Hyperphosphatemia
Conditions
Keywords
PA21, phosphate binder
Brief summary
This is a Phase 3, Open-label, Randomised, Active-controlled, Parallel Group, Multicentre Study to Investigate the Safety and Efficacy of PA21 (Velphoro®) and Calcium Acetate (Phoslyra®) in Paediatric and Adolescent CKD Patients with Hyperphosphataemia. The aim of this Phase 3 clinical study is to demonstrate similar efficacy of PA21 (Velphoro) in paediatric and adolescent patients with CKD, and to provide safety and dosing information for this patient population. The Phoslyra (comparator) group provides information for a descriptive comparison of PA21 against a commonly used calcium-based phosphate binder (calcium acetate).
Interventions
DRUGPA21 (Velphoro®)
During Stage 1 (Open-Label Dose Titration; up to 10 weeks), PA21 subjects will receive PA21 at a starting dose based on their age. Dose of PA21 will be increased or decreased as required for efficacy (to achieve age specific target serum phosphorus level), provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time. During Stage 2 (Open-Label Safety Extension, 24 week safety extension),subjects will continue on the dose received at the end of Stage 1, unless a dose change is required. Doses may be titrated for efficacy (to achieve age specific target Serum phosphorus levels), provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time during Stage 2.
DRUGCalcium Acetate (Phoslyra®)
During Stage 1 (Open-Label Dose Titration; up to 10 weeks), Phoslyra subjects will receive Phoslyra either at a starting dose based on their weight or, if considered more appropriate by the Investigator, at an equivalent dose of their previous phosphate binder (PB), calcium-based or sevelamer. Dose of Phoslyra will be increased or decreased as required for efficacy (to achieve age specific target serum phosphorus level), provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time. During Stage 2 (Open-Label Safety Extension, 24 week safety extension),subjects will continue on the dose received at the end of Stage 1, unless a dose change is required. Doses may be titrated for efficacy (to achieve age specific target Serum phosphorus levels), provided a subject has been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time during Stage 2.
Sponsors
Vifor Fresenius Medical Care Renal Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects 0 to \<18 years at time of consent. 2. Subjects with hyperphosphataemia 3. Subjects ≥1 year with CKD Stages 4-5 defined by a glomerular filtration rate \<30 mL/min/1.73 m2 or with CKD Stage 5D receiving adequate maintenance haemodialysis (HD) or peritoneal dialysis (PD) for at least 2 months prior to screening. 4. Subjects \<1 year must have CKD. 5. Appropriate written informed consent and, where appropriate/required assent, have been provided.
Exclusion criteria
1. Subjects with hypercalcaemia at screening 2. Subjects with intact parathyroid hormone (iPTH) levels \>700 pg/mL at screening. 3. Subjects who are PB naïve who weigh \<5 kg at screening. Subjects receiving stable doses of PBs who weigh \<6 kg at screening 4. Subjects requiring feeding tube sizes ≤6 FR (French catheter scale). 5. Subjects with history of major gastrointestinal surgery or significant gastrointestinal disorders. 6. Subjects with hypocalcaemia (serum total corrected calcium \<1.9 mmol/L; \<7.6 mg/dL) at screening. 7. Subject is pregnant (e.g., positive human chorionic gonadotropin test) or breast feeding. 8. Subject has a significant medical condition(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the PA21 Group | From Baseline to the End of Stage 1 (up to 10 weeks after treatment start date) | — |
| Number and Percentage of Participants Who Withdrew Due to Treatment Emergent Adverse Events | through study completion, up to 34 weeks after treatment start date | Any adverse event Leading to Study Drug Withdrawal is considered. |
| Number and Percentage of Participants With Any Treatment Emergent Adverse Event | through study completion, up to 34 weeks after treatment start date | Please note that in this section we are presenting just the overview of the adverse events experienced by the trial participants, in particular, the number of participants with at least one TEAEs until end of stage 2. Please refer to the detailed tables included on the Adverse Event Module for specifics. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | through study completion, up to 34 weeks after treatment start date | Number and percentages of participants with serum phosphorus levels below, within and above age-dependent normal ranges at baseline, at the end of Stage 1 and at the end of Stage 2. The age related normal ranges for serum phosphorus levels are: * 0 to \<1year 1.36 - 2.62 mmol/L * 1 year to \<6 years 1.03 - 1.97 mmol/L * 6 years to \<9 years 1.03 - 1.97 mmol/L * 9 years to \<10 years 1.03 - 1.97 mmol/L * 10 years to \<15 years 1.00 - 1.94 mmol/L * 15 years to ≤18 years 0.71 - 1.65 mmol/L |
| Serum Phosphorus Values at Each Visit | through study completion, up to 34 weeks after treatment start date | — |
| Serum Total Corrected Calcium at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Participants With Sustained Hypercalcaemia | through study completion, up to 34 weeks after treatment start date | Number and percentages of participants with at least 1 episode of sustained hypercalcaemia (defined as total calcium value above the upper safety limit confirmed by repeat sample 1 week later) during the study |
| Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | Summary statistics of Serum total corrected calcium-phosphorus product at each time point and change from baseline, where serum total corrected calcium-phosphorus product correspond to the product of serum total calcium and Phosphorus, expressed in mmol\^2/L\^2 |
| Serum iPTH Levels at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Ferritin Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the Phoslyra Group | From Baseline to the End of Stage 1 (up to 10 weeks after treatment start date) | — |
| Transferrin Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Osteocalcin-CL Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Iron Values at Each Time Point and Change From Baseline | From baseline through study completion, up to 34 weeks after treatment start date | — |
| Change in Serum Phosphorus Level From Baseline to the End of Stage 2 in Both Groups | From baseline to study completion, up to 34 weeks after treatment start date | — |
| Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | through study completion, up to 34 weeks after treatment start date | Number and percentages of participants with serum phosphorus levels below, within and above age-dependent target ranges at baseline, at the end of Stage 1 and at the end of Stage 2. The age target ranges for serum phosphorus levels are: * 0 to \<1 year 1.62-2.52 mmol/L * 1 year to \<6 years 1.45-2.10 mmol/L * 6 years to \<13 years 1.16-1.87 mmol/L * 13 years to ≤18 years 0.74-1.45 mmol/L |
Countries
France, Germany, Lithuania, Poland, Romania, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PA21 (Velphoro®) Formulations:
PA21 (Velphoro®), chewable tablets 500 mg and 250 mg iron
PA21 (Velphoro®), powder for oral suspension 500 mg, 250 mg and 125 mg iron
Stage 1 (Open-Label Dose Titration; up to 10 weeks): starting dose based on the participant's age. Dose was increased or decreased as required for efficacy (to achieve age specific target serum phosphorus level), provided a subject had been receiving that dose for a minimum of 2 weeks, and for safety/tolerability reasons at any time.
Stage 2 (Open-Label Safety Extension, 24 week safety extension): dose received at the end of Stage 1, unless a dose change is required. Doses could be titrated for efficacy (to achieve age specific target Serum phosphorus levels), provided a subject had been receiving that dose for a minimum of 2 weeks, and for safety or tolerability reasons at any time. | 66 |
| Calcium Acetate (Phoslyra®) Formulation:
Calcium Acetate (Phoslyra®) - Oral Solution: 667 mg calcium acetate per 5 mL.
Stage 1 (Open-Label Dose Titration; up to 10 weeks): starting dose based on the participant's weight or, if considered more appropriate by the Investigator, at an equivalent dose of their previous phosphate binder (PB), calcium-based or sevelamer. Dose was increased or decreased as required for efficacy (to achieve age specific target serum phosphorus level), provided a subject had been receiving that dose for a minimum of 2 weeks, and for safety/tolerability reasons at any time.
Stage 2 (Open-Label Safety Extension, 24 week safety extension): dose received at the end of Stage 1, unless a dose change is required. Doses could be titrated for efficacy (to achieve age specific target Serum phosphorus levels), provided a subject had been receiving that dose for a minimum of 2 weeks, and for safety/tolerability reasons at any time. | 19 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | AE/Kidney transplant | 1 | 0 |
| Overall Study | AE/Lack of efficacy | 1 | 0 |
| Overall Study | AE/Non-compl. | 1 | 0 |
| Overall Study | AE/Non-compl./Withd. parent | 0 | 1 |
| Overall Study | AE/Other | 0 | 1 |
| Overall Study | AE/Physician decision | 1 | 0 |
| Overall Study | AE/Withd. parent | 3 | 0 |
| Overall Study | AE/Withd. parent/Withd. subject | 1 | 1 |
| Overall Study | AE/Withd. subject | 1 | 0 |
| Overall Study | Kidney transplant | 10 | 4 |
| Overall Study | Lack of Efficacy | 3 | 2 |
| Overall Study | Lack of efficacy/Physician decision | 0 | 1 |
| Overall Study | Non-compliance with study drug | 4 | 0 |
| Overall Study | Non-compl./Ph. decision/Withd. subject | 1 | 1 |
| Overall Study | Non-compl./Physician decision | 2 | 0 |
| Overall Study | Non-compl./Withd. subject | 0 | 2 |
| Overall Study | Phosphorus >7 mg/dL - Withd. by sponsor | 1 | 0 |
| Overall Study | Phosphorus level outside safe range | 0 | 1 |
| Overall Study | Study drug taste/Withd. parent | 1 | 0 |
| Overall Study | Subject moving out | 2 | 0 |
| Overall Study | Subject taken off dialysis | 1 | 0 |
| Overall Study | Withdrawal by parent | 3 | 0 |
Baseline characteristics
| Characteristic | PA21 (Velphoro®) | Total | Calcium Acetate (Phoslyra®) |
|---|---|---|---|
| Age, Continuous | 12.2 years STANDARD_DEVIATION 4.07 | 12.3 years STANDARD_DEVIATION 3.98 | 12.6 years STANDARD_DEVIATION 3.73 |
| Age, Customized Age, Categorical Adolescents (12-17 years) | 42 Participants | 55 Participants | 13 Participants |
| Age, Customized Age, Categorical Adults (18-64 years) | 1 Participants | 1 Participants | 0 Participants |
| Age, Customized Age, Categorical Children (2-11 years) | 23 Participants | 29 Participants | 6 Participants |
| Age, Customized Age, Categorical Infants (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Age, Categorical Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants |
| Body Mass Index | 19.621 kg/m^2 STANDARD_DEVIATION 4.6182 | 19.366 kg/m^2 STANDARD_DEVIATION 4.5743 | 18.483 kg/m^2 STANDARD_DEVIATION 4.4238 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 25 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 60 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height | 142.3 cm STANDARD_DEVIATION 24.1 | 141.9 cm STANDARD_DEVIATION 23.98 | 140.3 cm STANDARD_DEVIATION 24.12 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 11 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 14 Participants | 2 Participants |
| Race (NIH/OMB) White | 43 Participants | 57 Participants | 14 Participants |
| Region of Enrollment France | 6 participants | 6 participants | 0 participants |
| Region of Enrollment Germany | 5 participants | 6 participants | 1 participants |
| Region of Enrollment Lithuania | 3 participants | 3 participants | 0 participants |
| Region of Enrollment Poland | 4 participants | 6 participants | 2 participants |
| Region of Enrollment Romania | 8 participants | 9 participants | 1 participants |
| Region of Enrollment Russia | 1 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 39 participants | 53 participants | 14 participants |
| Sex: Female, Male Female | 34 Participants | 47 Participants | 13 Participants |
| Sex: Female, Male Male | 32 Participants | 38 Participants | 6 Participants |
| Weight | 41.90 kg STANDARD_DEVIATION 18.023 | 41.10 kg STANDARD_DEVIATION 17.939 | 38.28 kg STANDARD_DEVIATION 17.834 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 19 |
| other Total, other adverse events | 45 / 66 | 14 / 19 |
| serious Total, serious adverse events | 18 / 66 | 3 / 19 |
Outcome results
Primary
Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the PA21 Group
Time frame: From Baseline to the End of Stage 1 (up to 10 weeks after treatment start date)
Population: Full Analysis Set (FAS) Population: all participants randomised to treatment at Stage 1 who received at least 1 dose of randomised treatment and who had at least 1 post-baseline assessment of the efficacy endpoint (serum phosphorus level), analysed according to treatment randomised.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PA21 (Velphoro®) | Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the PA21 Group | -0.120 mmol/L | Standard Error 0.081 |
Comparison: Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 1 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effects.p-value: 0.1465t-test, 2 sided
Primary
Number and Percentage of Participants Who Withdrew Due to Treatment Emergent Adverse Events
Any adverse event Leading to Study Drug Withdrawal is considered.
Time frame: through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PA21 (Velphoro®) | Number and Percentage of Participants Who Withdrew Due to Treatment Emergent Adverse Events | 12 Participants |
| Calcium Acetate (Phoslyra®) | Number and Percentage of Participants Who Withdrew Due to Treatment Emergent Adverse Events | 6 Participants |
Primary
Number and Percentage of Participants With Any Treatment Emergent Adverse Event
Please note that in this section we are presenting just the overview of the adverse events experienced by the trial participants, in particular, the number of participants with at least one TEAEs until end of stage 2. Please refer to the detailed tables included on the Adverse Event Module for specifics.
Time frame: through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PA21 (Velphoro®) | Number and Percentage of Participants With Any Treatment Emergent Adverse Event | 50 Participants |
| Calcium Acetate (Phoslyra®) | Number and Percentage of Participants With Any Treatment Emergent Adverse Event | 14 Participants |
Secondary
25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 79.8 nmol/L | Standard Deviation 34.25 |
| PA21 (Velphoro®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -4.1 nmol/L | Standard Deviation 24.28 |
| PA21 (Velphoro®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 76.0 nmol/L | Standard Deviation 37.48 |
| PA21 (Velphoro®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -18.3 nmol/L | Standard Deviation 27.77 |
| PA21 (Velphoro®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | Baseline | 83.1 nmol/L | Standard Deviation 38.74 |
| Calcium Acetate (Phoslyra®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -21.8 nmol/L | Standard Deviation 15.28 |
| Calcium Acetate (Phoslyra®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | Baseline | 81.7 nmol/L | Standard Deviation 40.32 |
| Calcium Acetate (Phoslyra®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 74.4 nmol/L | Standard Deviation 38.68 |
| Calcium Acetate (Phoslyra®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 59.0 nmol/L | Standard Deviation 17.18 |
| Calcium Acetate (Phoslyra®) | 25-Hydroxy Vitamin D Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -9.7 nmol/L | Standard Deviation 22.68 |
Secondary
Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 50.37 ug/L | Standard Deviation 42.382 |
| PA21 (Velphoro®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 7.29 ug/L | Standard Deviation 28.837 |
| PA21 (Velphoro®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 55.31 ug/L | Standard Deviation 43.363 |
| PA21 (Velphoro®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 7.74 ug/L | Standard Deviation 41.156 |
| PA21 (Velphoro®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | Baseline | 47.77 ug/L | Standard Deviation 35.469 |
| Calcium Acetate (Phoslyra®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -4.18 ug/L | Standard Deviation 38.713 |
| Calcium Acetate (Phoslyra®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | Baseline | 55.55 ug/L | Standard Deviation 50.249 |
| Calcium Acetate (Phoslyra®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 56.15 ug/L | Standard Deviation 64.537 |
| Calcium Acetate (Phoslyra®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 71.46 ug/L | Standard Deviation 64.427 |
| Calcium Acetate (Phoslyra®) | Bone Specific Alkaline Phosphatase Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 2.38 ug/L | Standard Deviation 27.375 |
Secondary
Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the Phoslyra Group
Time frame: From Baseline to the End of Stage 1 (up to 10 weeks after treatment start date)
Population: Full Analysis Set (FAS) Population: all participants randomised to treatment at Stage 1 who received at least 1 dose of randomised treatment and who had at least 1 post-baseline assessment of the efficacy endpoint (serum phosphorus level), analysed according to treatment randomised.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PA21 (Velphoro®) | Change in Serum Phosphorus Level From Baseline to the End of Stage 1 in the Phoslyra Group | -0.615 mmol/L | Standard Error 0.32 |
Comparison: Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 1 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effectsp-value: 0.0872t-test, 2 sided
Secondary
Change in Serum Phosphorus Level From Baseline to the End of Stage 2 in Both Groups
Time frame: From baseline to study completion, up to 34 weeks after treatment start date
Population: Full Analysis Set (FAS) Population: all participants randomised to treatment at Stage 1 who received at least 1 dose of randomised treatment and who had at least 1 post-baseline assessment of the efficacy endpoint (serum phosphorus level), analysed according to treatment randomised.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PA21 (Velphoro®) | Change in Serum Phosphorus Level From Baseline to the End of Stage 2 in Both Groups | 0.099 mmol/L | Standard Error 0.198 |
| Calcium Acetate (Phoslyra®) | Change in Serum Phosphorus Level From Baseline to the End of Stage 2 in Both Groups | -0.393 mmol/L | Standard Error 0.218 |
Comparison: Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 2 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effects.p-value: 0.6207t-test, 2 sided
Comparison: Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 2 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effects.p-value: 0.3226t-test, 2 sided
Secondary
Ferritin Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Ferritin Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 322.59 ug/L | Standard Deviation 368.823 |
| PA21 (Velphoro®) | Ferritin Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 48.59 ug/L | Standard Deviation 168.999 |
| PA21 (Velphoro®) | Ferritin Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 326.13 ug/L | Standard Deviation 304.864 |
| PA21 (Velphoro®) | Ferritin Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 137.57 ug/L | Standard Deviation 149.176 |
| PA21 (Velphoro®) | Ferritin Values at Each Time Point and Change From Baseline | Baseline | 223.67 ug/L | Standard Deviation 274.071 |
| Calcium Acetate (Phoslyra®) | Ferritin Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 110.69 ug/L | Standard Deviation 211.054 |
| Calcium Acetate (Phoslyra®) | Ferritin Values at Each Time Point and Change From Baseline | Baseline | 234.28 ug/L | Standard Deviation 228.825 |
| Calcium Acetate (Phoslyra®) | Ferritin Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 310.46 ug/L | Standard Deviation 369.869 |
| Calcium Acetate (Phoslyra®) | Ferritin Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 345.13 ug/L | Standard Deviation 366.23 |
| Calcium Acetate (Phoslyra®) | Ferritin Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 59.27 ug/L | Standard Deviation 219.66 |
Secondary
Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 775.7 pg/mL | Standard Deviation 514.86 |
| PA21 (Velphoro®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -60.7 pg/mL | Standard Deviation 454.95 |
| PA21 (Velphoro®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 603.5 pg/mL | Standard Deviation 531.86 |
| PA21 (Velphoro®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -187.6 pg/mL | Standard Deviation 507.26 |
| PA21 (Velphoro®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | Baseline | 820.1 pg/mL | Standard Deviation 503.9 |
| Calcium Acetate (Phoslyra®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 47.8 pg/mL | Standard Deviation 467.87 |
| Calcium Acetate (Phoslyra®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | Baseline | 814.9 pg/mL | Standard Deviation 468.89 |
| Calcium Acetate (Phoslyra®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 767.7 pg/mL | Standard Deviation 482.47 |
| Calcium Acetate (Phoslyra®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 747.4 pg/mL | Standard Deviation 628.27 |
| Calcium Acetate (Phoslyra®) | Fibroblast Growth Factor 23 Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -41.8 pg/mL | Standard Deviation 729.27 |
Secondary
Iron Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Iron Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 14.70 umol/L | Standard Deviation 7.425 |
| PA21 (Velphoro®) | Iron Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 1.64 umol/L | Standard Deviation 8.946 |
| PA21 (Velphoro®) | Iron Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 14.31 umol/L | Standard Deviation 6.005 |
| PA21 (Velphoro®) | Iron Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 1.95 umol/L | Standard Deviation 6.94 |
| PA21 (Velphoro®) | Iron Values at Each Time Point and Change From Baseline | Baseline | 13.20 umol/L | Standard Deviation 6.948 |
| Calcium Acetate (Phoslyra®) | Iron Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 1.35 umol/L | Standard Deviation 9.691 |
| Calcium Acetate (Phoslyra®) | Iron Values at Each Time Point and Change From Baseline | Baseline | 15.25 umol/L | Standard Deviation 8.488 |
| Calcium Acetate (Phoslyra®) | Iron Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 12.66 umol/L | Standard Deviation 4.821 |
| Calcium Acetate (Phoslyra®) | Iron Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 13.08 umol/L | Standard Deviation 4.967 |
| Calcium Acetate (Phoslyra®) | Iron Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.18 umol/L | Standard Deviation 7.197 |
Secondary
Osteocalcin-CL Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 586.0 ug/L | Standard Deviation 421.72 |
| PA21 (Velphoro®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 28.4 ug/L | Standard Deviation 248.44 |
| PA21 (Velphoro®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 516.9 ug/L | Standard Deviation 429.24 |
| PA21 (Velphoro®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 20.3 ug/L | Standard Deviation 342.77 |
| PA21 (Velphoro®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | Baseline | 517.9 ug/L | Standard Deviation 357.11 |
| Calcium Acetate (Phoslyra®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -91.0 ug/L | Standard Deviation 200.09 |
| Calcium Acetate (Phoslyra®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | Baseline | 681.5 ug/L | Standard Deviation 445.94 |
| Calcium Acetate (Phoslyra®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 753.1 ug/L | Standard Deviation 412.38 |
| Calcium Acetate (Phoslyra®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 709.0 ug/L | Standard Deviation 462.59 |
| Calcium Acetate (Phoslyra®) | Osteocalcin-CL Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 20.0 ug/L | Standard Deviation 179.26 |
Secondary
Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage
Number and percentages of participants with serum phosphorus levels below, within and above age-dependent target ranges at baseline, at the end of Stage 1 and at the end of Stage 2. The age target ranges for serum phosphorus levels are: * 0 to \<1 year 1.62-2.52 mmol/L * 1 year to \<6 years 1.45-2.10 mmol/L * 6 years to \<13 years 1.16-1.87 mmol/L * 13 years to ≤18 years 0.74-1.45 mmol/L
Time frame: through study completion, up to 34 weeks after treatment start date
Population: Full Analysis Set (FAS) Population: all participants randomised to treatment at Stage 1 who received at least 1 dose of randomised treatment and who had at least 1 post-baseline assessment of the efficacy endpoint (serum phosphorus level), analysed according to treatment randomised.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | Baseline | Within | 11 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 1 | Above | 37 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 1 | Below | 2 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 2 | Below | 1 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | Baseline | Above | 52 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 2 | Within | 14 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 1 | Within | 25 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 2 | Above | 25 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | Baseline | Below | 2 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 2 | Above | 6 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | Baseline | Below | 1 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | Baseline | Within | 1 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | Baseline | Above | 13 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 1 | Below | 1 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 1 | Within | 2 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 1 | Above | 12 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 2 | Below | 0 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage | End of Stage 2 | Within | 2 Participants |
Secondary
Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage
Number and percentages of participants with serum phosphorus levels below, within and above age-dependent normal ranges at baseline, at the end of Stage 1 and at the end of Stage 2. The age related normal ranges for serum phosphorus levels are: * 0 to \<1year 1.36 - 2.62 mmol/L * 1 year to \<6 years 1.03 - 1.97 mmol/L * 6 years to \<9 years 1.03 - 1.97 mmol/L * 9 years to \<10 years 1.03 - 1.97 mmol/L * 10 years to \<15 years 1.00 - 1.94 mmol/L * 15 years to ≤18 years 0.71 - 1.65 mmol/L
Time frame: through study completion, up to 34 weeks after treatment start date
Population: Full Analysis Set (FAS) Population: all participants randomised to treatment at Stage 1 who received at least 1 dose of randomised treatment and who had at least 1 post-baseline assessment of the efficacy endpoint (serum phosphorus level), analysed according to treatment randomised.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | Baseline | Within | 24 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 1 | Above | 24 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 1 | Below | 1 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 2 | Below | 1 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | Baseline | Above | 40 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 2 | Within | 23 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 1 | Within | 39 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 2 | Above | 16 Participants |
| PA21 (Velphoro®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | Baseline | Below | 1 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 2 | Above | 6 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | Baseline | Below | 1 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | Baseline | Within | 5 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | Baseline | Above | 9 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 1 | Below | 1 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 1 | Within | 6 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 1 | Above | 8 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 2 | Below | 0 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage | End of Stage 2 | Within | 2 Participants |
Secondary
Participants With Sustained Hypercalcaemia
Number and percentages of participants with at least 1 episode of sustained hypercalcaemia (defined as total calcium value above the upper safety limit confirmed by repeat sample 1 week later) during the study
Time frame: through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PA21 (Velphoro®) | Participants With Sustained Hypercalcaemia | 6 Participants |
| Calcium Acetate (Phoslyra®) | Participants With Sustained Hypercalcaemia | 4 Participants |
Secondary
Serum iPTH Levels at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Serum iPTH Levels at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 28.28 pmol/L | Standard Deviation 20.972 |
| PA21 (Velphoro®) | Serum iPTH Levels at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -2.49 pmol/L | Standard Deviation 22.139 |
| PA21 (Velphoro®) | Serum iPTH Levels at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 35.60 pmol/L | Standard Deviation 32.903 |
| PA21 (Velphoro®) | Serum iPTH Levels at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 4.61 pmol/L | Standard Deviation 38.858 |
| PA21 (Velphoro®) | Serum iPTH Levels at Each Time Point and Change From Baseline | Baseline | 30.36 pmol/L | Standard Deviation 26.393 |
| Calcium Acetate (Phoslyra®) | Serum iPTH Levels at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 12.01 pmol/L | Standard Deviation 27.151 |
| Calcium Acetate (Phoslyra®) | Serum iPTH Levels at Each Time Point and Change From Baseline | Baseline | 37.12 pmol/L | Standard Deviation 19.527 |
| Calcium Acetate (Phoslyra®) | Serum iPTH Levels at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 45.90 pmol/L | Standard Deviation 28.363 |
| Calcium Acetate (Phoslyra®) | Serum iPTH Levels at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 52.30 pmol/L | Standard Deviation 36.143 |
| Calcium Acetate (Phoslyra®) | Serum iPTH Levels at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 5.72 pmol/L | Standard Deviation 20.166 |
Secondary
Serum Phosphorus Values at Each Visit
Time frame: through study completion, up to 34 weeks after treatment start date
Population: Full Analysis Set (FAS) Population: all participants randomised to treatment at Stage 1 who received at least 1 dose of randomised treatment and who had at least 1 post-baseline assessment of the efficacy endpoint (serum phosphorus level), analysed according to treatment randomised.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Serum Phosphorus Values at Each Visit | Baseline | 2.07 mmol/L | Standard Deviation 0.522 |
| PA21 (Velphoro®) | Serum Phosphorus Values at Each Visit | End of Stage 1 | 1.82 mmol/L | Standard Deviation 0.575 |
| PA21 (Velphoro®) | Serum Phosphorus Values at Each Visit | End of Stage 2 | 1.71 mmol/L | Standard Deviation 0.506 |
| Calcium Acetate (Phoslyra®) | Serum Phosphorus Values at Each Visit | Baseline | 2.15 mmol/L | Standard Deviation 0.669 |
| Calcium Acetate (Phoslyra®) | Serum Phosphorus Values at Each Visit | End of Stage 1 | 2.17 mmol/L | Standard Deviation 0.804 |
| Calcium Acetate (Phoslyra®) | Serum Phosphorus Values at Each Visit | End of Stage 2 | 2.09 mmol/L | Standard Deviation 0.594 |
Secondary
Serum Total Corrected Calcium at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 2.35 mmol/L | Standard Deviation 0.212 |
| PA21 (Velphoro®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.03 mmol/L | Standard Deviation 0.224 |
| PA21 (Velphoro®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 2.28 mmol/L | Standard Deviation 0.185 |
| PA21 (Velphoro®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.06 mmol/L | Standard Deviation 0.197 |
| PA21 (Velphoro®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | Baseline | 2.38 mmol/L | Standard Deviation 0.144 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.07 mmol/L | Standard Deviation 0.207 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | Baseline | 2.37 mmol/L | Standard Deviation 0.185 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 2.31 mmol/L | Standard Deviation 0.13 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 2.36 mmol/L | Standard Deviation 0.154 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.06 mmol/L | Standard Deviation 0.212 |
Secondary
Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline
Summary statistics of Serum total corrected calcium-phosphorus product at each time point and change from baseline, where serum total corrected calcium-phosphorus product correspond to the product of serum total calcium and Phosphorus, expressed in mmol\^2/L\^2
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 4.25 mmol^2/L^2 | Standard Deviation 1.392 |
| PA21 (Velphoro®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.65 mmol^2/L^2 | Standard Deviation 1.221 |
| PA21 (Velphoro®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 3.91 mmol^2/L^2 | Standard Deviation 1.211 |
| PA21 (Velphoro®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.49 mmol^2/L^2 | Standard Deviation 1.384 |
| PA21 (Velphoro®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | Baseline | 4.94 mmol^2/L^2 | Standard Deviation 1.4 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.12 mmol^2/L^2 | Standard Deviation 1.227 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | Baseline | 5.31 mmol^2/L^2 | Standard Deviation 1.831 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 5.05 mmol^2/L^2 | Standard Deviation 1.608 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 4.90 mmol^2/L^2 | Standard Deviation 1.289 |
| Calcium Acetate (Phoslyra®) | Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.31 mmol^2/L^2 | Standard Deviation 2.152 |
Secondary
Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 8.55 U/L | Standard Deviation 8.305 |
| PA21 (Velphoro®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | 0.02 U/L | Standard Deviation 2.746 |
| PA21 (Velphoro®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 8.25 U/L | Standard Deviation 5.643 |
| PA21 (Velphoro®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | 0.72 U/L | Standard Deviation 4.108 |
| PA21 (Velphoro®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | Baseline | 8.86 U/L | Standard Deviation 7.646 |
| Calcium Acetate (Phoslyra®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.16 U/L | Standard Deviation 2.422 |
| Calcium Acetate (Phoslyra®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | Baseline | 8.82 U/L | Standard Deviation 5.161 |
| Calcium Acetate (Phoslyra®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 8.82 U/L | Standard Deviation 5.16 |
| Calcium Acetate (Phoslyra®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 7.62 U/L | Standard Deviation 2.044 |
| Calcium Acetate (Phoslyra®) | Tartrate-resistant Acid Phosphatase 5b Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.11 U/L | Standard Deviation 4.58 |
Secondary
Transferrin Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Transferrin Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 1.96 g/L | Standard Deviation 0.52 |
| PA21 (Velphoro®) | Transferrin Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.17 g/L | Standard Deviation 0.342 |
| PA21 (Velphoro®) | Transferrin Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 1.89 g/L | Standard Deviation 0.513 |
| PA21 (Velphoro®) | Transferrin Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.28 g/L | Standard Deviation 0.506 |
| PA21 (Velphoro®) | Transferrin Values at Each Time Point and Change From Baseline | Baseline | 2.12 g/L | Standard Deviation 0.607 |
| Calcium Acetate (Phoslyra®) | Transferrin Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.12 g/L | Standard Deviation 0.289 |
| Calcium Acetate (Phoslyra®) | Transferrin Values at Each Time Point and Change From Baseline | Baseline | 1.99 g/L | Standard Deviation 0.565 |
| Calcium Acetate (Phoslyra®) | Transferrin Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 1.97 g/L | Standard Deviation 0.588 |
| Calcium Acetate (Phoslyra®) | Transferrin Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 1.98 g/L | Standard Deviation 0.439 |
| Calcium Acetate (Phoslyra®) | Transferrin Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.05 g/L | Standard Deviation 0.234 |
Secondary
Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 4.57 ug/L | Standard Deviation 1.549 |
| PA21 (Velphoro®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.45 ug/L | Standard Deviation 1.387 |
| PA21 (Velphoro®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 4.21 ug/L | Standard Deviation 1.591 |
| PA21 (Velphoro®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.42 ug/L | Standard Deviation 1.893 |
| PA21 (Velphoro®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | Baseline | 4.77 ug/L | Standard Deviation 1.201 |
| Calcium Acetate (Phoslyra®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -0.34 ug/L | Standard Deviation 0.97 |
| Calcium Acetate (Phoslyra®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | Baseline | 4.31 ug/L | Standard Deviation 1.549 |
| Calcium Acetate (Phoslyra®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 5.10 ug/L | Standard Deviation 1.799 |
| Calcium Acetate (Phoslyra®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 4.43 ug/L | Standard Deviation 1.565 |
| Calcium Acetate (Phoslyra®) | Type I Collagen C-Telopeptides Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.03 ug/L | Standard Deviation 1.217 |
Secondary
Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline
Time frame: From baseline through study completion, up to 34 weeks after treatment start date
Population: Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 25.37 umol/L | Standard Deviation 11.162 |
| PA21 (Velphoro®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -3.64 umol/L | Standard Deviation 9.284 |
| PA21 (Velphoro®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 25.53 umol/L | Standard Deviation 11.672 |
| PA21 (Velphoro®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -4.38 umol/L | Standard Deviation 12.454 |
| PA21 (Velphoro®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | Baseline | 28.68 umol/L | Standard Deviation 12.985 |
| Calcium Acetate (Phoslyra®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | End of Stage 2 - Change from baseline | -3.53 umol/L | Standard Deviation 11.779 |
| Calcium Acetate (Phoslyra®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | Baseline | 25.54 umol/L | Standard Deviation 14.153 |
| Calcium Acetate (Phoslyra®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | End of Stage 1 - Observed data | 27.28 umol/L | Standard Deviation 9.671 |
| Calcium Acetate (Phoslyra®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | End of Stage 2 - Observed data | 26.04 umol/L | Standard Deviation 11.088 |
| Calcium Acetate (Phoslyra®) | Unsaturated Iron Binding Capacity Values at Each Time Point and Change From Baseline | End of Stage 1 - Change from baseline | -0.81 umol/L | Standard Deviation 7.176 |
Post Hoc
Change in Serum Phosphorus Level From Baseline to End of Stage 1 in PA21 Group, by Age Group
Time frame: From Baseline to the End of Stage 1 (up to 10 weeks after treatment start date)
Population: Full Analysis Set (FAS) Population: all participants randomised to treatment at Stage 1 who received at least 1 dose of randomised treatment and who had at least 1 post-baseline assessment of the efficacy endpoint (serum phosphorus level), analysed according to treatment randomised.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Change in Serum Phosphorus Level From Baseline to End of Stage 1 in PA21 Group, by Age Group | >=2 years to <6 years | -0.078 mmol/L | Standard Error 0.123 |
| PA21 (Velphoro®) | Change in Serum Phosphorus Level From Baseline to End of Stage 1 in PA21 Group, by Age Group | >=6 years to <12 years | -0.200 mmol/L | Standard Error 0.158 |
| PA21 (Velphoro®) | Change in Serum Phosphorus Level From Baseline to End of Stage 1 in PA21 Group, by Age Group | >=12 years to <=18 years | -0.149 mmol/L | Standard Error 0.062 |
| Unknown | Change in Serum Phosphorus Level From Baseline to End of Stage 1 in PA21 Group, by Age Group | <2 years | — mmol/L | — |
Comparison: Age group of \>=2 years to \<6 years~Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 1 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effects.p-value: 0.5682t-test, 2 sided
Comparison: Age group of \>=6 years to \<12 years~Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 1 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effects.p-value: 0.2271t-test, 2 sided
Comparison: Age group of \>=12 years to \<=18 years~Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 1 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effects.p-value: 0.022t-test, 2 sided
Post Hoc
Change in Serum Phosphorus (SP) Level From Baseline to End of Stage 1 in PA21 Group, by Serum Phosphorus Level at Baseline
The levels of Serum Phosphorus considered at baseline are those above vs within/below Age Related Normal Range
Time frame: From Baseline to the End of Stage 1 (up to 10 weeks after treatment start date)
Population: Full Analysis Set (FAS) Population: all participants randomised to treatment at Stage 1 who received at least 1 dose of randomised treatment and who had at least 1 post-baseline assessment of the efficacy endpoint (serum phosphorus level), analysed according to treatment randomised.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| PA21 (Velphoro®) | Change in Serum Phosphorus (SP) Level From Baseline to End of Stage 1 in PA21 Group, by Serum Phosphorus Level at Baseline | SP above Age Related Normal Range | -0.282 mmol/L | Standard Error 0.096 |
| PA21 (Velphoro®) | Change in Serum Phosphorus (SP) Level From Baseline to End of Stage 1 in PA21 Group, by Serum Phosphorus Level at Baseline | SP below/within Related Normal Range | 0.082 mmol/L | Standard Error 0.146 |
Comparison: Group of SP at baseline above Age Related Normal Range~Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 1 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effects.p-value: 0.0058t-test, 2 sided
Comparison: Group of SP at baseline below or within Age Related Normal Range~Results are obtained from a linear mixed model which includes change in serum phosphorus levels from baseline to the end of Stage 1 as dependent variable and treatment, baseline serum phosphorus, age (in categories) at randomisation, region (Non-US/US) and gender as fixed effects.p-value: 0.5801t-test, 2 sided