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

NCT ID: NCT03824587

Last Updated: 2023-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 236 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-28
• Study Completion Date: 2019-07-17

Brief Summary

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.

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

Conditions

Hyperphosphatemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Tenapanor

Intervention Type: DRUG

Active Drug

Phosphate Binder Agents

Intervention Type: DRUG

standard of care phosphate binder use at study entry was maintained throughout the entire study

Placebo

same size, weight and appearance of experimental drug

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Inactive Drug

Phosphate Binder Agents

Intervention Type: DRUG

standard of care phosphate binder use at study entry was maintained throughout the entire study

Interventions

Tenapanor

Active Drug

Intervention Type: DRUG

Placebo

Inactive Drug

Intervention Type: DRUG

Phosphate Binder Agents

standard of care phosphate binder use at study entry was maintained throughout the entire study

Intervention Type: DRUG

Other Intervention Names

sevelamer carbonate; ferric citrate; calcium carbonate; calcium acetate; sucroferric oxyhydroxide

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ardelyx

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David P Rosenbaum, PhD

Role: STUDY_CHAIR

Ardelyx

Locations

Nephrology Consultants, LLC

Huntsville, Alabama, United States

US Renal Care Pine Bluff

Pine Bluff, Arkansas, United States

Southeast Renal Research

Beverly Hills, California, United States

California Institute of Renal Research - Chula Vista

Chula Vista, California, United States

North America Research Institute

Lynwood, California, United States

DaVita Clinical Research - Santa Fe Spring

Montebello, California, United States

Central Coast Nephrology

Salinas, California, United States

North America Research Institute - San Dimas

San Dimas, California, United States

Chabot Nephrology Medical Group

Union City, California, United States

American Institute of Research

Whittier, California, United States

Nova Clinical Research, LLC

Bradenton, Florida, United States

Horizon Research Group - Coral Gables

Coral Gables, Florida, United States

South Florida Research Institute

Lauderdale Lakes, Florida, United States

Total Research Group, LLC

Miami, Florida, United States

Omega Research Consultants, LLC

Orlando, Florida, United States

Genesis Clinical Trials

Tampa, Florida, United States

Dialysis Clinic, Inc - Albany GA

Albany, Georgia, United States

Boise Kidney & Hypertension, PLLC - Meridian

Caldwell, Idaho, United States

Renal Associates of Baton Rouge

Baton Rouge, Louisiana, United States

Dialysis Clinic, Inc - Boston/Somerville

Boston, Massachusetts, United States

Paragon Health PC - Nephrology Center

Kalamazoo, Michigan, United States

InterMed Consultants

Minneapolis, Minnesota, United States

Nephrology and Hypertension Associates, LTD

Tupelo, Mississippi, United States

Clinical Research Consultants, LLC

Kansas City, Missouri, United States

Dialysis Clinic, Inc - Kansas City

Kansas City, Missouri, United States

Polack Renal, LLC (SMO)

St Louis, Missouri, United States

Kidney Specialists of Southern Nevada

Las Vegas, Nevada, United States

Sierra Nevada Nephrology Consultants

Reno, Nevada, United States

Dialysis Clinic, Inc - North Brunswick

North Brunswick, New Jersey, United States

Renal Medicine Associates

Albuquerque, New Mexico, United States

U.S. Renal Care - Gallup

Gallup, New Mexico, United States

Northwell Health

Great Neck, New York, United States

Mountain Kidney and Hypertension Associates

Asheville, North Carolina, United States

Mountain Kidney & Hypertension Associates, P.A.

Asheville, North Carolina, United States

Durham Nephrology Associates

Durham, North Carolina, United States

Southeastern Nephrology Associates - Wilmington

Wilmington, North Carolina, United States

University of Cincinnati (UC) - Department of Nephrology

Cincinnati, Ohio, United States

Northeast Clinical Research Center

Bethlehem, Pennsylvania, United States

Columbia Nephrology Associates, P.A.

Columbia, South Carolina, United States

South Carolina Nephrology & Hypertension Center Inc.

Orangeburg, South Carolina, United States

DCI - Spartanburg

Spartanburg, South Carolina, United States

Knoxville Kidney Center, PLLC

Knoxville, Tennessee, United States

Med Center Dialysis

Houston, Texas, United States

US Renal Care - Waxahachie

Mansfield, Texas, United States

US Renal Care - Mesquite

Mesquite, Texas, United States

Clinical Advancement Center, PLLC

San Antonio, Texas, United States

US Renal Care - Pleasanton Road

San Antonio, Texas, United States

US Renal Care - Westover Hills

San Antonio, Texas, United States

Countries

United States

References

Sprague SM, Weiner DE, Tietjen DP, Pergola PE, Fishbane S, Block GA, Silva AL, Fadem SZ, Lynn RI, Fadda G, Pagliaro L, Zhao S, Edelstein S, Spiegel DM, Rosenbaum DP. Tenapanor as Therapy for Hyperphosphatemia in Maintenance Dialysis Patients: Results from the OPTIMIZE Study. Kidney360. 2024 May 1;5(5):732-742. doi: 10.34067/KID.0000000000000387. Epub 2024 Feb 7.

Reference Type: DERIVED

PMID: 38323855 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33766811 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

TEN-02-202

Identifier Type: -

Identifier Source: org_study_id