Clinical trial NCT02675998: An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperphosphatemia
Lead sponsor: Ardelyx
Sponsor class: INDUSTRY
First posted: 2016-02-05
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms
timeFrame: 4 weeks
Secondary outcomes:
measure: Change in Serum Phosphate During 8-Week Treatment Period
timeFrame: Baseline and 8 weeks
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Ardelyx Investigative Site 429
state: Alabama
city: Riverside
country: United States
facility: Ardelyx Investigative Site 425
state: California
city: Denver
country: United States
facility: Ardelyx Clinical Site 403
state: Colorado
city: Lauderdale Lakes
country: United States
facility: Ardelyx Investigative Site 410
state: Florida
city: Miami
country: United States
facility: Ardelyx Investigative Site 430
state: Florida
city: Meridian
country: United States
facility: Ardelyx Investigative Site 427
state: Idaho
city: Shreveport
country: United States
facility: Ardelyx Investigative Site 432
state: Louisiana
city: Bethesda
country: United States
facility: Ardelyx Investigative Site 415
state: Maryland
city: Kalamazoo
country: United States
facility: Ardelyx Investigative Site 402
state: Michigan
city: Roseville
country: United States
facility: Ardelyx Investigative Site 424
state: Michigan
city: Brookhaven
country: United States
facility: Ardelyx Investigative Site 409
state: Mississippi
city: Columbus
country: United States
facility: Ardelyx Investigative Site 417
state: Mississippi
city: Tupelo
country: United States
facility: Ardelyx Investigative Site 431
state: Mississippi
city: Saint Louis
country: United States
facility: Ardelyx Investigative Site 423
state: Missouri
city: Albuquerque
country: United States
facility: Ardelyx Investigative Site 416
state: New Mexico
city: Bronx
country: United States
facility: Ardelyx Investigative Site 419
state: New York
city: Asheville
country: United States
facility: Ardelyx Investigative Site 408
state: North Carolina
city: Charlotte
country: United States
facility: Ardelyx Investigative Site 411
state: North Carolina
city: New Bern
country: United States
facility: Ardelyx Investigative Site 420
state: North Carolina
city: Raleigh
country: United States
facility: Ardelyx Investigative Site 426
state: North Carolina
city: Wilmington
country: United States
facility: Ardelyx Investigative Site 412
state: North Carolina
city: Bethlehem
country: United States
facility: Ardelyx Investigative Site 414
state: Pennsylvania
city: Columbia
country: United States
facility: Ardelyx Investigative Site 404
state: South Carolina
city: Orangeburg
country: United States
facility: Ardelyx Investigative Site 421
state: South Carolina
city: Sumter
country: United States
facility: Ardelyx Investigative Site 428
state: South Carolina
city: Knoxville
country: United States
facility: Ardelyx Investigative Site 413
state: Tennessee
city: Nashville
country: United States
facility: Ardelyx Investigative Site 418
state: Tennessee
city: Austin
country: United States
facility: Ardelyx Investigative Site 406
state: Texas
city: Bellville
country: United States
facility: Ardelyx Investigative Site 405
state: Texas
city: San Antonio
country: United States
facility: Ardelyx Investigative Site 422
state: Texas
city: San Antonio
country: United States
facility: Ardelyx Investigative Site 407
state: Texas
city: Saint George
country: United States
facility: Ardelyx Investigative Site 401
state: Utah
Study officials:
affiliation: Ardelyx, Inc.
name: David P Rosenbaum, Ph.D.
role: STUDY_CHAIR
References: