EFFICACY

EFFICACY

XPHOZAH CLINICAL TRIALS

XPHOZAH: Proven phosphate reduction in three phase 3 trials1

03
Phase 3
trials1
1k+
Patients with CKD
on dialysis1

PHREEDOM

Long-term trial (52-week) evaluating XPHOZAH monotherapy (n=564)1,2

Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM)2

Geoffrey A. Block, Anthony J. Bleyer, Arnold L. Silva, Daniel E. Weiner, Robert I. Lynn, Yang Yang, David P. Rosenbaum, and Glenn M. Chertow; on behalf of the PHREEDOM Trial Investigators

As published in Kidney 360.

PHREEDOM Trial Design

PHREEDOM included a 26-week, active-controlled, open-label, randomized treatment period, followed by a 12-week, double-blind, placebo-controlled, randomized withdrawal period.

A total of 564 patients were randomized into the 26-week treatment period (423 to XPHOZAH and 141 to the safety control arm). Among the 423 patients randomized to XPHOZAH 30 mg BID, 255 patients (60%) completed the 26-week treatment period and were re-randomized 1:1 to remain on XPHOZAH (n=128) or receive placebo (n=127).2

PHREEDOM Trial Design2,3

Chart of PHREEDOM study design

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Select Inclusion Criteria2
  • ≥18 years of age
  • On maintenance HD or PD
  • On phosphate binder with serum phosphorus levels ≥4 mg/dL and ≤8 mg/dL prior to phosphate-binder washout
  • Following phosphate-binder washout, serum phosphorus levels ≥6 mg/dL and ≤10 mg/dL and must have had an increase of ≥1.5 mg/dL vs pre-washout value
Select Exclusion Criteria2
  • Intact PTH >1200 pg/mL

*167 patients discontinued from the study, and 1 patient was excluded from re-randomization due to physician decision.
*Includes all eligible patients who completed the randomized withdrawal period from either the XPHOZAH or placebo arm.

Key Efficacy Endpoint Result—Full Analysis Set

During the randomized withdrawal period, the serum phosphorus concentration rose in the placebo group by 0.7 mg/dL (P=0.002) relative to patients who remained on XPHOZAH.1

Primary Endpoint Result—Prespecified Responder Population

56% of patients from the full analysis set who were part of the randomized withdrawal period met the prespecified responder definition of a serum phosphorus reduction ≥1.2 mg/dL at the end of the randomized treatment period on XPHOZAH.4

During the randomized withdrawal period, the serum phosphorus concentration rose in the placebo group by 1.4 mg/dL (P<0.001) relative to patients who remained on XPHOZAH.2

Limitation
Safety

HD = hemodialysis; PD = peritoneal dialysis; PTH = parathyroid hormone; R = randomized; BID = twice daily.

BLOCK

Short-term trial (12-week) evaluating XPHOZAH monotherapy (n=219)1,5

Efficacy and Safety of Tenapanor in Patients With Hyperphosphatemia Receiving Maintenance Hemodialysis: A Randomized Phase 3 Trial

Geoffrey A. Block, David P. Rosenbaum, Andrew Yan, and Glenn M. Chertow

As published in the Journal of the American Society of Nephrology.

BLOCK Trial Design5

BLOCK included an 8-week, randomized, double-blind treatment period that evaluated three dosing regimens of XPHOZAH (3 mg twice daily, 10 mg twice daily, or a 30 mg twice daily titration regimen).

This was followed by a 4-week, double-blind, placebo-controlled, randomized withdrawal period during which patients were re-randomized 1:1 to their current XPHOZAH treatment or to placebo. Of the 219 patients included in the trial, 164 patients (75%) completed the 8-week randomized treatment period on XPHOZAH and were re-randomized 1:1 to remain on XPHOZAH (n=82) or receive placebo (n=82).

BLOCK Trial Design5

Chart of BLOCK study design

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Select Inclusion Criteria5
  • ≥18 years of age
  • On maintenance HD
  • On phosphate binders and serum phosphorus levels ≥4.0 mg/dL and ≤7.0 mg/dL prior to phosphate-binder washout
  • Following phosphate-binder washout, serum phosphorus levels ≥6.0 mg/dL and <10.0 mg/dL and must have had an increase of ≥1.5 mg/dL vs pre-washout value
Select Exclusion Criteria5
  • Intact PTH >1200 pg/mL
  • Serum phosphorus levels >10.0 mg/dL at any point in prior 3 months, serum bicarbonate <18 mmol/L on 2 consecutive measurements
  • Diarrhea/loose stool during the week prior to randomization
  • Life expectancy <6 months

Key Efficacy Endpoint Result—Full Analysis Set

During the randomized withdrawal period, the serum phosphorus concentration rose in the placebo group by 0.7 mg/dL (P=0.003) relative to patients who remained on XPHOZAH.1

Primary Endpoint Result—Prespecified Responder Population

49% of patients from the full analysis set who were part of the randomized withdrawal period met the prespecified responder definition of a serum phosphorus reduction ≥1.2 mg/dL at the end of the randomized treatment period on XPHOZAH.6

During the randomized withdrawal period, the serum phosphorus concentration rose in the placebo group by 0.8 mg/dL (P=0.01) relative to patients who remained on XPHOZAH.5

Limitation
Safety

Incidence of diarrhea and discontinuation due to diarrhea are shown for patients started on the 30 mg BID dose.5

BID = twice daily; HD = hemodialysis; PTH = parathyroid hormone; R = randomized.

AMPLIFY

A short-term trial (4-week) evaluating XPHOZAH as add-on therapy to phosphate binders (n=236)1,7

A Randomized Trial of Tenapanor and Phosphate Binders as a Dual-Mechanism Treatment for Hyperphosphatemia in Patients on Maintenance Dialysis (AMPLIFY)

Pablo E. Pergola, David P. Rosenbaum, Yang Yang, and Glenn M. Chertow

As published in Journal of the American Society of Nephrology.

AMPLIFY Trial Design7

AMPLIFY was a randomized, parallel-group, double-blind, placebo-controlled study that evaluated the effect of XPHOZAH on the change in serum phosphorus when used as add-on therapy in patients on stable phosphate-binder therapy with serum phosphorus ≥5.5 mg/dL.

A total of 236 patients were randomized to receive XPHOZAH (n=117) or placebo (n=119) BID for 4 weeks.

AMPLIFY Trial Design7

Image: Chart of AMPLIFY study design

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Select Inclusion Criteria7
  • ≥18 years of age
  • On maintenance HD or PD
  • On phosphate binder with serum phosphorus levels ≥5.5 mg/dL and ≤10.0 mg/dL at time of screening and at the end of the run-in period
Select Exclusion Criteria7
  • Intact PTH >1200 pg/mL
  • Clinical signs of hypovolemia at screening
  • History of inflammatory bowel disease/irritable bowel syndrome with diarrhea

Primary Endpoint Result

At week 4, the serum phosphorus decreased by 0.7 mg/dL (P=0.0004) in the add-on XPHOZAH group as compared with the add-on placebo group.1

Additional Efficacy Endpoint Result

Approximately 2x more patients achieved the serum phosphorus treatment goal of <5.5 mg/dL with XPHOZAH and a phosphate binder compared with phosphate binders alone (P<0.01).7
Limitation
Safety

BID = twice daily; CI = confidence interval; HD = hemodialysis; PD = peritoneal dialysis; PTH = parathyroid hormone.

RELATED LINKS

Safety

Dosing

REFERENCES

1.

XPHOZAH [prescribing information]. Waltham, MA: Ardelyx, Inc.; 2023.

2.

Block GA, Bleyer AJ, Silva AL, et al. Safety and efficacy of tenapanor for long-term serum phosphate control in maintenance dialysis: a 52-week randomized phase 3 trial (PHREEDOM). Kidney360. 2021;2(10):1600-1610.

3.

Data on file. Ardelyx, Inc. 2020.

4.

Data on file. Ardelyx, Inc. 2020.

5.

Block GA, Rosenbaum DP, Yan A, Chertow GM. Efficacy and safety of tenapanor in patients with hyperphosphatemia receiving maintenance hemodialysis: a randomized phase 3 trial. J Am Soc Nephrol. 2019;30(4):641-652.

6.

Data on file. Ardelyx, Inc. 2023.

7.

Pergola PE, Rosenbaum DP, Yang Y, Chertow GM. A randomized trial of tenapanor and phosphate binders as a dual-mechanism treatment for hyperphosphatemia in patients on maintenance dialysis (AMPLIFY). J Am Soc Nephrol. 2021;32(6):1465-1473.

Indication

XPHOZAH (tenapanor) 30 mg BID is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.

Important Safety Information

Contraindications

XPHOZAH is contraindicated in:

  • Pediatric patients under 6 years of age
  • Patients with known or suspected mechanical gastrointestinal obstruction

Warnings and precautions

Diarrhea

Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea.

Most Common Adverse Reactions

Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials.

For additional safety information, please see full Prescribing Information.

Indication

XPHOZAH (tenapanor) 30 mg BID is indicated to reduce serum phosphorus in adults with chronic kidney disease (CKD) on dialysis as add-on therapy in patients who have an inadequate response to phosphate binders or who are intolerant of any dose of phosphate binder therapy.

Important Safety Information

Contraindications

XPHOZAH is contraindicated in:

  • Pediatric patients under 6 years of age
  • Patients with known or suspected mechanical gastrointestinal obstruction

Warnings and precautions

Diarrhea

Patients may experience severe diarrhea. Treatment with XPHOZAH should be discontinued in patients who develop severe diarrhea.

Most Common Adverse Reactions

Diarrhea, which occurred in 43-53% of patients, was the only adverse reaction reported in at least 5% of XPHOZAH-treated patients with CKD on dialysis across trials. The majority of diarrhea events in XPHOZAH-treated patients were reported to be mild-to-moderate in severity and resolved over time, or with dose reduction. Diarrhea was typically reported soon after initiation but could occur at any time during treatment with XPHOZAH. Severe diarrhea was reported in 5% of XPHOZAH-treated patients in these trials.

For additional safety information, please see full Prescribing Information.

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