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