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

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

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.

Study Overview

• Status: Completed
• Conditions: Hyperphosphatemia
• Intervention / Treatment: Drug: Tenapanor; Drug: Placebo; Drug: Sevelamer Carbonate

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.

• Study Type: Interventional
• Enrollment (Actual): 1559
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Site 529
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Inactive Drug
Experimental: Tenapanor 10 mg, 20 mg, 30 mg BID; 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	Drug: Tenapanor; Active Drug; Other Names: RDX5791, AZD1722
Active Comparator: Sevelamer Carbonate; 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)	Drug: Sevelamer Carbonate; Active control; Other Names: Renvela

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	12 weeks (randomized withdrawal period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	12 weeks (randomized withdrawal period)
Serum Phosphorus From Baseline	Serum Phosphorus from baseline (post washout) to end of 26 week period	26 weeks (open label treatment period)

Collaborators and Investigators

• Sponsor: Ardelyx
• Investigators: Study Director: David P Rosenbaum, PhD, Ardelyx

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 8, 2018
• Primary Completion (Actual): November 15, 2019
• Study Completion (Actual): February 27, 2020

Study Registration Dates

• First Submitted: January 19, 2018
• First Submitted That Met QC Criteria: February 2, 2018
• First Posted (Actual): February 9, 2018

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 8, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Phosphorus Metabolism Disorders; Hyperphosphatemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Sevelamer
• Other Study ID Numbers: TEN-02-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No