA21, Phosphate Binder
Brief summary
This is a Phase 3, randomised, active controlled, multicentre study to investigate the safety and efficacy of PA21, a phosphate binder, for control of hyperphosphataemia in dialysis patients. The primary objective is to establish the efficacy of PA21 for lowering phosphate levels in these patients.
Interventions
Dose range of 5.0 g/day (2 tablets/day) to 15.0 g/day (6 tablets/day).
DRUGSevelamer carbonate
Dose range of 2.4 g/day (3 tablets/day) to 14.4 g/day (18 tablets/day)
DRUGPA21-1 (1.25 g tablet containing 250 mg iron)
Low dose comparator (1.25 g/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
* Dialysis patients with hyperphosphataemia (≥ 1.94 mmol/L; ≥ 6.0 mg/dL) * Stable dose of phosphate binder * 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 in Serum Phosphorus Levels From Week 24 to Week 27 | Week 24, Week 27 | Change in serum phosphorus levels compared between PA21 Maintenance Dose (MD) and PA21-1 Low Dose (LD) in Stage 2 from Week 24 to Week 27 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Phosphorus Levels From Baseline to Week 12 | Week 12 post Baseline | Change in serum phosphorus levels from baseline to Week 12 in the PA21 group versus the sevelamer group. |
Countries
Austria, Belgium, Croatia, Czechia, Germany, Latvia, Lithuania, Poland, Romania, Russia, Serbia, South Africa, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The first 100HD subjects that completed Stage 1 in the PA21 treatment group entered Stage 2 and were randomised to PA21 Maintenance Dose (MD) or PA21-1 Low Dose (LD). Due to a randomisation error only 99 subjects were randomised into Stage 2.
Participants by arm
| Arm | Count |
|---|---|
| PA21 Stage 1 PA21 (2.5 g tablet). Dose range of 5.0 g/day (2 tablets/day) to 15.0 g/day (6 tablets/day). | 710 |
| Sevelamer Carbonate Stage 1 Sevelamer carbonate. Dose range of 2.4 g/day (3 tablets/day) to 14.4 g/day (18 tablets/day). | 349 |
| Total | 1,059 |
Baseline characteristics
| Characteristic | PA21 Stage 1 | Sevelamer Carbonate Stage 1 | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 198 Participants | 107 Participants | 305 Participants |
| Age, Categorical Between 18 and 65 years | 512 Participants | 242 Participants | 754 Participants |
| Age, Continuous | 56.3 years STANDARD_DEVIATION 13.35 | 55.8 years STANDARD_DEVIATION 14.59 | 56.2 years STANDARD_DEVIATION 13.77 |
| Region of Enrollment Croatia | 19 participants | 8 participants | 27 participants |
| Region of Enrollment Europe | 159 participants | 77 participants | 236 participants |
| Region of Enrollment Russian Federation | 101 participants | 50 participants | 151 participants |
| Region of Enrollment Serbia | 47 participants | 24 participants | 71 participants |
| Region of Enrollment South Africa | 5 participants | 2 participants | 7 participants |
| Region of Enrollment Ukraine | 34 participants | 17 participants | 51 participants |
| Region of Enrollment United States | 345 participants | 171 participants | 516 participants |
| Sex: Female, Male Female | 314 Participants | 129 Participants | 443 Participants |
| Sex: Female, Male Male | 396 Participants | 220 Participants | 616 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 426 / 707 | 162 / 348 | 10 / 49 | 2 / 45 |
| serious Total, serious adverse events | 129 / 707 | 69 / 348 | 6 / 49 | 2 / 45 |
Outcome results
Primary
Change in Serum Phosphorus Levels From Week 24 to Week 27
Change in serum phosphorus levels compared between PA21 Maintenance Dose (MD) and PA21-1 Low Dose (LD) in Stage 2 from Week 24 to Week 27
Time frame: Week 24, Week 27
Population: For the Primary Outcome, data from the Primary Efficacy Set (PES) was used. The PES consists of subjects who were randomized to Stage 2 and received at least 1 dose of study medication during Stage 2 and had at least 1 post-baseline (Stage 2) efficacy assessment in Stage 2.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PA21 (MD) Stage 2 | Change in Serum Phosphorus Levels From Week 24 to Week 27 | 0.25 mg/dL | Standard Deviation 0.23 |
| PA21-1 (LD) Stage 2 | Change in Serum Phosphorus Levels From Week 24 to Week 27 | 1.92 mg/dL | Standard Deviation 0.23 |
Secondary
Change in Serum Phosphorus Levels From Baseline to Week 12
Change in serum phosphorus levels from baseline to Week 12 in the PA21 group versus the sevelamer group.
Time frame: Week 12 post Baseline
Population: For the Secondary Outcome, data from the Per Protocol Set (PPS) was used. The PPS consists of all subjects who had completed the analysis dose titration period (baseline to Week 12), had at least 1 evaluable serum phosphorus result at or after Week 12, and had no major protocol deviations.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PA21 (MD) Stage 2 | Change in Serum Phosphorus Levels From Baseline to Week 12 | -2.19 mg/dL | Standard Error 0.09 |
| PA21-1 (LD) Stage 2 | Change in Serum Phosphorus Levels From Baseline to Week 12 | -2.45 mg/dL | Standard Error 0.11 |