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

Hyperphosphatemia Clinical Trial

Official title:

An 8-week, Multicenter, Randomized, Double-Blind, Parallel Group Study With a 4-week, Placebo-Controlled, Randomized Withdrawal Period to Evaluate the Efficacy, Safety, and Tolerability of Tenapanor to Treat Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02675998
• Other study ID #: TEN-02-201
• Status: Completed
• Phase: Phase 3
• Start date: January 2016
• Est. completion date: January 17, 2018

Study information

• Verified date: August 2020
• Source: Ardelyx
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 219
• Est. completion date: January 17, 2018
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperphosphatemia
• Kidney Failure, Chronic

Intervention

Drug:
• Tenapanor

• Placebo

Locations

Country	Name	City	State
United States	Ardelyx Investigative Site 416	Albuquerque	New Mexico
United States	Ardelyx Investigative Site 408	Asheville	North Carolina
United States	Ardelyx Investigative Site 406	Austin	Texas
United States	Ardelyx Investigative Site 405	Bellville	Texas
United States	Ardelyx Investigative Site 415	Bethesda	Maryland
United States	Ardelyx Investigative Site 414	Bethlehem	Pennsylvania
United States	Ardelyx Investigative Site 419	Bronx	New York
United States	Ardelyx Investigative Site 409	Brookhaven	Mississippi
United States	Ardelyx Investigative Site 411	Charlotte	North Carolina
United States	Ardelyx Investigative Site 404	Columbia	South Carolina
United States	Ardelyx Investigative Site 417	Columbus	Mississippi
United States	Ardelyx Clinical Site 403	Denver	Colorado
United States	Ardelyx Investigative Site 429	Huntsville	Alabama
United States	Ardelyx Investigative Site 402	Kalamazoo	Michigan
United States	Ardelyx Investigative Site 413	Knoxville	Tennessee
United States	Ardelyx Investigative Site 410	Lauderdale Lakes	Florida
United States	Ardelyx Investigative Site 427	Meridian	Idaho
United States	Ardelyx Investigative Site 430	Miami	Florida
United States	Ardelyx Investigative Site 418	Nashville	Tennessee
United States	Ardelyx Investigative Site 420	New Bern	North Carolina
United States	Ardelyx Investigative Site 421	Orangeburg	South Carolina
United States	Ardelyx Investigative Site 426	Raleigh	North Carolina
United States	Ardelyx Investigative Site 425	Riverside	California
United States	Ardelyx Investigative Site 424	Roseville	Michigan
United States	Ardelyx Investigative Site 401	Saint George	Utah
United States	Ardelyx Investigative Site 423	Saint Louis	Missouri
United States	Ardelyx Investigative Site 407	San Antonio	Texas
United States	Ardelyx Investigative Site 422	San Antonio	Texas
United States	Ardelyx Investigative Site 432	Shreveport	Louisiana
United States	Ardelyx Investigative Site 428	Sumter	South Carolina
United States	Ardelyx Investigative Site 431	Tupelo	Mississippi
United States	Ardelyx Investigative Site 412	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Ardelyx

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms	Serum phosphorus difference between placebo and tenapanor in the change from the end of the 8 week treatment period to the end of the randomized withdrawal period in Efficacy Analysis Set. The efficacy analysis was pre-defined to be a pooled analysis of all tenapanor treated patients with a minimum of a 1.2 mg/dL decrease in serum phosphorus during the 8-week treatment period	4 weeks
Secondary	Change in Serum Phosphate During 8-Week Treatment Period	Serum phosphorus difference between baseline (end of washout period) to the end of the 8 week treatment period in ITT analysis set	Baseline and 8 weeks