Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy

A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy in End-Stage Renal Disease (ESRD) Subjects With Hyperphosphatemia

This is a randomized, double-blind, placebo-controlled study to evaluate the effect of tenapanor on change in s-P levels when tenapanor is administered orally, twice daily for 28 days as adjunctive therapy to ESRD subjects with hyperphosphatemia on stable phosphate binder therapy.

Study Overview

• Status: Completed
• Conditions: Hyperphosphatemia
• Intervention / Treatment: Drug: Tenapanor; Drug: Placebo; Drug: Phosphate Binder Agents

Detailed Description

The study consists of a Screening visit; a Run-in Period of at least 2 weeks and up to 4 weeks, where existing phosphate binder treatment is maintained; and a 4-week Double-Blind Treatment Period.

At Screening, a subject must be on thrice daily phosphate binder therapy and have a serum phosphate (s-P) level ≥5.5 and ≤10.0 mg/dL to qualify for entering the study. s-P will be measured at each visit during the run-in period to enable the evaluation of the s-P randomization criteria.

Subjects who qualify to enroll in the study will be randomized in a 1:1 ratio to receive tenapanor or placebo while continuing their existing phosphate binder treatment.

During the Double-Blind Treatment Period, subjects will receive tenapanor or placebo starting at a dose of 30 mg bid

• Study Type: Interventional
• Enrollment (Actual): 236
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Nephrology Consultants, LLC
  • Arkansas
    • Pine Bluff, Arkansas, United States, 71603
      • US Renal Care Pine Bluff
  • California
    • Beverly Hills, California, United States, 90211
      • Southeast Renal Research
    • Chula Vista, California, United States, 91910
      • California Institute of Renal Research - Chula Vista
    • Lynwood, California, United States, 90262
      • North America Research Institute
    • Montebello, California, United States, 90640
      • DaVita Clinical Research - Santa Fe Spring
    • Salinas, California, United States, 93901
      • Central Coast Nephrology
    • San Dimas, California, United States, 91773
      • North America Research Institute - San Dimas
    • Union City, California, United States, 94587
      • Chabot Nephrology Medical Group
    • Whittier, California, United States, 90603
      • American Institute of Research
  • Florida
    • Bradenton, Florida, United States, 34209
      • Nova Clinical Research, LLC
    • Coral Gables, Florida, United States, 33134
      • Horizon Research Group - Coral Gables
    • Lauderdale Lakes, Florida, United States, 33313
      • South Florida Research Institute
    • Miami, Florida, United States, 33126
      • Total Research Group, LLC
    • Orlando, Florida, United States, 32810
      • Omega Research Consultants, LLC
    • Tampa, Florida, United States, 33614
      • Genesis Clinical Trials
  • Georgia
    • Albany, Georgia, United States, 31701
      • Dialysis Clinic, Inc - Albany GA
  • Idaho
    • Caldwell, Idaho, United States, 83605
      • Boise Kidney & Hypertension, PLLC - Meridian
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Renal Associates of Baton Rouge
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Dialysis Clinic, Inc - Boston/Somerville
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Paragon Health PC - Nephrology Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • InterMed Consultants
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Nephrology and Hypertension Associates, LTD
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Clinical Research Consultants, LLC
    • Kansas City, Missouri, United States, 64131
      • Dialysis Clinic, Inc - Kansas City
    • Saint Louis, Missouri, United States, 63121
      • Polack Renal, LLC (SMO)
  • Nevada
    • Las Vegas, Nevada, United States, 89107
      • Kidney Specialists of Southern Nevada
    • Reno, Nevada, United States, 89511
      • Sierra Nevada Nephrology Consultants
  • New Jersey
    • North Brunswick, New Jersey, United States, 08902
      • Dialysis Clinic, Inc - North Brunswick
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Renal Medicine Associates
    • Gallup, New Mexico, United States, 87301
      • U.S. Renal Care - Gallup
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Kidney and Hypertension Associates
    • Asheville, North Carolina, United States, 28805
      • Mountain Kidney & Hypertension Associates, P.A.
    • Durham, North Carolina, United States, 27704
      • Durham Nephrology Associates
    • Wilmington, North Carolina, United States, 28401
      • Southeastern Nephrology Associates - Wilmington
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati (UC) - Department of Nephrology
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • Northeast Clinical Research Center
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Columbia Nephrology Associates, P.A.
    • Orangeburg, South Carolina, United States, 29118
      • South Carolina Nephrology & Hypertension Center Inc.
    • Spartanburg, South Carolina, United States, 29301
      • DCI - Spartanburg
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center, PLLC
  • Texas
    • Houston, Texas, United States, 77004
      • Med Center Dialysis
    • Mansfield, Texas, United States, 76063
      • US Renal Care - Waxahachie
    • Mesquite, Texas, United States, 75150
      • US Renal Care - Mesquite
    • San Antonio, Texas, United States, 78212
      • Clinical Advancement Center, PLLC
    • San Antonio, Texas, United States, 78221
      • US Renal Care - Pleasanton Road
    • San Antonio, Texas, United States, 78251
      • US Renal Care - Westover Hills

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed and dated informed consent prior to any study specific procedures.
• Males or females aged 18 to 80 years, inclusive, at Screening
• Females must be non-pregnant, non-lactating and either be post-menopausal for at least -2 months, have documentation of irreversible surgical sterilization, use of acceptable -contraceptive method, or sexual abstinence, or a sterile sexual partner from Screening -until 30 days after the last subject visit.
• Males must agree to avoid fathering a child (or donating sperm), and therefore be either sterile (documented) or agree to use approved methods of contraception, from the time of enrollment until 30 days after end of study.
• Chronic maintenance hemodialysis (HD) 3x/week for at least 3 months or chronic maintenance peritoneal dialysis (PD) for a minimum of 6 months.
• If receiving active vitamin D or calcimimetics, the dose should have been unchanged for the last 4 weeks prior to Screening.
• Kt/V ≥1.2 at most recent measurement prior to Screening.
• Prescribed and taking phosphate binder medication at least 3 times per day, and the prescribed dose should have been unchanged during the last 4 weeks prior to Screening.
• Serum phosphorus levels must be ≥5.5 and ≤10.0 mg/dL at Screening and the end of the run-in period, analyzed at the central laboratory used in the study.

Exclusion Criteria:

• Severe hyperphosphatemia defined as having an s-P level >10.0 mg/dL on phosphate-binders at any time point during routine clinical monitoring for the 3 preceding months before Screening.
• Serum/plasma parathyroid hormone >1200 pg/mL.
• Clinical signs of hypovolemia at Screening as judged by the Investigator.
• History of inflammatory bowel disease (IBD) or irritable bowel syndrome with diarrhea (IBS-D).
• Scheduled for living donor kidney transplant or plans to relocate to another center during the study period.
• Use of an investigational agent within 30 days prior to Screening.
• Involvement in the planning and/or conduct of the study (applies to both Ardelyx/Contract Research Organization (CRO) staff and/or staff at the study site).
• If, in the opinion of the Investigator, the subject is unable or unwilling to fulfill the requirements of the protocol or has a condition which would render the results uninterpretable.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tenapanor 30 mg BID; During the Double-Blind Treatment Period, subjects will receive tenapanor starting at a dose of 30 mg bid (three 10 mg tablets each time). Investigators may decrease or increase the dose of study medication based on s-P levels and/or gastrointestinal (GI) tolerability in 10 mg increments to a minimum of 10 mg bid or a maximum of 30 mg bid at any time during the Double-Blind Treatment Period.	Drug: Tenapanor; Active Drug; Drug: Phosphate Binder Agents; standard of care phosphate binder use at study entry was maintained throughout the entire study; Other Names: calcium carbonate; calcium acetate; sevelamer carbonate; ferric citrate; sucroferric oxyhydroxide
Placebo Comparator: Placebo; same size, weight and appearance of experimental drug	Drug: Placebo; Inactive Drug; Drug: Phosphate Binder Agents; standard of care phosphate binder use at study entry was maintained throughout the entire study; Other Names: calcium carbonate; calcium acetate; sevelamer carbonate; ferric citrate; sucroferric oxyhydroxide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Phosphorus (s-P) Level From Baseline to Week 4.	Difference in mean change from baseline in s-P level at Week 4 between the tenapanor and placebo groups.	4 Weeks (28 days randomization period; from baseline to week 4)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
s-P Response at Week 4	Achieving an s-P level <5.5 mg/dL	4 Weeks (28 days randomization period)
Relative Change From Baseline in iFGF23 at Week 4	iFGF23 at Week 4/baseline iFGF23 - 1	4 Weeks (28 days randomization period)
Relative Change From Baseline in cFGF23 at Week 4	cFGF23 at Week 4/baseline cFGF23 - 1	4 Weeks (28 days randomization period)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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 Jun 1;32(6):1465-1473. doi: 10.1681/ASN.2020101398. Epub 2021 Mar 25.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2019
• Primary Completion (Actual): July 17, 2019
• Study Completion (Actual): July 17, 2019

Study Registration Dates

• First Submitted: January 29, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 31, 2019

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: February 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Phosphorus Metabolism Disorders; Hyperphosphatemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Chelating Agents; Sequestering Agents; Antacids; Calcium; Sevelamer; Calcium, Dietary; Calcium Carbonate; Calcium acetate
• Other Study ID Numbers: TEN-02-202

Drug and device information, study documents

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