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A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis

Primary Purpose

Hyperphosphatemia

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Tenapanor

Placebo

Sevelamer Carbonate

About this trial

This is an interventional treatment trial for Hyperphosphatemia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Females must be non-pregnant, non-lactating, and either be post-menopausal for at least 12 months, have documentation of irreversible surgical sterilization, or confirm the use of one of the acceptable contraceptive methods
Males must agree to avoid fathering a child and agree to use an appropriate method of contraception
Chronic maintenance hemodialysis 3x a week for at least 3 months
Chronic maintenance peritoneal dialysis for a minimum of 6 months
Kt/V ≥ 1.2 at most recent measurement prior to screening
Prescribed and taking at least 3 doses of phosphate binder per day
Serum phosphorus levels should be between 4.0 and 8.0 mg/dL at screening
Unchanged dose of vitamin D or calcimimetics for the last 4 weeks prior to screening
For enrollment in the study after at least 2 weeks of wash-out, subjects must have serum phosphorus levels of at least 6.0 mg/dL but not more than 10.0 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value after 2 or 3 weeks wash-out of phosphate binders

Exclusion Criteria:

Severe hyperphosphatemia defined as serum phosphorus greater than 10.0 mg/dL on phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening visit
Serum/plasma parathyroid hormone >1200 pg/mL
Clinical signs of hypovolemia at enrollment
History of IBD or IBS-D
Scheduled for living donor kidney transplant, change to peritoneal dialysis, home HD or plans to relocate to another center during the study period
Positive serology with evidence of significant hepatic impairment or WBC elevation according to the Investigator
Life expectancy <6 months
Previous exposure to tenapanor

Sites / Locations

Site 529
Wake Forest School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Active Comparator

Arm Label

Tenapanor 10 mg, 20 mg, 30 mg BID

Placebo

Sevelamer Carbonate

Arm Description

During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID

Placebo

Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care)

Outcomes

Primary Outcome Measures

Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the Responder Population

Patients with at least a 1.2 mg/dL decrease in serum phosphorus during the first 26 weeks of the study were defined as the responder population.

Secondary Outcome Measures

Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the ITT Population

Placebo Adjusted Change in Serum Phosphorus from the beginning to the end of the Randomized Withdrawal Period in all patients

Serum Phosphorus From Baseline

Serum Phosphorus from baseline (post washout) to end of 26 week period

Full Information

NCT ID

NCT03427125

First Posted

January 19, 2018

Last Updated

June 8, 2023

Sponsor

Ardelyx

1. Study Identification

Unique Protocol Identification Number

NCT03427125

Brief Title

A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis

Official Title

A 26-Wk, Phase 3, Open Label (OL) Study With a 12-Wk, Placebo-Controlled, Randomized Withdrawal Period and an OL Safety Extension to Evaluate the Safety and Efficacy of Tenapanor to Treat Hyperphosphatemia in CKD Patients on Dialysis

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Completed

Study Start Date

January 8, 2018 (Actual)

Primary Completion Date

November 15, 2019 (Actual)

Study Completion Date

February 27, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ardelyx

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This Phase 3, 26-week, open label study with a 12-week, placebo-controlled, randomized withdrawal period followed by an open label long term safety extension will evaluate the safety and efficacy of tenapanor to treat hyperphosphatemia in end-stage renal disease (ESRD) on hemodialysis and peritoneal dialysis.

Detailed Description

The study consists of a screening visit, a phosphate binder-free washout period of up to 4 weeks, a 26-week treatment period, an up to 12-week placebo-controlled, randomized withdrawal period, during which patients are randomized 1:1 to either remain on their tenapanor treatment or placebo, followed by an open label safety extension period for a total treatment period of up to 52 weeks. An active control group, for safety analysis only, will receive sevelamer carbonate, open label, for the entire 52-week study period Depending on increase in serum phosphate (s-P) levels, subjects can be randomized 2 or 3 weeks after being taken off their phosphate lowering medication. Subjects who qualify to enroll in the study will be randomized 3:1 to either receive tenapanor at a dose of 30 mg bid or sevelamer carbonate.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hyperphosphatemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

1559 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tenapanor 10 mg, 20 mg, 30 mg BID

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo

Arm Title

Sevelamer Carbonate

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Tenapanor

Other Intervention Name(s)

RDX5791, AZD1722

Intervention Description

Active Drug

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Inactive Drug

Intervention Type

Drug

Intervention Name(s)

Sevelamer Carbonate

Other Intervention Name(s)

Renvela

Intervention Description

Active control

Primary Outcome Measure Information:

Title

Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the Responder Population

Description

Patients with at least a 1.2 mg/dL decrease in serum phosphorus during the first 26 weeks of the study were defined as the responder population.

Time Frame

12 weeks (randomized withdrawal period)

Secondary Outcome Measure Information:

Title

Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the ITT Population

Description

Placebo Adjusted Change in Serum Phosphorus from the beginning to the end of the Randomized Withdrawal Period in all patients

Time Frame

12 weeks (randomized withdrawal period)

Title

Serum Phosphorus From Baseline

Description

Serum Phosphorus from baseline (post washout) to end of 26 week period

Time Frame

26 weeks (open label treatment period)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Females must be non-pregnant, non-lactating, and either be post-menopausal for at least 12 months, have documentation of irreversible surgical sterilization, or confirm the use of one of the acceptable contraceptive methods Males must agree to avoid fathering a child and agree to use an appropriate method of contraception Chronic maintenance hemodialysis 3x a week for at least 3 months Chronic maintenance peritoneal dialysis for a minimum of 6 months Kt/V ≥ 1.2 at most recent measurement prior to screening Prescribed and taking at least 3 doses of phosphate binder per day Serum phosphorus levels should be between 4.0 and 8.0 mg/dL at screening Unchanged dose of vitamin D or calcimimetics for the last 4 weeks prior to screening For enrollment in the study after at least 2 weeks of wash-out, subjects must have serum phosphorus levels of at least 6.0 mg/dL but not more than 10.0 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value after 2 or 3 weeks wash-out of phosphate binders Exclusion Criteria: Severe hyperphosphatemia defined as serum phosphorus greater than 10.0 mg/dL on phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening visit Serum/plasma parathyroid hormone >1200 pg/mL Clinical signs of hypovolemia at enrollment History of IBD or IBS-D Scheduled for living donor kidney transplant, change to peritoneal dialysis, home HD or plans to relocate to another center during the study period Positive serology with evidence of significant hepatic impairment or WBC elevation according to the Investigator Life expectancy <6 months Previous exposure to tenapanor

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David P Rosenbaum, PhD

Organizational Affiliation

Ardelyx

Official's Role

Study Director

Facility Information:

Facility Name

Site 529

City

Bronx

State/Province

New York

ZIP/Postal Code

10461

Country

United States

Facility Name

Wake Forest School of Medicine

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

35372979

Citation

Block GA, Bleyer AJ, Silva AL, Weiner DE, Lynn RI, Yang Y, Rosenbaum DP, Chertow GM. Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM). Kidney360. 2021 Aug 27;2(10):1600-1610. doi: 10.34067/KID.0002002021. eCollection 2021 Oct 28.

Results Reference

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A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis

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