A Randomized, Parallel, Open-Label Study to Compare Once-Daily Sevelamer Carbonate Powder Dosing With Thrice-Daily Sevelamer Hydrochloride Tablet Dosing in CKD Patients on Hemodialysis

Steven Fishbane, James Delmez, Wadi N. Suki, Srinivas K. Hariachar, Jeremy Heaton, Scott Chasan-Taber, Melissa A. Plone, Sharon Moe

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer, which may be suited to once-daily dosing. Study Design: Randomized parallel open-label study. Setting & Participants: Hemodialysis patients. Intervention: After a 2-week phosphate-binder washout, patients were randomly assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer hydrochloride tablets. Outcomes: Assessment of noninferiority with respect to change from baseline in serum phosphorus levels. Measurements: Serum phosphorus to 24 weeks. Results: After washout, mean serum phosphorus level decreased 2.0 ± 1.8 mg/dL (from 7.3 ± 1.3 mg/dL) for sevelamer carbonate and 2.9 ± 1.3 mg/dL (from 7.6 ± 1.3 mg/dL) for sevelamer hydrochloride (both P < 0.001). The upper CI bound was 1.50 mg/dL; therefore, noninferiority was not shown. 54% of sevelamer carbonate powder-treated patients and 64% of sevelamer hydrochloride tablet-treated patients had serum phosphorus levels within the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) target (≥3.5 and ≤5.5 mg/dL). Overall, the percentage of patients with treatment-emergent adverse events was similar between groups. However, a greater percentage of treatment-related upper gastrointestinal events, including nausea (10% vs 3%) and vomiting (6% vs 1%), were noted with sevelamer carbonate powder once daily. In addition, 4 (3%) sevelamer carbonate-treated patients experienced stimulation of the gag reflex and 2 (1%) experienced dislike of the taste with sevelamer carbonate powder. A greater percentage of sevelamer carbonate powder-treated patients discontinued treatment because of these treatment-related events or consent withdrawal. Limitations: Study was not blinded. Once-daily dose may not have been with the highest phosphate content meal; further exploration of alternative dosing schemes is warranted. Conclusions: Once-daily administration of sevelamer carbonate powder was not as effective in decreasing serum phosphorus levels as thrice-daily administration of sevelamer hydrochloride tablets. Nevertheless, once-daily sevelamer carbonate powder decreased serum phosphorus levels significantly, reaching the KDOQI phosphorus target in most patients. Therefore, once-daily dosing of sevelamer carbonate may be a reasonable alternative.

Original languageEnglish
Pages (from-to)307-315
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume55
Issue number2
DOIs
StatePublished - Feb 2010

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Powders
Tablets
Renal Dialysis
Phosphorus
Serum
Sevelamer
Kidney Diseases
Phosphates
Dosage Forms
Therapeutics
Nausea
Vomiting
Reflex
Meals
Suspensions

Keywords

  • once-daily dosing
  • Sevelamer carbonate
  • sevelamer hydrochloride

ASJC Scopus subject areas

  • Nephrology

Cite this

A Randomized, Parallel, Open-Label Study to Compare Once-Daily Sevelamer Carbonate Powder Dosing With Thrice-Daily Sevelamer Hydrochloride Tablet Dosing in CKD Patients on Hemodialysis. / Fishbane, Steven; Delmez, James; Suki, Wadi N.; Hariachar, Srinivas K.; Heaton, Jeremy; Chasan-Taber, Scott; Plone, Melissa A.; Moe, Sharon.

In: American Journal of Kidney Diseases, Vol. 55, No. 2, 02.2010, p. 307-315.

Research output: Contribution to journalArticle

Fishbane, Steven ; Delmez, James ; Suki, Wadi N. ; Hariachar, Srinivas K. ; Heaton, Jeremy ; Chasan-Taber, Scott ; Plone, Melissa A. ; Moe, Sharon. / A Randomized, Parallel, Open-Label Study to Compare Once-Daily Sevelamer Carbonate Powder Dosing With Thrice-Daily Sevelamer Hydrochloride Tablet Dosing in CKD Patients on Hemodialysis. In: American Journal of Kidney Diseases. 2010 ; Vol. 55, No. 2. pp. 307-315.
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abstract = "Background: Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer, which may be suited to once-daily dosing. Study Design: Randomized parallel open-label study. Setting & Participants: Hemodialysis patients. Intervention: After a 2-week phosphate-binder washout, patients were randomly assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer hydrochloride tablets. Outcomes: Assessment of noninferiority with respect to change from baseline in serum phosphorus levels. Measurements: Serum phosphorus to 24 weeks. Results: After washout, mean serum phosphorus level decreased 2.0 ± 1.8 mg/dL (from 7.3 ± 1.3 mg/dL) for sevelamer carbonate and 2.9 ± 1.3 mg/dL (from 7.6 ± 1.3 mg/dL) for sevelamer hydrochloride (both P < 0.001). The upper CI bound was 1.50 mg/dL; therefore, noninferiority was not shown. 54{\%} of sevelamer carbonate powder-treated patients and 64{\%} of sevelamer hydrochloride tablet-treated patients had serum phosphorus levels within the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) target (≥3.5 and ≤5.5 mg/dL). Overall, the percentage of patients with treatment-emergent adverse events was similar between groups. However, a greater percentage of treatment-related upper gastrointestinal events, including nausea (10{\%} vs 3{\%}) and vomiting (6{\%} vs 1{\%}), were noted with sevelamer carbonate powder once daily. In addition, 4 (3{\%}) sevelamer carbonate-treated patients experienced stimulation of the gag reflex and 2 (1{\%}) experienced dislike of the taste with sevelamer carbonate powder. A greater percentage of sevelamer carbonate powder-treated patients discontinued treatment because of these treatment-related events or consent withdrawal. Limitations: Study was not blinded. Once-daily dose may not have been with the highest phosphate content meal; further exploration of alternative dosing schemes is warranted. Conclusions: Once-daily administration of sevelamer carbonate powder was not as effective in decreasing serum phosphorus levels as thrice-daily administration of sevelamer hydrochloride tablets. Nevertheless, once-daily sevelamer carbonate powder decreased serum phosphorus levels significantly, reaching the KDOQI phosphorus target in most patients. Therefore, once-daily dosing of sevelamer carbonate may be a reasonable alternative.",
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AU - Fishbane, Steven

AU - Delmez, James

AU - Suki, Wadi N.

AU - Hariachar, Srinivas K.

AU - Heaton, Jeremy

AU - Chasan-Taber, Scott

AU - Plone, Melissa A.

AU - Moe, Sharon

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N2 - Background: Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer, which may be suited to once-daily dosing. Study Design: Randomized parallel open-label study. Setting & Participants: Hemodialysis patients. Intervention: After a 2-week phosphate-binder washout, patients were randomly assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer hydrochloride tablets. Outcomes: Assessment of noninferiority with respect to change from baseline in serum phosphorus levels. Measurements: Serum phosphorus to 24 weeks. Results: After washout, mean serum phosphorus level decreased 2.0 ± 1.8 mg/dL (from 7.3 ± 1.3 mg/dL) for sevelamer carbonate and 2.9 ± 1.3 mg/dL (from 7.6 ± 1.3 mg/dL) for sevelamer hydrochloride (both P < 0.001). The upper CI bound was 1.50 mg/dL; therefore, noninferiority was not shown. 54% of sevelamer carbonate powder-treated patients and 64% of sevelamer hydrochloride tablet-treated patients had serum phosphorus levels within the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) target (≥3.5 and ≤5.5 mg/dL). Overall, the percentage of patients with treatment-emergent adverse events was similar between groups. However, a greater percentage of treatment-related upper gastrointestinal events, including nausea (10% vs 3%) and vomiting (6% vs 1%), were noted with sevelamer carbonate powder once daily. In addition, 4 (3%) sevelamer carbonate-treated patients experienced stimulation of the gag reflex and 2 (1%) experienced dislike of the taste with sevelamer carbonate powder. A greater percentage of sevelamer carbonate powder-treated patients discontinued treatment because of these treatment-related events or consent withdrawal. Limitations: Study was not blinded. Once-daily dose may not have been with the highest phosphate content meal; further exploration of alternative dosing schemes is warranted. Conclusions: Once-daily administration of sevelamer carbonate powder was not as effective in decreasing serum phosphorus levels as thrice-daily administration of sevelamer hydrochloride tablets. Nevertheless, once-daily sevelamer carbonate powder decreased serum phosphorus levels significantly, reaching the KDOQI phosphorus target in most patients. Therefore, once-daily dosing of sevelamer carbonate may be a reasonable alternative.

AB - Background: Sevelamer carbonate powder for oral suspension is a new dosage form of sevelamer, which may be suited to once-daily dosing. Study Design: Randomized parallel open-label study. Setting & Participants: Hemodialysis patients. Intervention: After a 2-week phosphate-binder washout, patients were randomly assigned to once-daily sevelamer carbonate powder or thrice-daily sevelamer hydrochloride tablets. Outcomes: Assessment of noninferiority with respect to change from baseline in serum phosphorus levels. Measurements: Serum phosphorus to 24 weeks. Results: After washout, mean serum phosphorus level decreased 2.0 ± 1.8 mg/dL (from 7.3 ± 1.3 mg/dL) for sevelamer carbonate and 2.9 ± 1.3 mg/dL (from 7.6 ± 1.3 mg/dL) for sevelamer hydrochloride (both P < 0.001). The upper CI bound was 1.50 mg/dL; therefore, noninferiority was not shown. 54% of sevelamer carbonate powder-treated patients and 64% of sevelamer hydrochloride tablet-treated patients had serum phosphorus levels within the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) target (≥3.5 and ≤5.5 mg/dL). Overall, the percentage of patients with treatment-emergent adverse events was similar between groups. However, a greater percentage of treatment-related upper gastrointestinal events, including nausea (10% vs 3%) and vomiting (6% vs 1%), were noted with sevelamer carbonate powder once daily. In addition, 4 (3%) sevelamer carbonate-treated patients experienced stimulation of the gag reflex and 2 (1%) experienced dislike of the taste with sevelamer carbonate powder. A greater percentage of sevelamer carbonate powder-treated patients discontinued treatment because of these treatment-related events or consent withdrawal. Limitations: Study was not blinded. Once-daily dose may not have been with the highest phosphate content meal; further exploration of alternative dosing schemes is warranted. Conclusions: Once-daily administration of sevelamer carbonate powder was not as effective in decreasing serum phosphorus levels as thrice-daily administration of sevelamer hydrochloride tablets. Nevertheless, once-daily sevelamer carbonate powder decreased serum phosphorus levels significantly, reaching the KDOQI phosphorus target in most patients. Therefore, once-daily dosing of sevelamer carbonate may be a reasonable alternative.

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KW - Sevelamer carbonate

KW - sevelamer hydrochloride

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