Chronic Kidney Disease
Conditions
Keywords
Hemodialysis
Brief summary
The purpose of this study is to investigate the ability of different doses of PA21 to lower serum phosphate levels, in patients with chronic kidney disease on maintenance hemodialysis.
Interventions
DRUG1.25 g PA21 (250 mg iron)
Daily dose of 1.25 g PA21 (1 tablet/day) for 6 weeks. One PA21 tablet will be taken orally with the largest meal of the day.
DRUG5.0 g PA21 (1,000 mg iron)
Daily dose of 5.0 g PA21 (4 tablets/day) for 6 weeks. Two PA21 tablets will be taken orally with the largest meal of the day, and one PA21 tablet will be taken orally with each of the two smaller main meals of the day (3 meals per day).
DRUG7.5 g PA21 (1,500 mg iron)
Daily dose of 7.5 g PA21 (6 tablets/day) for 6 weeks. Two PA21 tablets will be taken orally with each of the three main meals of the day (3 meals per day).
DRUG10.0 g PA21 (2,000 mg iron)
Daily dose of 10.0 g PA21 (8 tablets/day) for 6 weeks. Four PA21 tablets will be taken orally with the largest meal of the day, and two PA21 tablets will be taken orally with each of the two smaller main meals of the day (3 meals per day).
DRUG12.5 g PA21 (2,500 mg iron)
Daily dose of 12.5 g PA21 (10 tablets/day) for 6 weeks. Four tablets will be taken orally with the largest meal of the day, and three PA21 tablets will be taken orally with each of the two smaller main meals of the day (3 meals per day).
Daily dose of 4.8 g Sevelamer hydrochloride (6 tablets/day) for 6 weeks. Two Sevelamer tablets will be taken orally with each of the three main meals of the day (3 meals per day).
Sponsors
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
Main Inclusion Criteria: * ≥ 18 years of age, * Receiving stable maintenance hemodialysis 3 times a week * On restricted phosphate diet at screening and throughout study * Receiving stable dose of phosphate binder for at least 1 month * Serum phosphate levels \>1.78 mmol/L Main
Exclusion criteria
* Uncontrolled hyperphosphatemia * Hypercalcemia at screening or during washout * Serum calcium \< 1.9 mmol/L (\<7.6 mg/dL) * Severe hyperparathyroidism (iPTH levels \>600 ng/L) * Pregnancy or lactation * Iron deficiency anemia * History of hemochromatosis or ferritin \>800 mg/L, * Hepatitis B, hepatitis C or other significant concurrent liver disorders * Known positivity to HIV * Use of oral iron preparations 1 month before screening, * Serious medical condition or uncontrolled systemic disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Serum-phosphate Levels at the End of Treatment. | 6 weeks after baseline |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Serum-phosphate Levels at Week 2 | 2 weeks after baseline |
| Change From Baseline in Serum-phosphate Levels at Week 4 | 4 weeks after baseline |
| Change From Baseline in Serum-phosphate Levels at Week 5 | 5 weeks after baseline |
Countries
Bulgaria, Croatia, Czechia, Germany, Poland, Romania, Russia, Switzerland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1.25 g PA21 (250 mg Iron) Daily dose of 1.25 g PA21 (1 tablet) | 26 |
| 5.0 g PA21 (1,000 mg Iron) Daily dose of 5.0 g PA21 (4 tablets) | 26 |
| 7.5 g PA21 (1,500 mg Iron) Daily dose of 7.5 g PA21 (6 tablets) | 25 |
| 10.0 g PA21 (2,000 mg Iron) Daily dose of 10.0g PA21 (8 tablets) | 27 |
| 12.5g PA21 (2,500 mg Iron) Daily dose of 12.5 g PA21 (10 tablets) | 24 |
| Sevelamer Hydrochloride - Active Control Daily dose of 4.8 g sevelamer hydrochloride (6 tablets) | 26 |
| Total | 154 |
Baseline characteristics
| Characteristic | 5.0 g PA21 (1,000 mg Iron) | 7.5 g PA21 (1,500 mg Iron) | 1.25 g PA21 (250 mg Iron) | 10.0 g PA21 (2,000 mg Iron) | 12.5g PA21 (2,500 mg Iron) | Sevelamer Hydrochloride - Active Control | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 11 Participants | 12 Participants | 10 Participants | 10 Participants | 10 Participants | 61 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 14 Participants | 14 Participants | 17 Participants | 14 Participants | 16 Participants | 93 Participants |
| Age, Continuous | 59.7 years STANDARD_DEVIATION 13.8 | 61.9 years STANDARD_DEVIATION 13.71 | 60.1 years STANDARD_DEVIATION 12.29 | 60.6 years STANDARD_DEVIATION 12.74 | 59.3 years STANDARD_DEVIATION 12.32 | 61.1 years STANDARD_DEVIATION 11 | 60.5 years STANDARD_DEVIATION 12.5 |
| Region of Enrollment Bulgaria | 3 participants | 5 participants | 3 participants | 4 participants | 7 participants | 1 participants | 23 participants |
| Region of Enrollment Croatia | 3 participants | 9 participants | 5 participants | 8 participants | 8 participants | 7 participants | 40 participants |
| Region of Enrollment Czech Republic | 3 participants | 0 participants | 0 participants | 0 participants | 3 participants | 2 participants | 8 participants |
| Region of Enrollment Germany | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 2 participants |
| Region of Enrollment Poland | 2 participants | 3 participants | 4 participants | 2 participants | 0 participants | 4 participants | 15 participants |
| Region of Enrollment Romania | 4 participants | 2 participants | 2 participants | 3 participants | 1 participants | 0 participants | 12 participants |
| Region of Enrollment Russian Federation | 5 participants | 3 participants | 7 participants | 5 participants | 2 participants | 6 participants | 28 participants |
| Region of Enrollment Switzerland | 2 participants | 0 participants | 0 participants | 1 participants | 1 participants | 1 participants | 5 participants |
| Region of Enrollment United States | 4 participants | 3 participants | 4 participants | 4 participants | 2 participants | 4 participants | 21 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 9 Participants | 10 Participants | 11 Participants | 11 Participants | 57 Participants |
| Sex: Female, Male Male | 19 Participants | 16 Participants | 17 Participants | 17 Participants | 13 Participants | 15 Participants | 97 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 26 | 16 / 26 | 13 / 25 | 18 / 27 | 17 / 24 | 13 / 26 |
| serious Total, serious adverse events | 2 / 26 | 2 / 26 | 1 / 25 | 1 / 27 | 2 / 24 | 2 / 26 |
Outcome results
Primary
Change From Baseline in Serum-phosphate Levels at the End of Treatment.
Time frame: 6 weeks after baseline
Population: For the Primary Outcome, data from the Full Analysis Set (FAS) was used. The FAS consists of all randomised subjects who received at least 1 dose of study treatment and had at least 1 post-baseline efficacy evaluation (while on treatment).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 g PA21 (250 mg Iron) | Change From Baseline in Serum-phosphate Levels at the End of Treatment. | -0.042 mmol/L | Standard Deviation 0.65 |
| 5.0 g PA21 (1,000 mg Iron) | Change From Baseline in Serum-phosphate Levels at the End of Treatment. | -0.348 mmol/L | Standard Deviation 0.684 |
| 7.5 g PA21 (1,500 mg Iron) | Change From Baseline in Serum-phosphate Levels at the End of Treatment. | -0.404 mmol/L | Standard Deviation 0.391 |
| 10.0 g PA21 (2,000 mg Iron) | Change From Baseline in Serum-phosphate Levels at the End of Treatment. | -0.644 mmol/L | Standard Deviation 0.551 |
| 12.5g PA21 (2,500 mg Iron) | Change From Baseline in Serum-phosphate Levels at the End of Treatment. | -0.547 mmol/L | Standard Deviation 0.584 |
| Sevelamer Hydrochloride - Active Control | Change From Baseline in Serum-phosphate Levels at the End of Treatment. | -0.341 mmol/L | Standard Deviation 0.436 |
Secondary
Change From Baseline in Serum-phosphate Levels at Week 2
Time frame: 2 weeks after baseline
Population: For this Secondary Outcome, FAS was used, which consists of all randomized subjects who received at least 1 dose of study treatment and had at least 1 post-baseline efficacy evaluation (while on treatment).~Number of participants analyzed at this time point includes all subjects that had serum-phosphate measured at Week 2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 g PA21 (250 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 2 | -0.03 mmol/L | Standard Deviation 0.55 |
| 5.0 g PA21 (1,000 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 2 | -0.36 mmol/L | Standard Deviation 0.35 |
| 7.5 g PA21 (1,500 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 2 | -0.41 mmol/L | Standard Deviation 0.4 |
| 10.0 g PA21 (2,000 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 2 | -0.47 mmol/L | Standard Deviation 0.62 |
| 12.5g PA21 (2,500 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 2 | -0.46 mmol/L | Standard Deviation 0.45 |
| Sevelamer Hydrochloride - Active Control | Change From Baseline in Serum-phosphate Levels at Week 2 | -0.41 mmol/L | Standard Deviation 0.44 |
Secondary
Change From Baseline in Serum-phosphate Levels at Week 4
Time frame: 4 weeks after baseline
Population: For this Secondary Outcome, FAS was used, which consists of all randomized subjects who received at least 1 dose of study treatment and had at least 1 post-baseline efficacy evaluation (while on treatment).~Number of participants analyzed at this time point includes all subjects that had serum-phosphate measured at Week 4.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 g PA21 (250 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 4 | -0.03 mmol/L | Standard Deviation 0.39 |
| 5.0 g PA21 (1,000 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 4 | -0.39 mmol/L | Standard Deviation 0.45 |
| 7.5 g PA21 (1,500 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 4 | -0.32 mmol/L | Standard Deviation 0.54 |
| 10.0 g PA21 (2,000 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 4 | -0.58 mmol/L | Standard Deviation 0.53 |
| 12.5g PA21 (2,500 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 4 | -0.53 mmol/L | Standard Deviation 0.48 |
| Sevelamer Hydrochloride - Active Control | Change From Baseline in Serum-phosphate Levels at Week 4 | -0.53 mmol/L | Standard Deviation 0.35 |
Secondary
Change From Baseline in Serum-phosphate Levels at Week 5
Time frame: 5 weeks after baseline
Population: For this Secondary Outcome, FAS population was used, which consists of all randomized subjects who received at least 1 dose of study treatment and had at least 1 post-baseline efficacy evaluation (while on treatment).~Number of participants analyzed at this time point includes all subjects that had a serum-phosphate measurement at Week 5.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 1.25 g PA21 (250 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 5 | -0.05 mmol/L | Standard Deviation 0.62 |
| 5.0 g PA21 (1,000 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 5 | -0.51 mmol/L | Standard Deviation 0.62 |
| 7.5 g PA21 (1,500 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 5 | -0.40 mmol/L | Standard Deviation 0.33 |
| 10.0 g PA21 (2,000 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 5 | -0.57 mmol/L | Standard Deviation 0.55 |
| 12.5g PA21 (2,500 mg Iron) | Change From Baseline in Serum-phosphate Levels at Week 5 | -0.58 mmol/L | Standard Deviation 0.58 |
| Sevelamer Hydrochloride - Active Control | Change From Baseline in Serum-phosphate Levels at Week 5 | -0.52 mmol/L | Standard Deviation 0.37 |