Study to Evaluate the Use of Tenapanor as Core Therapy in the Treatment of Hyperphosphatemia
Condition: Chronic Kidney Disease Requiring Chronic Dialysis; Hyperphosphatemia
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hyperphosphatemia
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a randomized, open-label study to evaluate different methods of initiating tenapanor
      therapy in CKD patients on dialysis with hyperphosphatemia, when they are either phosphate
      binder naïve or on phosphate binder therapy. The objective to evaluate the effect of
      tenapanor alone or in combination with phosphate binders to achieve target serum phosphorus
      (s-P) levels of ≤5.5 mg/dL when tenapanor is administered as the core therapy (alone or in
      combination with phosphate binders) for the treatment of hyperphosphatemia in patients with
      chronic kidney disease (CKD) on dialysis.
    

Detailed description: 
      Approximately 330 CKD patients on dialysis with hyperphosphatemia (>4.5 mg/dL) will be
      enrolled in this study.

      This is a randomized, open-label study to evaluate different methods of initiating tenapanor
      therapy in CKD patients on dialysis with hyperphosphatemia, when they are either phosphate
      binder naïve or on phosphate binder therapy.

      The study consists of a Screening visit and a 10-week open-label Treatment Period (TP), for
      which

        -  Patients with s-P >5.5 and ≤10.0 mg/dL under stable phosphate binder treatment are
           randomized in a 1:1 ratio to two different treatment cohorts:

             -  Cohort 1 (straight switch), which stops taking phosphate binders and is started on
                tenapanor 30 mg twice daily (BID) at Visit 2 (Day 1);

             -  Cohort 2, which decreases phosphate binder dose by at least 50% (may be more than
                50% if patient is taking an odd number of binder pills each day), with ability to
                switch the binder regimen from thrice daily (TID) to BID or QD; and initiates
                tenapanor 30 mg BID at Visit 2 (Day 1).

        -  Phosphate binder naïve patients with s-P >4.5 and ≤10.0 mg/dL are enrolled as Cohort 3
           and receive tenapanor at Visit 2 (Day 1) with a starting dose of 30 mg BID.

        -  Patients on phosphate binder therapy must receive phosphate binder(s) thrice daily, and
           both the s-P level assessed at the most recent measurement prior to the Screening visit
           (Visit 1) and the s-P level assessed at the Screening visit (Visit 1) must be >5.5 and
           ≤10.0 mg/dL to qualify for randomization into Cohort 1 or Cohort 2 at Visit 2 (Day 1).

        -  Phosphate binder naïve patients must have the s-P level assessed at the Screening visit
           (Visit 1) >4.5 and ≤10.0 mg/dL to qualify for enrollment into Cohort 3 at Visit 2 (Day
           1).

      Patients who do not meet the randomization/enrollment criteria on s-P will be discontinued as
      screen failures.

      During the TP, patients will receive tenapanor starting at a dose of 30 mg twice daily.
      Tenapanor will be taken twice daily; just prior to breakfast and dinner. The Investigator may
      titrate the dose of tenapanor in 10 mg increments down to a minimum of 10 mg QD or up to a
      maximum of 30 mg BID at any time during the study based on s-P levels and/or gastrointestinal
      (GI) tolerability.
    

Intervention name(s): Tenapanor
Intervention type(s): Drug
Intervention description(s): Use of tenapanor
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hyperphosphatemia