A Study to Investigate the Safety and Efficacy of PA21 (Velphoro®) and Calcium Acetate (Phoslyra®) in Paediatric and Adolescent Chronic Kidney Disease (CKD) Patients With Hyperphosphataemia

• Sponsor: Vifor Fresenius Medical Care Renal Pharma (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02688764
• Collaborator: (none)
• Enrollment: 85
• Locations: 38
• Arms: 2
• Actual Duration (Months): 32.9
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Hyperphosphatemia	Drug: PA21 (Velphoro®); Drug: Calcium Acetate (Phoslyra®)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 85 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Randomised, Active-controlled, Parallel Group, Multicentre, Phase 3 Study to Investigate the Safety and Efficacy of PA21 (Velphoro®) and Calcium Acetate (Phoslyra®) in Paediatric and Adolescent CKD Patients With Hyperphosphataemia
• Actual Study Start Date: May 26, 2016
• Actual Primary Completion Date: Feb 21, 2019
• Actual Study Completion Date: Feb 21, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PA21 (Velphoro®) PA21 (Velphoro®), chewable tablets 500 mg iron PA21 (Velphoro®), chewable tablets 250 mg iron PA21 (Velphoro®), powder for oral suspension 500 mg iron PA21 (Velphoro®), powder for oral suspension 250 mg iron PA21 (Velphoro®), powder for oral suspension 125 mg iron	Drug: PA21 (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.; Other Names: sucroferric oxyhydroxide
Active Comparator: Calcium Acetate (Phoslyra®) Calcium Acetate (Phoslyra®) - Oral Solution: 667 mg calcium acetate per 5 mL.	Drug: Calcium 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.

Outcome Measures

Primary Outcome Measures

1. 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)]

2. 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.

3. 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 Outcome Measures

1. 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)]

2. 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]

3. 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

4. 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

5. Serum Phosphorus Values at Each Visit [through study completion, up to 34 weeks after treatment start date]

6. 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]

7. 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

8. 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

9. Serum iPTH Levels at Each Time Point and Change From Baseline [From baseline through study completion, up to 34 weeks after treatment start date]

10. Ferritin Values at Each Time Point and Change From Baseline [From baseline through study completion, up to 34 weeks after treatment start date]

11. 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]

12. Iron Values at Each Time Point and Change From Baseline [From baseline through study completion, up to 34 weeks after treatment start date]

13. Transferrin Values at Each Time Point and Change From Baseline [From baseline through study completion, up to 34 weeks after treatment start date]

14. 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]

15. 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]

16. 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]

17. 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]

18. Osteocalcin-CL Values at Each Time Point and Change From Baseline [From baseline through study completion, up to 34 weeks after treatment start date]

19. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 18 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham School of Medicine	Birmingham	Alabama	United States	35233
2	Children's National Medical Center	Washington	District of Columbia	United States	20010
3	University of Miami - Miller School of Medicine	Miami	Florida	United States	33136
4	Nicklaus Children's Hospital	Miami	Florida	United States	33155
5	Nemours Children's Clinic - Orlando	Orlando	Florida	United States	32827
6	Emory-Children's Center	Atlanta	Georgia	United States	30322-1014
7	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
8	University of Michigan Hospital	Ann Arbor	Michigan	United States	48109
9	Washington University School of Medicine in St. Louis	Saint Louis	Missouri	United States	63110
10	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601-1914
11	Saint Barnabas Medical Center	Livingston	New Jersey	United States	07039-5672
12	The University of New Mexico	Albuquerque	New Mexico	United States	87131-0001
13	Weill Cornell Medical College	New York	New York	United States	10021
14	Duke University Medical Center	Durham	North Carolina	United States	27710
15	University of Oklahoma Medical Center	Oklahoma City	Oklahoma	United States	73104
16	Oregon Health and Science University, Doernbecher Children's Hospital	Portland	Oregon	United States	97239
17	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
18	The University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
19	Texas Children's Hospital - Texas Children's Feigin Center	Houston	Texas	United States	77030
20	The University of Texas Medical School at Houston	Houston	Texas	United States	77030
21	Primary Children's Hospital	Salt Lake City	Utah	United States	84113
22	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226
23	Hôpital Jeanne de Flandre	Lille		France
24	Chu de Lyon - Hopital Femme Mere Enfant	Lyon		France
25	Service de Néphrologie et Endocrinologie pédiatriques	Montpellier cedex 5		France	34295
26	Universitätsklinikum Erlangen	Erlangen		Germany	91054
27	Universitätsklinikum Gießen und Marburg GmbH	Marburg		Germany	35043
28	Hospital Of Lithuanian University Of Health Sciences Kaunas Clinics	Kaunas		Lithuania	LT-50009
29	Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos	Vilnius		Lithuania	8406
30	Uniwersytecki Dziecięcy Szpital Kliniczny im. L. Zamenhofa w Białymstoku	Białystok		Poland	15-274
31	Uniwersyteckie Centrum Kliniczne	Gdansk		Poland	80-952
32	Uniwersytecki Szpital Dzieciecy w Krakowie - Prokocimiu	Krakow		Poland	30-663
33	Instytut "Pomnik - Centrum Zdrowia Dziecka"	Warszawa		Poland
34	Spitalul Clinic de Urgenţă pentru copii "Maria Sklodowska Curie"	Bucureşti	Bucharest	Romania	077120
35	Spitalul Clinic Fundeni Bucureşti	București	Bucharest	Romania	22322
36	Children's Republican Clinical Hospital	Kazan		Russian Federation
37	St. Vladimir Children's City Clinical Hospital	Moscow		Russian Federation
38	St. Petersburg GBUZ "Children's City Hospital No. 1"	Saint Petersburg		Russian Federation

Sponsors and Collaborators

• Vifor Fresenius Medical Care Renal Pharma

Investigators

• Principal Investigator: Larry A Greenbaum, MD; PhD, Children's Healthcare of Atlanta at Egleston

Study Documents (Full-Text)

• Study Protocol - Sep 22, 2015
• Statistical Analysis Plan - Mar 20, 2019

More Information

Publications

None provided.

• Responsible Party: Vifor Fresenius Medical Care Renal Pharma
• ClinicalTrials.gov Identifier: NCT02688764
• Other Study ID Numbers: PA-CL-PED-01
• First Posted: Feb 23, 2016
• Last Update Posted: Sep 10, 2019
• Last Verified: Aug 1, 2019

• Keywords provided by Vifor Fresenius Medical Care Renal Pharma: PA21; phosphate binder
• Additional relevant MeSH terms: Hyperphosphatemia; Calcium; Calcium acetate

Study Results

Participant Flow

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	66	19
Treated in Stage 1	66	19
Treated in Stage 2	43	8
COMPLETED	26	2
NOT COMPLETED	40	17

Baseline Characteristics

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	66	19	85
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	12.2 (4.07)	12.6 (3.73)	12.3 (3.98)
Age, Customized (Count of Participants)
Newborns (0-27 days)	0 0%	0 0%	0 0%
Infants (28 days-23 months)	0 0%	0 0%	0 0%
Children (2-11 years)	23 34.8%	6 31.6%	29 34.1%
Adolescents (12-17 years)	42 63.6%	13 68.4%	55 64.7%
Adults (18-64 years)	1 1.5%	0 0%	1 1.2%
Sex: Female, Male (Count of Participants)
Female	34 51.5%	13 68.4%	47 55.3%
Male	32 48.5%	6 31.6%	38 44.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	20 30.3%	5 26.3%	25 29.4%
Not Hispanic or Latino	46 69.7%	14 73.7%	60 70.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.5%	0 0%	1 1.2%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 1.5%	1 5.3%	2 2.4%
Black or African American	9 13.6%	2 10.5%	11 12.9%
White	43 65.2%	14 73.7%	57 67.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	12 18.2%	2 10.5%	14 16.5%
Region of Enrollment (participants) [Number]
United States	39 59.1%	14 73.7%	53 62.4%
France	6 9.1%	0 0%	6 7.1%
Lithuania	3 4.5%	0 0%	3 3.5%
Poland	4 6.1%	2 10.5%	6 7.1%
Germany	5 7.6%	1 5.3%	6 7.1%
Russia	1 1.5%	1 5.3%	2 2.4%
Romania	8 12.1%	1 5.3%	9 10.6%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	142.3 (24.10)	140.3 (24.12)	141.9 (23.98)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	41.90 (18.023)	38.28 (17.834)	41.10 (17.939)
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	19.621 (4.6182)	18.483 (4.4238)	19.366 (4.5743)

Outcome Measures

1. Primary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PA21 (Velphoro®)
Arm/Group Description	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.
Measure Participants	65
Least Squares Mean (Standard Error) [mmol/L]	-0.120 (0.081)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PA21 (Velphoro®)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1465
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Number and Percentage of Participants Who Withdrew Due to Treatment Emergent Adverse Events
Description	Any adverse event Leading to Study Drug Withdrawal is considered.
Time Frame	through study completion, up to 34 weeks after treatment start date

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Count of Participants [Participants]	12 18.2%	6 31.6%

3. Primary Outcome

Title	Number and Percentage of Participants With Any Treatment Emergent Adverse Event
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Count of Participants [Participants]	50 75.8%	14 73.7%

4. Secondary Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.
Measure Participants	15
Least Squares Mean (Standard Error) [mmol/L]	-0.615 (0.320)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PA21 (Velphoro®)
	Comments	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
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0872
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

5. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	36	6
Least Squares Mean (Standard Error) [mmol/L]	0.099 (0.198)	-0.393 (0.218)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PA21 (Velphoro®)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6207
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Calcium Acetate (Phoslyra®)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3226
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

6. Secondary Outcome

Title	Participants With Serum Phosphorus Levels Within the Age-dependent Target Range in Each Stage
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	65	15
Below	2 3%	1 5.3%
Within	11 16.7%	1 5.3%
Above	52 78.8%	13 68.4%
Below	2 3%	1 5.3%
Within	25 37.9%	2 10.5%
Above	37 56.1%	12 63.2%
Below	1 1.5%	0 0%
Within	14 21.2%	2 10.5%
Above	25 37.9%	6 31.6%

7. Secondary Outcome

Title	Participants With Serum Phosphorus Levels Within the Age Related Normal Range in Each Stage
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	65	15
Below	1 1.5%	1 5.3%
Within	24 36.4%	5 26.3%
Above	40 60.6%	9 47.4%
Below	1 1.5%	1 5.3%
Within	39 59.1%	6 31.6%
Above	24 36.4%	8 42.1%
Below	1 1.5%	0 0%
Within	23 34.8%	2 10.5%
Above	16 24.2%	6 31.6%

8. Secondary Outcome

Title	Serum Phosphorus Values at Each Visit
Time Frame	through study completion, up to 34 weeks after treatment start date

Outcome Measure Data

Analysis Population Description

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/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	65	15
Baseline	2.07 (0.522)	2.15 (0.669)
End of Stage 1	1.82 (0.575)	2.17 (0.804)
End of Stage 2	1.71 (0.506)	2.09 (0.594)

9. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	2.38 (0.144)	2.37 (0.185)
End of Stage 1 - Observed data	2.35 (0.212)	2.31 (0.130)
End of Stage 2 - Observed data	2.28 (0.185)	2.36 (0.154)
End of Stage 1 - Change from baseline	-0.03 (0.224)	-0.06 (0.212)
End of Stage 2 - Change from baseline	-0.06 (0.197)	-0.07 (0.207)

10. Secondary Outcome

Title	Participants With Sustained Hypercalcaemia
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Count of Participants [Participants]	6 9.1%	4 21.1%

11. Secondary Outcome

Title	Serum Total Corrected Calcium-Phosphorus Product at Each Time Point and Change From Baseline
Description	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	4.94 (1.400)	5.31 (1.831)
End of Stage 1 - Observed data	4.25 (1.392)	5.05 (1.608)
End of Stage 2 - Observed data	3.91 (1.211)	4.90 (1.289)
End of Stage 1 - Change from baseline	-0.65 (1.221)	-0.31 (2.152)
End of Stage 2 - Change from baseline	-0.49 (1.384)	-0.12 (1.227)

12. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	30.36 (26.393)	37.12 (19.527)
End of Stage 1 - Observed data	28.28 (20.972)	45.90 (28.363)
End of Stage 2 - Observed data	35.60 (32.903)	52.30 (36.143)
End of Stage 1 - Change from baseline	-2.49 (22.139)	5.72 (20.166)
End of Stage 2 - Change from baseline	4.61 (38.858)	12.01 (27.151)

13. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	223.67 (274.071)	234.28 (228.825)
End of Stage 1 - Observed data	322.59 (368.823)	310.46 (369.869)
End of Stage 2 - Observed data	326.13 (304.864)	345.13 (366.230)
End of Stage 1 - Change from baseline	48.59 (168.999)	59.27 (219.660)
End of Stage 2 - Change from baseline	137.57 (149.176)	110.69 (211.054)

14. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	28.68 (12.985)	25.54 (14.153)
End of Stage 1 - Observed data	25.37 (11.162)	27.28 (9.671)
End of Stage 2 - Observed data	25.53 (11.672)	26.04 (11.088)
End of Stage 1 - Change from baseline	-3.64 (9.284)	-0.81 (7.176)
End of Stage 2 - Change from baseline	-4.38 (12.454)	-3.53 (11.779)

15. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	13.20 (6.948)	15.25 (8.488)
End of Stage 1 - Observed data	14.70 (7.425)	12.66 (4.821)
End of Stage 2 - Observed data	14.31 (6.005)	13.08 (4.967)
End of Stage 1 - Change from baseline	1.64 (8.946)	-0.18 (7.197)
End of Stage 2 - Change from baseline	1.95 (6.940)	1.35 (9.691)

16. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	2.12 (0.607)	1.99 (0.565)
End of Stage 1 - Observed data	1.96 (0.520)	1.97 (0.588)
End of Stage 2 - Observed data	1.89 (0.513)	1.98 (0.439)
End of Stage 1 - Change from baseline	-0.17 (0.342)	-0.05 (0.234)
End of Stage 2 - Change from baseline	-0.28 (0.506)	-0.12 (0.289)

17. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	83.1 (38.74)	81.7 (40.32)
End of Stage 1 - Observed data	79.8 (34.25)	74.4 (38.68)
End of Stage 2 - Observed data	76.0 (37.48)	59.0 (17.18)
End of Stage 1 - Change from baseline	-4.1 (24.28)	-9.7 (22.68)
End of Stage 2 - Change from baseline	-18.3 (27.77)	-21.8 (15.28)

18. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	47.77 (35.469)	55.55 (50.249)
End of Stage 1 - Observed data	50.37 (42.382)	56.15 (64.537)
End of Stage 2 - Observed data	55.31 (43.363)	71.46 (64.427)
End of Stage 1 - Change from baseline	7.29 (28.837)	2.38 (27.375)
End of Stage 2 - Change from baseline	7.74 (41.156)	-4.18 (38.713)

19. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	4.77 (1.201)	4.31 (1.549)
End of Stage 1 - Observed data	4.57 (1.549)	5.10 (1.799)
End of Stage 2 - Observed data	4.21 (1.591)	4.43 (1.565)
End of Stage 1 - Change from baseline	-0.45 (1.387)	-0.03 (1.217)
End of Stage 2 - Change from baseline	-0.42 (1.893)	-0.34 (0.970)

20. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	820.1 (503.90)	814.9 (468.89)
End of Stage 1 - Observed data	775.7 (514.86)	767.7 (482.47)
End of Stage 2 - Observed data	603.5 (531.86)	747.4 (628.27)
End of Stage 1 - Change from baseline	-60.7 (454.95)	-41.8 (729.27)
End of Stage 2 - Change from baseline	-187.6 (507.26)	47.8 (467.87)

21. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	517.9 (357.11)	681.5 (445.94)
End of Stage 1 - Observed data	586.0 (421.72)	753.1 (412.38)
End of Stage 2 - Observed data	516.9 (429.24)	709.0 (462.59)
End of Stage 1 - Change from baseline	28.4 (248.44)	20.0 (179.26)
End of Stage 2 - Change from baseline	20.3 (342.77)	-91.0 (200.09)

22. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Safety Population: all participants who received at least 1 dose of study medication, analysed according to treatment received.

Arm/Group Title	PA21 (Velphoro®)	Calcium Acetate (Phoslyra®)
Arm/Group Description	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.	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.
Measure Participants	66	19
Baseline	8.86 (7.646)	8.82 (5.161)
End of Stage 1 - Observed data	8.55 (8.305)	8.82 (5.160)
End of Stage 2 - Observed data	8.25 (5.643)	7.62 (2.044)
End of Stage 1 - Change from baseline	0.02 (2.746)	-0.11 (4.580)
End of Stage 2 - Change from baseline	0.72 (4.108)	-0.16 (2.422)

23. Post-Hoc Outcome

Title	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PA21 (Velphoro®)
Arm/Group Description	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.
Measure Participants	65
>=2 years to <6 years	-0.078 (0.123)
>=6 years to <12 years	-0.200 (0.158)
>=12 years to <=18 years	-0.149 (0.062)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PA21 (Velphoro®)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5682
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PA21 (Velphoro®)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2271
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PA21 (Velphoro®)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0220
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

24. Post-Hoc Outcome

Title	Change in Serum Phosphorus (SP) Level From Baseline to End of Stage 1 in PA21 Group, by Serum Phosphorus Level at Baseline
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	PA21 (Velphoro®)
Arm/Group Description	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.
Measure Participants	65
SP above Age Related Normal Range	-0.282 (0.096)
SP below/within Related Normal Range	0.082 (0.146)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PA21 (Velphoro®)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0058
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PA21 (Velphoro®)
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5801
	Comments	0.05 level of significance
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Through study completion, up to 34 weeks after treatment start date
Adverse Event Reporting Description	TEAEs (treatment emergent adverse events) are included in this section.
Arm/Group Title	PA21 (Velphoro®)		Calcium Acetate (Phoslyra®)
Arm/Group Description	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.		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.
All Cause Mortality
	PA21 (Velphoro®)		Calcium Acetate (Phoslyra®)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/66 (0%)		0/19 (0%)
Serious Adverse Events
	PA21 (Velphoro®)		Calcium Acetate (Phoslyra®)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/66 (27.3%)		3/19 (15.8%)
Cardiac disorders
Bradycardia	1/66 (1.5%)	1	0/19 (0%)	0
Cardiac tamponade	1/66 (1.5%)	1	0/19 (0%)	0
Eye disorders
Papilloedema	1/66 (1.5%)	1	0/19 (0%)	0
Gastrointestinal disorders
Gastritis	1/66 (1.5%)	1	0/19 (0%)	0
Ileus	1/66 (1.5%)	1	0/19 (0%)	0
Small intestinal obstruction	1/66 (1.5%)	1	0/19 (0%)	0
Small intestinal perforation	0/66 (0%)	0	1/19 (5.3%)	1
Vomiting	0/66 (0%)	0	1/19 (5.3%)	1
General disorders
Catheter site haematoma	1/66 (1.5%)	1	0/19 (0%)	0
Oedema peripheral	1/66 (1.5%)	1	0/19 (0%)	0
Puncture site reaction	1/66 (1.5%)	1	0/19 (0%)	0
Pyrexia	0/66 (0%)	0	1/19 (5.3%)	1
Infections and infestations
Device related sepsis	1/66 (1.5%)	1	0/19 (0%)	0
Sepsis	1/66 (1.5%)	2	0/19 (0%)	0
Superinfection	1/66 (1.5%)	1	0/19 (0%)	0
Tonsillitis streptococcal	1/66 (1.5%)	1	0/19 (0%)	0
Injury, poisoning and procedural complications
Arteriovenous fistula site complication	1/66 (1.5%)	1	0/19 (0%)	0
Arteriovenous fistula site haematoma	1/66 (1.5%)	1	0/19 (0%)	0
Arteriovenous fistula thrombosis	1/66 (1.5%)	1	0/19 (0%)	0
Investigations
Weight increased	2/66 (3%)	2	0/19 (0%)	0
Blood creatinine increased	1/66 (1.5%)	1	0/19 (0%)	0
Blood pressure increased	1/66 (1.5%)	1	0/19 (0%)	0
Glomerular filtration rate decreased	1/66 (1.5%)	1	0/19 (0%)	0
Weight decreased	0/66 (0%)	0	1/19 (5.3%)	1
Metabolism and nutrition disorders
Fluid overload	2/66 (3%)	2	0/19 (0%)	0
Decreased appetite	1/66 (1.5%)	1	0/19 (0%)	0
Dehydration	0/66 (0%)	0	1/19 (5.3%)	1
Electrolyte imbalance	0/66 (0%)	0	1/19 (5.3%)	1
Nervous system disorders
Benign intracranial hypertension	1/66 (1.5%)	1	0/19 (0%)	0
Product Issues
Device malfunction	2/66 (3%)	3	0/19 (0%)	0
Device extrusion	1/66 (1.5%)	1	0/19 (0%)	0
Device occlusion	0/66 (0%)	0	1/19 (5.3%)	2
Renal and urinary disorders
Azotaemia	1/66 (1.5%)	1	0/19 (0%)	0
End stage renal disease	1/66 (1.5%)	1	0/19 (0%)	0
Hydronephrosis	1/66 (1.5%)	1	0/19 (0%)	0
Respiratory, thoracic and mediastinal disorders
Lung disorder	1/66 (1.5%)	1	0/19 (0%)	0
Vascular disorders
Hypertension	5/66 (7.6%)	6	0/19 (0%)	0
Hypotension	1/66 (1.5%)	1	0/19 (0%)	0
Vena cava thrombosis	1/66 (1.5%)	1	0/19 (0%)	0
Venous thrombosis	1/66 (1.5%)	1	0/19 (0%)	0
Malignant hypertension	0/66 (0%)	0	1/19 (5.3%)	1
Other (Not Including Serious) Adverse Events
	PA21 (Velphoro®)		Calcium Acetate (Phoslyra®)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/66 (68.2%)		14/19 (73.7%)
Ear and labyrinth disorders
Otorrhoea	0/66 (0%)	0	1/19 (5.3%)	1
Endocrine disorders
Hyperparathyroidism	2/66 (3%)	3	1/19 (5.3%)	1
Hyperparathyroidism secondary	1/66 (1.5%)	2	1/19 (5.3%)	1
Gastrointestinal disorders
Diarrhoea	12/66 (18.2%)	14	0/19 (0%)	0
Nausea	8/66 (12.1%)	10	2/19 (10.5%)	2
Vomiting	6/66 (9.1%)	6	2/19 (10.5%)	3
Constipation	4/66 (6.1%)	4	1/19 (5.3%)	1
Abdominal pain	3/66 (4.5%)	3	1/19 (5.3%)	1
Abdominal pain upper	2/66 (3%)	2	1/19 (5.3%)	1
General disorders
Pyrexia	3/66 (4.5%)	3	1/19 (5.3%)	1
Catheter site haemorrhage	0/66 (0%)	0	1/19 (5.3%)	1
Infections and infestations
Urinary tract infection	3/66 (4.5%)	5	2/19 (10.5%)	3
Upper respiratory tract infection	2/66 (3%)	2	1/19 (5.3%)	2
Gastroenteritis	1/66 (1.5%)	1	1/19 (5.3%)	1
Pharyngitis	1/66 (1.5%)	1	1/19 (5.3%)	1
Clostridium difficile colitis	0/66 (0%)	0	1/19 (5.3%)	1
Clostridium difficile infection	0/66 (0%)	0	1/19 (5.3%)	1
Conjunctivitis	0/66 (0%)	0	1/19 (5.3%)	1
Cystitis	0/66 (0%)	0	1/19 (5.3%)	1
Hand-foot-and-mouth disease	0/66 (0%)	0	1/19 (5.3%)	1
Respiratory syncytial virus infection	0/66 (0%)	0	1/19 (5.3%)	1
Staphylococcal bacteraemia	0/66 (0%)	0	1/19 (5.3%)	1
Investigations
Blood lactate dehydrogenase increased	0/66 (0%)	0	1/19 (5.3%)	1
Blood phosphorus increased	0/66 (0%)	0	1/19 (5.3%)	1
Liver function test increased	0/66 (0%)	0	1/19 (5.3%)	1
Metabolism and nutrition disorders
Hypercalcaemia	4/66 (6.1%)	4	4/19 (21.1%)	4
Hyperphosphataemia	3/66 (4.5%)	3	3/19 (15.8%)	3
Hyperkalaemia	2/66 (3%)	3	1/19 (5.3%)	1
Hypophosphataemia	0/66 (0%)	0	1/19 (5.3%)	1
Iron deficiency	0/66 (0%)	0	1/19 (5.3%)	1
Metabolic acidosis	0/66 (0%)	0	1/19 (5.3%)	1
Nervous system disorders
Headache	2/66 (3%)	2	1/19 (5.3%)	1
Dizziness	0/66 (0%)	0	1/19 (5.3%)	1
Renal and urinary disorders
Dysuria	1/66 (1.5%)	1	1/19 (5.3%)	1
Haematuria	0/66 (0%)	0	1/19 (5.3%)	1
Reproductive system and breast disorders
Amenorrhoea	0/66 (0%)	0	1/19 (5.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	1/66 (1.5%)	1	2/19 (10.5%)	2
Sinus congestion	0/66 (0%)	0	1/19 (5.3%)	2
Skin and subcutaneous tissue disorders
Excessive granulation tissue	0/66 (0%)	0	1/19 (5.3%)	1
Pruritus	0/66 (0%)	0	1/19 (5.3%)	1
Rash	0/66 (0%)	0	1/19 (5.3%)	2

Limitations/Caveats

The study was prematurely ended as a result of the modification of study requirements, as agreed with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

No results of the Services or other information on the Clinical Study may be disclosed or submitted for publication or presentation without the Sponsor's prior written agreement.