An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
- Registration Number
- NCT02675998
- Lead Sponsor
- Ardelyx
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 219
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 3mg BID Tenapanor Tenapanor, 3mg BID (6mg total) Dose Titration Tenapanor 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 Placebo Placebo Placebo 10mg BID Tenapanor Tenapanor, 10mg BID (20mg total)
- Primary Outcome Measures
Name Time Method Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms 4 weeks 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
- Secondary Outcome Measures
Name Time Method Change in Serum Phosphate During 8-Week Treatment Period Baseline and 8 weeks Serum phosphorus difference between baseline (end of washout period) to the end of the 8 week treatment period in ITT analysis set
Trial Locations
- Locations (32)
Ardelyx Investigative Site 409
🇺🇸Brookhaven, Mississippi, United States
Ardelyx Investigative Site 402
🇺🇸Kalamazoo, Michigan, United States
Ardelyx Investigative Site 401
🇺🇸Saint George, Utah, United States
Ardelyx Investigative Site 427
🇺🇸Meridian, Idaho, United States
Ardelyx Investigative Site 413
🇺🇸Knoxville, Tennessee, United States
Ardelyx Investigative Site 430
🇺🇸Miami, Florida, United States
Ardelyx Investigative Site 422
🇺🇸San Antonio, Texas, United States
Ardelyx Investigative Site 407
🇺🇸San Antonio, Texas, United States
Ardelyx Investigative Site 425
🇺🇸Riverside, California, United States
Ardelyx Clinical Site 403
🇺🇸Denver, Colorado, United States
Ardelyx Investigative Site 432
🇺🇸Shreveport, Louisiana, United States
Ardelyx Investigative Site 423
🇺🇸Saint Louis, Missouri, United States
Ardelyx Investigative Site 429
🇺🇸Huntsville, Alabama, United States
Ardelyx Investigative Site 410
🇺🇸Lauderdale Lakes, Florida, United States
Ardelyx Investigative Site 412
🇺🇸Wilmington, North Carolina, United States
Ardelyx Investigative Site 417
🇺🇸Columbus, Mississippi, United States
Ardelyx Investigative Site 408
🇺🇸Asheville, North Carolina, United States
Ardelyx Investigative Site 424
🇺🇸Roseville, Michigan, United States
Ardelyx Investigative Site 431
🇺🇸Tupelo, Mississippi, United States
Ardelyx Investigative Site 428
🇺🇸Sumter, South Carolina, United States
Ardelyx Investigative Site 426
🇺🇸Raleigh, North Carolina, United States
Ardelyx Investigative Site 404
🇺🇸Columbia, South Carolina, United States
Ardelyx Investigative Site 418
🇺🇸Nashville, Tennessee, United States
Ardelyx Investigative Site 415
🇺🇸Bethesda, Maryland, United States
Ardelyx Investigative Site 416
🇺🇸Albuquerque, New Mexico, United States
Ardelyx Investigative Site 414
🇺🇸Bethlehem, Pennsylvania, United States
Ardelyx Investigative Site 406
🇺🇸Austin, Texas, United States
Ardelyx Investigative Site 419
🇺🇸Bronx, New York, United States
Ardelyx Investigative Site 421
🇺🇸Orangeburg, South 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 405
🇺🇸Bellville, Texas, United States