Trial Outcomes & Findings for An Efficacy and Safety Study of Sevelamer Carbonate in Hyperphosphatemic Pediatric Participants With Chronic Kidney Disease (NCT NCT01574326)

Last Updated: 2016-07-25

Results Overview

Full analysis set for fixed dose period (FAS-FDP) participants were analyzed according to their randomized treatment. The change in serum phosphorus (mg/dL) from baseline to week 2 was calculated.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

101 participants

Primary outcome timeframe

Baseline, Week 2

Results posted on

2016-07-25

Participant Flow

The study was conducted at 29 centers in 4 countries. A total of 128 participants were screened between 11 May 2012 and 14 November 2014. Of whom, 101 participants were randomized and 27 were screen failures.

Participants were stratified in (1:1) by screening body surface area (BSA) (≥1.2 vs \<1.2 m\^2) \& qualifying serum phosphorus (≥7.0 vs \<7.0 mg/dL) to get sevelamer carbonate or placebo in 2 week fixed dose period (FDP). Following FDP, participants entered 26-week dose titration period (DTP) during which all participants received sevelamer carbonate.

Participant milestones

Participant milestones
Measure	FDP-Placebo for Sevelamer Carbonate, DTP-Sevelamer Carbonate Participants received placebo for sevelamer carbonate for 2 weeks in FDP and sevelamer carbonate for 26 weeks in DTP. Placebo matched to sevelamer carbonate 3 times a day (TID) for 2 weeks in FDP: 0.4 g TID for BSA \<0.75 m\^2 or 0.8 g TID for BSA ≥0.75 to \< 1.2 m\^2 as powder for oral suspension (POS) \& 1.6 g TID for BSA ≥1.2 m\^2 as POS/tablets as per participant's preference. If a child ate \<3 meals/snacks per day, dose was given with meals/snacks. In DTP, starting dose of sevelamer carbonate was based on screening BSA \& same as prescribed during FDP. Dose was titrated up/down every 2 weeks for 6 weeks \& then every 4 weeks to achieve a serum phosphorus level within age appropriate normal values or up to maximum dose as per Investigator's opinion. Dose titrations were based on BSA category: 0.2 g TID for BSA \<0.75 m\^2, 0.4 g TID for BSA ≥0.75 to \< 1.2 m\^2 \& 0.8 g TID for BSA ≥1.2 m\^2 (smaller titrations were permitted but could not be \<0.2 g TID with meals/snacks).	FDP-Sevelamer Carbonate, DTP-Sevelamer Carbonate Participants received sevelamer carbonate 0.4 g TID or 0.8 g TID or 1.6 g TID (based on screening BSA category) for 2 weeks in FDP and then continued to receive sevelamer carbonate in DTP. Sevelamer carbonate for 2 weeks in FDP: 0.4 g TID for BSA \<0.75 m\^2 or 0.8 g TID for BSA ≥0.75 to \< 1.2 m\^2 as POS or 1.6 g TID for BSA ≥1.2 m\^2 either as POS or tablets as per participant's preference. If a child ate \<3 meals/snacks per day, dose was given with meals/snacks. In DTP, starting dose of sevelamer carbonate was based on screening BSA \& same as dose prescribed during FDP. Dose was titrated up/down every 2 weeks for 6 weeks \& then every 4 weeks to achieve a serum phosphorus level within age appropriate normal values or up to maximum dose as per Investigator's opinion. Dose titrations were based on BSA category: by 0.2 g TID for BSA \<0.75 m\^2, 0.4 g TID for BSA ≥0.75 to \<1.2 m\^2 \& 0.8 g TID for BSA ≥1.2 m\^2 (smaller titrations were permitted but could not be \<0.2 g TID with meal/snacks).
Overall Study STARTED	51	50
Overall Study Treated	51	49
Overall Study COMPLETED	35	31
Overall Study NOT COMPLETED	16	19

Reasons for withdrawal

Reasons for withdrawal
Measure	FDP-Placebo for Sevelamer Carbonate, DTP-Sevelamer Carbonate Participants received placebo for sevelamer carbonate for 2 weeks in FDP and sevelamer carbonate for 26 weeks in DTP. Placebo matched to sevelamer carbonate 3 times a day (TID) for 2 weeks in FDP: 0.4 g TID for BSA \<0.75 m\^2 or 0.8 g TID for BSA ≥0.75 to \< 1.2 m\^2 as powder for oral suspension (POS) \& 1.6 g TID for BSA ≥1.2 m\^2 as POS/tablets as per participant's preference. If a child ate \<3 meals/snacks per day, dose was given with meals/snacks. In DTP, starting dose of sevelamer carbonate was based on screening BSA \& same as prescribed during FDP. Dose was titrated up/down every 2 weeks for 6 weeks \& then every 4 weeks to achieve a serum phosphorus level within age appropriate normal values or up to maximum dose as per Investigator's opinion. Dose titrations were based on BSA category: 0.2 g TID for BSA \<0.75 m\^2, 0.4 g TID for BSA ≥0.75 to \< 1.2 m\^2 \& 0.8 g TID for BSA ≥1.2 m\^2 (smaller titrations were permitted but could not be \<0.2 g TID with meals/snacks).	FDP-Sevelamer Carbonate, DTP-Sevelamer Carbonate Participants received sevelamer carbonate 0.4 g TID or 0.8 g TID or 1.6 g TID (based on screening BSA category) for 2 weeks in FDP and then continued to receive sevelamer carbonate in DTP. Sevelamer carbonate for 2 weeks in FDP: 0.4 g TID for BSA \<0.75 m\^2 or 0.8 g TID for BSA ≥0.75 to \< 1.2 m\^2 as POS or 1.6 g TID for BSA ≥1.2 m\^2 either as POS or tablets as per participant's preference. If a child ate \<3 meals/snacks per day, dose was given with meals/snacks. In DTP, starting dose of sevelamer carbonate was based on screening BSA \& same as dose prescribed during FDP. Dose was titrated up/down every 2 weeks for 6 weeks \& then every 4 weeks to achieve a serum phosphorus level within age appropriate normal values or up to maximum dose as per Investigator's opinion. Dose titrations were based on BSA category: by 0.2 g TID for BSA \<0.75 m\^2, 0.4 g TID for BSA ≥0.75 to \<1.2 m\^2 \& 0.8 g TID for BSA ≥1.2 m\^2 (smaller titrations were permitted but could not be \<0.2 g TID with meal/snacks).
Overall Study Randomized but not treated	0	1
Overall Study Withdrawal by Participant	2	4
Overall Study Physician Decision	5	3
Overall Study Adverse Event	1	3
Overall Study Other: Mainly kidney transplant	8	8

Baseline Characteristics

An Efficacy and Safety Study of Sevelamer Carbonate in Hyperphosphatemic Pediatric Participants With Chronic Kidney Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FDP-Placebo for Sevelamer Carbonate, DTP-Sevelamer Carbonate n=51 Participants Participants received placebo for sevelamer carbonate for 2 weeks in FDP and sevelamer carbonate for 26 weeks in DTP. Placebo matched to sevelamer carbonate TID for 2 weeks in FDP: 0.4 g TID for BSA \<0.75 m\^2 or 0.8 g TID for BSA ≥0.75 to \< 1.2 m\^2 POS and 1.6 g TID for BSA ≥1.2 m\^2 as POS/tablets as per participant's preference. If a child ate \<3 meals/snacks per day, dose was given with meals/snacks. In DTP, starting dose of sevelamer carbonate was based on screening BSA \& same as prescribed during FDP. Dose was titrated up/down every 2 weeks for 6 weeks \& then every 4 weeks to achieve a serum phosphorus level within age appropriate normal values or up to maximum dose as per Investigator's opinion. Dose titrations were based on BSA category: 0.2 g TID for BSA \<0.75 m\^2, 0.4 g TID for BSA ≥0.75 to \< 1.2 m\^2 \& 0.8 g TID for BSA ≥1.2 m\^2 (smaller titrations were permitted but could not be \<0.2 g TID with meals/snacks).	FDP-Sevelamer Carbonate, DTP-Sevelamer Carbonate n=50 Participants Participants received sevelamer carbonate 0.4 g TID or 0.8 g TID or 1.6 g TID (based on screening BSA category) for 2 weeks in FDP and then continued to receive sevelamer carbonate in DTP. Sevelamer carbonate for 2 weeks in FDP: 0.4 g TID for BSA \<0.75 m\^2 or 0.8 g TID for BSA ≥0.75 to \< 1.2 m\^2 as POS or 1.6 g TID for BSA ≥1.2 m\^2 either as POS or tablets as per participant's preference. If a child ate \<3 meals/snacks per day, dose was given with meals/snacks. In DTP, starting dose of sevelamer carbonate was based on screening BSA \& same as dose prescribed during FDP. Dose was titrated up/down every 2 weeks for 6 weeks \& then every 4 weeks to achieve a serum phosphorus level within age appropriate normal values or up to maximum dose as per Investigator's opinion. Dose titrations were based on BSA category: by 0.2 g TID for BSA \<0.75 m\^2, 0.4 g TID for BSA ≥0.75 to \<1.2 m\^2 \& 0.8 g TID for BSA ≥1.2 m\^2 (smaller titrations were permitted but could not be \<0.2 g TID with meal/snacks).	Total n=101 Participants Total of all reporting groups
Age, Continuous	14.3 years STANDARD_DEVIATION 3.11 • n=5 Participants	13.9 years STANDARD_DEVIATION 2.75 • n=7 Participants	14.1 years STANDARD_DEVIATION 2.93 • n=5 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	19 Participants n=7 Participants	37 Participants n=5 Participants
Sex: Female, Male Male	33 Participants n=5 Participants	31 Participants n=7 Participants	64 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 2

Population: FAS-FDP population included all treated participants with a baseline phosphorus value and at least 1 post-baseline assessment after the first dose of study drug and on or before Week 2. Three participants (1 in sevelamer carbonate group and 2 in placebo group) were excluded from FAS-FDP due to no baseline phosphorus value at week 2.

Full analysis set for fixed dose period (FAS-FDP) participants were analyzed according to their randomized treatment. The change in serum phosphorus (mg/dL) from baseline to week 2 was calculated.

Outcome measures

Outcome measures
Measure	FDP-Placebo for Sevelamer Carbonate n=49 Participants Participants received placebo for sevelamer carbonate for first 2 weeks in FDP.	FDP-Sevelamer Carbonate n=48 Participants Participants received sevelamer carbonate 0.4 g TID or 0.8 g TID or 1.6 g TID (based on the screening BSA category) for 2 weeks in FDP.
Change From Baseline (Week 0) to Week 2 in Serum Phosphorus At Baseline	7.2 mg/dL Standard Deviation 1.841	7.2 mg/dL Standard Deviation 2.09
Change From Baseline (Week 0) to Week 2 in Serum Phosphorus At Week 2	7.24 mg/dL Standard Deviation 2.029	6.34 mg/dL Standard Deviation 1.306
Change From Baseline (Week 0) to Week 2 in Serum Phosphorus Change from baseline to Week 2	0.04 mg/dL Standard Deviation 1.478	-0.87 mg/dL Standard Deviation 1.649

PRIMARY outcome

Timeframe: Up to 32 weeks (up to 4 weeks washout period, 2 weeks FDP and 26 weeks DTP)

Population: Analysis was performed on safety set, which included all enrolled participants who received at least 1 dose of study drug. Participants were analyzed according to actual received treatment.

A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. AEs from the time of signing the informed consent through the end of the study for all participants. SAEs occurring during the 15 days following study completion or early termination were also to be collected.

Outcome measures

Outcome measures
Measure	FDP-Placebo for Sevelamer Carbonate n=51 Participants Participants received placebo for sevelamer carbonate for first 2 weeks in FDP.	FDP-Sevelamer Carbonate n=49 Participants Participants received sevelamer carbonate 0.4 g TID or 0.8 g TID or 1.6 g TID (based on the screening BSA category) for 2 weeks in FDP.
Treatment - Emergent Adverse Events (AEs) Any AE: FDP	20 participants	19 participants
Treatment - Emergent Adverse Events (AEs) AE related: FDP	3 participants	2 participants
Treatment - Emergent Adverse Events (AEs) Any SAE: FDP	1 participants	4 participants
Treatment - Emergent Adverse Events (AEs) SAE related: FDP	0 participants	0 participants
Treatment - Emergent Adverse Events (AEs) Any AE Leading to Study Drug Discontinuation: FDP	1 participants	1 participants
Treatment - Emergent Adverse Events (AEs) Any AE: DTP	42 participants	35 participants
Treatment - Emergent Adverse Events (AEs) AE related: DTP	9 participants	4 participants
Treatment - Emergent Adverse Events (AEs) Any SAE: DTP	14 participants	17 participants
Treatment - Emergent Adverse Events (AEs) SAE related: DTP	2 participants	2 participants
Treatment - Emergent Adverse Events (AEs) Any AE Leading to Study Drug Discontinuation: DTP	0 participants	3 participants
Treatment - Emergent Adverse Events (AEs) Deaths	0 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, Week 28/Early Termination

Population: FAS-DTP population included all treated participants with a baseline phosphorus value and at least 1 post-baseline phosphorus assessment after Week 2. Five participants (3 in sevelamer carbonate group and 2 in the placebo group) were excluded from the FAS-DTP due to no baseline phosphorus value or no phosphorus assessment after Week 2.

Full analysis set for dose titration period (FAS-DTP) participants were analyzed according to their randomized treatment. The change in serum phosphorus (mg/dL) from baseline to Week 28/Early Termination was calculated.

Outcome measures

Outcome measures
Measure	FDP-Placebo for Sevelamer Carbonate n=49 Participants Participants received placebo for sevelamer carbonate for first 2 weeks in FDP.	FDP-Sevelamer Carbonate n=46 Participants Participants received sevelamer carbonate 0.4 g TID or 0.8 g TID or 1.6 g TID (based on the screening BSA category) for 2 weeks in FDP.
Change From Baseline (Week 0) to Week 28/Early Termination in Serum Phosphorus At Baseline (Week 0)	7.05 mg/dL Standard Deviation 1.797	7.28 mg/dL Standard Deviation 2.103
Change From Baseline (Week 0) to Week 28/Early Termination in Serum Phosphorus At Week 28 / Early Termination	5.92 mg/dL Standard Deviation 1.612	6.04 mg/dL Standard Deviation 1.878
Change From Baseline (Week 0) to Week 28/Early Termination in Serum Phosphorus Change from Baseline to Week 28/Early Termination	-1.13 mg/dL Standard Deviation 2.061	-1.23 mg/dL Standard Deviation 2.206

Adverse Events

FDP - Placebo

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

FDP - Sevelamer Carbonate

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

DTP - Sevelamer Carbonate

Serious events: 31 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Genzyme Corporation

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Publication restrictions are in place

Restriction type: OTHER