Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy
Study to Evaluate the Efficacy of Tenapanor as Adjunctive Therapy to Phosphate Binder Therapy
This is a randomized, double-blind, placebo-controlled study to evaluate the effect of
 tenapanor on change in s-P levels when tenapanor is administered orally, twice daily for 28
 days as adjunctive therapy to ESRD subjects with hyperphosphatemia on stable phosphate binder
 therapy.
The study consists of a Screening visit; a Run-in Period of at least 2 weeks and up to 4
 weeks, where existing phosphate binder treatment is maintained; and a 4-week Double-Blind
 Treatment Period.

 At Screening, a subject must be on thrice daily phosphate binder therapy and have a serum
 phosphate (s-P) level ≥5.5 and ≤10.0 mg/dL to qualify for entering the study. s-P will be
 measured at each visit during the run-in period to enable the evaluation of the s-P
 randomization criteria.

 Subjects who qualify to enroll in the study will be randomized in a 1:1 ratio to receive
 tenapanor or placebo while continuing their existing phosphate binder treatment.

 During the Double-Blind Treatment Period, subjects will receive tenapanor or placebo starting
 at a dose of 30 mg bid
Inclusion Criteria:

 -  Signed and dated informed consent prior to any study specific procedures.

 -  Males or females aged 18 to 80 years, inclusive, at Screening

 -  Females must be non-pregnant, non-lactating and either be post-menopausal for at least
 -2 months, have documentation of irreversible surgical sterilization, use of
 acceptable -contraceptive method, or sexual abstinence, or a sterile sexual partner
 from Screening -until 30 days after the last subject visit.

 -  Males must agree to avoid fathering a child (or donating sperm), and therefore be
 either sterile (documented) or agree to use approved methods of contraception, from
 the time of enrollment until 30 days after end of study.

 -  Chronic maintenance hemodialysis (HD) 3x/week for at least 3 months or chronic
 maintenance peritoneal dialysis (PD) for a minimum of 6 months.

 -  If receiving active vitamin D or calcimimetics, the dose should have been unchanged
 for the last 4 weeks prior to Screening.

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

 -  Prescribed and taking phosphate binder medication at least 3 times per day, and the
 prescribed dose should have been unchanged during the last 4 weeks prior to Screening.

 -  Serum phosphorus levels must be ≥5.5 and ≤10.0 mg/dL at Screening and the end of the
 run-in period, analyzed at the central laboratory used in the study.

 Exclusion Criteria:

 -  Severe hyperphosphatemia defined as having an s-P level >10.0 mg/dL on
 phosphate-binders at any time point during routine clinical monitoring for the 3
 preceding months before Screening.

 -  Serum/plasma parathyroid hormone >1200 pg/mL.

 -  Clinical signs of hypovolemia at Screening as judged by the Investigator.

 -  History of inflammatory bowel disease (IBD) or irritable bowel syndrome with diarrhea
 (IBS-D).

 -  Scheduled for living donor kidney transplant or plans to relocate to another center
 during the study period.

 -  Use of an investigational agent within 30 days prior to Screening.

 -  Involvement in the planning and/or conduct of the study (applies to both
 Ardelyx/Contract Research Organization (CRO) staff and/or staff at the study site).

 -  If, in the opinion of the Investigator, the subject is unable or unwilling to fulfill
 the requirements of the protocol or has a condition which would render the results
 uninterpretable.