A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis
A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis
This Phase 3, 26-week, open label study with a 12-week, placebo-controlled, randomized
 withdrawal period followed by an open label long term safety extension will evaluate the
 safety and efficacy of tenapanor to treat hyperphosphatemia in end-stage renal disease (ESRD)
 on hemodialysis and peritoneal dialysis.
The study consists of a screening visit, a phosphate binder-free washout period of up to 4
 weeks, a 26-week treatment period, an up to 12-week placebo-controlled, randomized withdrawal
 period, during which patients are randomized 1:1 to either remain on their tenapanor
 treatment or placebo, followed by an open label safety extension period for a total treatment
 period of up to 52 weeks. An active control group, for safety analysis only, will receive
 sevelamer carbonate, open label, for the entire 52-week study period

 Depending on increase in serum phosphate (s-P) levels, subjects can be randomized 2 or 3
 weeks after being taken off their phosphate lowering medication.

 Subjects who qualify to enroll in the study will be randomized 3:1 to either receive
 tenapanor at a dose of 30 mg bid or sevelamer carbonate.
Inclusion Criteria:

 -  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 a week for at least 3 months

 -  Chronic maintenance peritoneal dialysis for a minimum of 6 months

 -  Kt/V ≥ 1.2 at most recent measurement prior to screening

 -  Prescribed and taking at least 3 doses of phosphate binder per day

 -  Serum phosphorus levels should be between 4.0 and 8.0 mg/dL at screening

 -  Unchanged dose of vitamin D or calcimimetics for the last 4 weeks prior to screening

 -  For enrollment in the study after at least 2 weeks of wash-out, subjects must have
 serum phosphorus levels of at least 6.0 mg/dL but not more than 10.0 mg/dL and have
 had an increase of at least 1.5 mg/dL versus pre-wash out value after 2 or 3 weeks
 wash-out of phosphate binders

 Exclusion Criteria:

 -  Severe hyperphosphatemia defined as serum phosphorus greater than 10.0 mg/dL on
 phosphate-binders at any time point during clinical routine monitoring for the 3
 preceding months before screening visit

 -  Serum/plasma parathyroid hormone >1200 pg/mL

 -  Clinical signs of hypovolemia at enrollment

 -  History of IBD or 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

 -  Positive serology with evidence of significant hepatic impairment or WBC elevation
 according to the Investigator

 -  Life expectancy <6 months

 -  Previous exposure to tenapanor