An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)

NCT ID: NCT02675998

Last Updated: 2020-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2018-01-17

Brief Summary

This phase 3, 8-week, randomized, double-blind, parallel group, multi-center study with a 4-week, placebo-controlled, randomized withdrawal period will evaluate the efficacy, safety and tolerability of Tenapanor to treat hyperphosphatemia in end-stage renal disease patients on hemodialysis (ESRD-HD). Subjects who qualify are randomized into the study will either receive 3 mg BID, 10 mg BID, or a titration regimen of tenapanor.

Detailed Description

The study consists of a screening visit, a wash out period of up to 3 weeks, when existing phosphate lowering medication is withheld, an 8-week treatment period, in which all groups receive tenapanor, and a 4-week placebo-controlled, randomized withdrawal period, during which patients are re-randomized 1:1 to either remain on their current tenapanor treatment or placebo.

Depending on the increase in serum phosphate levels, subjects can be randomized 1,2, or 3 weeks after being taken off their phosphate lowering medication.

Conditions

Hyperphosphatemia

Study Design

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

Study Groups

3mg BID

Tenapanor, 3mg BID (6mg total)

Group Type: EXPERIMENTAL

Tenapanor

Intervention Type: DRUG

10mg BID

Tenapanor, 10mg BID (20mg total)

Group Type: EXPERIMENTAL

Tenapanor

Intervention Type: DRUG

Dose Titration

Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question

Group Type: EXPERIMENTAL

Tenapanor

Intervention Type: DRUG

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Tenapanor

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

RDX5791, AZD1722

Eligibility Criteria

Inclusion Criteria

• 18 to 80 years old
• 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/week for at least 3 months
• Kt/V ≥ 1.3 at most recent measurement prior to screening
• Prescribed and taking at least 3 doses of phosphate binder per day
• Serum phosphate levels should be between 4.0 and 7.0 mg/dL (inclusive) at screening
• For randomization in the study, after 1 week wash-out of phosphate binders, subjects must have serum phosphate level of at least 9 mg/dL but below 10 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value
• For randomization in the study, after 2 or 3 weeks wash-out of phosphate binders, subjects must have serum phosphate level of at least 6 mg/dL but below 10 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value

Exclusion Criteria

• Severe hyperphosphatemia defined as >10 mg/dL on Phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening
• Serum parathyroid hormone >1200 pg/mL
• Persistent metabolic acidosis defined as serum carbon dioxide <18 mmol/L from two consecutive measurements during screening and washout periods
• Clinical signs of hypovolemia at randomization
• History of inflammatory bowel disease (IBD) or diarrhea predominant irritable bowel syndrome (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
• Diarrhea or loose stools during the week before randomization defined as BSFS ≥ 6 and frequency ≥ 3 for 2 or more days
• Any evidence of or treatment of malignancy within one year, excluding non-melanomatous malignancies of the skin
• Positive serology with evidence of significant hepatic impairment or WBC elevation according to the Investigator
• Life expectancy < 6 months

• 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, Ph.D.

Role: STUDY_CHAIR

Ardelyx, Inc.

Locations

Ardelyx Investigative Site 429

Huntsville, Alabama, United States

Ardelyx Investigative Site 425

Riverside, California, United States

Ardelyx Clinical Site 403

Denver, Colorado, United States

Ardelyx Investigative Site 410

Lauderdale Lakes, Florida, United States

Ardelyx Investigative Site 430

Miami, Florida, United States

Ardelyx Investigative Site 427

Meridian, Idaho, United States

Ardelyx Investigative Site 432

Shreveport, Louisiana, United States

Ardelyx Investigative Site 415

Bethesda, Maryland, United States

Ardelyx Investigative Site 402

Kalamazoo, Michigan, United States

Ardelyx Investigative Site 424

Roseville, Michigan, United States

Ardelyx Investigative Site 409

Brookhaven, Mississippi, United States

Ardelyx Investigative Site 417

Columbus, Mississippi, United States

Ardelyx Investigative Site 431

Tupelo, Mississippi, United States

Ardelyx Investigative Site 423

St Louis, Missouri, United States

Ardelyx Investigative Site 416

Albuquerque, New Mexico, United States

Ardelyx Investigative Site 419

The Bronx, New York, United States

Ardelyx Investigative Site 408

Asheville, North Carolina, United States

Ardelyx Investigative Site 411

Charlotte, North Carolina, United States

Ardelyx Investigative Site 420

New Bern, North Carolina, United States

Ardelyx Investigative Site 426

Raleigh, North Carolina, United States

Ardelyx Investigative Site 412

Wilmington, North Carolina, United States

Ardelyx Investigative Site 414

Bethlehem, Pennsylvania, United States

Ardelyx Investigative Site 404

Columbia, South Carolina, United States

Ardelyx Investigative Site 421

Orangeburg, South Carolina, United States

Ardelyx Investigative Site 428

Sumter, South Carolina, United States

Ardelyx Investigative Site 413

Knoxville, Tennessee, United States

Ardelyx Investigative Site 418

Nashville, Tennessee, United States

Ardelyx Investigative Site 406

Austin, Texas, United States

Ardelyx Investigative Site 405

Bellville, Texas, United States

Ardelyx Investigative Site 422

San Antonio, Texas, United States

Ardelyx Investigative Site 407

San Antonio, Texas, United States

Ardelyx Investigative Site 401

St. George, Utah, 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)

Silva AL, Chertow GM, Hernandez GT, Lynn RI, Tietjen DP, Rosenbaum DP, Yang Y, Edelstein S. Tenapanor Improves Long-Term Control of Hyperphosphatemia in Patients Receiving Maintenance Dialysis: the NORMALIZE Study. Kidney360. 2023 Nov 1;4(11):1580-1589. doi: 10.34067/KID.0000000000000280. Epub 2023 Oct 19.

Reference Type: DERIVED

PMID: 37853560 (View on PubMed)

Other Identifiers

TEN-02-201

Identifier Type: -

Identifier Source: org_study_id