Ardelyx, Inc.: tenapanor hydrochloride

Drug, and Cosmetic Act for tenapanor hydrochloride 10 mg, 20 mg, and 30 mg tablets.

You also submitted the results of a third trial - a randomized, double-blind, placebo-controlled trial (TEN-02-202), to support use in combination with existing phosphate binder treatment.

In both monotherapy trials, tenapanor's efficacy in reducing serum phosphorus levels was assessed in a randomized, double-blind, placebo-controlled withdrawal period.

In both studies, the primary efficacy analysis during the randomized withdrawal period was to be based on the Efficacy Analysis Set, a subset of the intent-to-treat (ITT) population, which was intended to enrich for a responder population.

Analyses based on the ITT population of the randomized withdrawal periods in Study TEN-02-201 and Study TEN-02-301 provide perhaps the best estimate of the average treatment effect in the subset of patients who are likely to tolerate tenapanor and remain on therapy.

We further note that subgroup analyses and analyses of the distribution of the responses did not suggest a "responder" population with a substantially larger response to treatment.