Trial Outcomes & Findings for A Phase 3 Study to Investigate the Safety and Efficacy of PA21, a Phosphate Binder, in Dialysis Patients (NCT NCT01324128)

Last Updated: 2014-04-24

Results Overview

Change in serum phosphorus levels compared between PA21 Maintenance Dose (MD) and PA21-1 Low Dose (LD) in Stage 2 from Week 24 to Week 27

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1059 participants

Primary outcome timeframe

Week 24, Week 27

Results posted on

2014-04-24

Participant Flow

The first 100HD subjects that completed Stage 1 in the PA21 treatment group entered Stage 2 and were randomised to PA21 Maintenance Dose (MD) or PA21-1 Low Dose (LD). Due to a randomisation error only 99 subjects were randomised into Stage 2.

Participant milestones

Participant milestones
Measure	PA21 Stage 1 PA21 (2.5 g tablet). Dose range of 5.0 g/day (2 tablets/day) to 15.0 g/day (6 tablets/day).	Sevelamer Carbonate Stage 1 Sevelamer carbonate. Dose range of 2.4 g/day (3 tablets/day) to 14.4 g/day (18 tablets/day).	PA21 (MD) Stage 2 PA21 Maintenance Dose (MD). Continuation of same dose that was being received at the end of Stage 1	PA21-1 (LD) Stage 2 PA21-1 (1.25 g/day) Low Dose (LD) comparator for Stage 2.
Stage 1 STARTED	710	349	0	0
Stage 1 COMPLETED	515	293	0	0
Stage 1 NOT COMPLETED	195	56	0	0
Stage 2 STARTED	0	0	50	49
Stage 2 COMPLETED	0	0	42	46
Stage 2 NOT COMPLETED	0	0	8	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 3 Study to Investigate the Safety and Efficacy of PA21, a Phosphate Binder, in Dialysis Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PA21 Stage 1 n=710 Participants PA21 (2.5 g tablet). Dose range of 5.0 g/day (2 tablets/day) to 15.0 g/day (6 tablets/day).	Sevelamer Carbonate Stage 1 n=349 Participants Sevelamer carbonate. Dose range of 2.4 g/day (3 tablets/day) to 14.4 g/day (18 tablets/day).	Total n=1059 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	512 Participants n=5 Participants	242 Participants n=7 Participants	754 Participants n=5 Participants
Age, Categorical >=65 years	198 Participants n=5 Participants	107 Participants n=7 Participants	305 Participants n=5 Participants
Age, Continuous	56.3 years STANDARD_DEVIATION 13.35 • n=5 Participants	55.8 years STANDARD_DEVIATION 14.59 • n=7 Participants	56.2 years STANDARD_DEVIATION 13.77 • n=5 Participants
Sex: Female, Male Female	314 Participants n=5 Participants	129 Participants n=7 Participants	443 Participants n=5 Participants
Sex: Female, Male Male	396 Participants n=5 Participants	220 Participants n=7 Participants	616 Participants n=5 Participants
Region of Enrollment United States	345 participants n=5 Participants	171 participants n=7 Participants	516 participants n=5 Participants
Region of Enrollment Europe	159 participants n=5 Participants	77 participants n=7 Participants	236 participants n=5 Participants
Region of Enrollment Russian Federation	101 participants n=5 Participants	50 participants n=7 Participants	151 participants n=5 Participants
Region of Enrollment Ukraine	34 participants n=5 Participants	17 participants n=7 Participants	51 participants n=5 Participants
Region of Enrollment Serbia	47 participants n=5 Participants	24 participants n=7 Participants	71 participants n=5 Participants
Region of Enrollment Croatia	19 participants n=5 Participants	8 participants n=7 Participants	27 participants n=5 Participants
Region of Enrollment South Africa	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 24, Week 27

Population: For the Primary Outcome, data from the Primary Efficacy Set (PES) was used. The PES consists of subjects who were randomized to Stage 2 and received at least 1 dose of study medication during Stage 2 and had at least 1 post-baseline (Stage 2) efficacy assessment in Stage 2.

Change in serum phosphorus levels compared between PA21 Maintenance Dose (MD) and PA21-1 Low Dose (LD) in Stage 2 from Week 24 to Week 27

Outcome measures

Outcome measures
Measure	PA21 (MD) Stage 2 n=44 Participants PA21 Stage 2 Maintenance Dose (MD). Continuation of same dose that was being received at the end of Stage 1.	PA21-1 (LD) Stage 2 n=49 Participants PA21-1 Low Dose (LD) comparator (1.25 g/day) for Stage 2
Change in Serum Phosphorus Levels From Week 24 to Week 27	0.25 mg/dL Standard Deviation 0.23	1.92 mg/dL Standard Deviation 0.23

SECONDARY outcome

Timeframe: Week 12 post Baseline

Population: For the Secondary Outcome, data from the Per Protocol Set (PPS) was used. The PPS consists of all subjects who had completed the analysis dose titration period (baseline to Week 12), had at least 1 evaluable serum phosphorus result at or after Week 12, and had no major protocol deviations.

Change in serum phosphorus levels from baseline to Week 12 in the PA21 group versus the sevelamer group.

Outcome measures

Outcome measures
Measure	PA21 (MD) Stage 2 n=461 Participants PA21 Stage 2 Maintenance Dose (MD). Continuation of same dose that was being received at the end of Stage 1.	PA21-1 (LD) Stage 2 n=224 Participants PA21-1 Low Dose (LD) comparator (1.25 g/day) for Stage 2
Change in Serum Phosphorus Levels From Baseline to Week 12	-2.19 mg/dL Standard Error 0.09	-2.45 mg/dL Standard Error 0.11

Adverse Events

PA21 Stage 1

Serious events: 129 serious events

Other events: 426 other events

Deaths: 0 deaths

Sevelamer Carbonate Stage 1

Serious events: 69 serious events

Other events: 162 other events

Deaths: 0 deaths

PA21-1 (LD) Stage 2

Serious events: 6 serious events

Other events: 10 other events

Deaths: 0 deaths

PA21 (MD) Stage 2

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	PA21 Stage 1 n=707 participants at risk PA21 (2.5 g tablet). Dose range of 5.0 g/day (2 tablets/day) to 15.0 g/day (6 tablets/day).	Sevelamer Carbonate Stage 1 n=348 participants at risk Sevelamer carbonate. Dose range of 2.4 g/day (3 tablets/day) to 14.4 g/day (18 tablets/day).	PA21-1 (LD) Stage 2 n=49 participants at risk PA21-1 (1.25 g tablet). Low Dose (LD) comparator (1.25 g/day) for Stage 2.	PA21 (MD) Stage 2 n=45 participants at risk PA21 (2.5g tablet) Maintenance Dose (MD). Continuation of same dose that was being received at the end of Stage 1.
Gastrointestinal disorders Diarrhoea	20.1% 142/707 • Number of events 184 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	7.5% 26/348 • Number of events 31 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	2.0% 1/49 • Number of events 1 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	2.2% 1/45 • Number of events 1 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.
Gastrointestinal disorders Faeces discoloured	15.4% 109/707 • Number of events 110 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.29% 1/348 • Number of events 1 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/49 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/45 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Hyperphosphataemia	11.2% 79/707 • Number of events 114 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	7.8% 27/348 • Number of events 39 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	14.3% 7/49 • Number of events 7 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/45 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.
Gastrointestinal disorders Nausea	7.2% 51/707 • Number of events 60 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	11.2% 39/348 • Number of events 41 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/49 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	2.2% 1/45 • Number of events 1 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.
Vascular disorders Hypertension	6.4% 45/707 • Number of events 54 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	7.5% 26/348 • Number of events 39 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/49 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/45 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.
Gastrointestinal disorders Vomiting	4.4% 31/707 • Number of events 36 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	5.5% 19/348 • Number of events 22 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/49 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/45 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.
Skin and subcutaneous tissue disorders Pruritus	3.3% 23/707 • Number of events 25 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	2.0% 7/348 • Number of events 7 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	6.1% 3/49 • Number of events 3 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/45 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.
Gastrointestinal disorders Constipation	3.8% 27/707 • Number of events 33 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	7.2% 25/348 • Number of events 26 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/49 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.	0.00% 0/45 For the serious adverse event (SAE) and adverse event (AE) listings, data from the Safety Set (SS) was used. The SS consists of all randomised subjects who received at least 1 dose of study treatment.

Additional Information

Medical Information

Vifor Pharma

Phone: 41 58 851 8222

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Investigators may not present or publish partial or complete study results individually. Any manuscript or abstract proposed by the Investigators must be reviewed and approved in writing by Vifor Pharma before submission for publication. Names of all Investigators participating in the study will be included in the publication.
Publication restrictions are in place

Restriction type: OTHER