Study to Evaluate the Use of Tenapanor as Core Therapy in the Treatment of Hyperphosphatemia

Randomized Open-Label Study to Evaluate Tenapanor as the Core Therapy in the Treatment of Hyperphosphatemia in Patients With Chronic Kidney Disease Who Are Phosphate Binder Naive or on Phosphate Binders to Optimize Phosphorus Management

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.

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.

Inclusion Criteria:

1. Signed and dated informed consent form prior to any study specific procedures.
2. Males or females aged 18 to 80 years, inclusive, at Screening (Visit 1).
3. Females must be non-pregnant and non-lactating.
4. Patients on phosphate binder therapy must be on chronic maintenance hemodialysis (HD) 3 times per week for at least 3 months or chronic maintenance peritoneal dialysis (PD) for a minimum of 6 months. If modality of dialysis has changed, the patient must meet one of the two dialysis criteria above and been on the new modality of dialysis for a minimum of one month. Phosphate binder naïve patients must be on chronic maintenance HD 3 times per week or chronic maintenance PD.
5. Kt/V ≥1.2 at most recent measurement prior to Screening (Visit 1).
6. Prescribed and taking phosphate binder medication at least 3 times per day or being phosphate binder naïve; defined as having not taken phosphate binders for at least 3 months prior to Screening. The patient must be taking a minimum of 6 pills per day for Renvela, Auryxia, or PhosLo; and/or a minimum of 3 pills per day for Fosrenol or Velphoro.
7. For patients taking phosphate binders, both the s-P level at the most recent measurement prior to Screening (Visit 1) and the s-P level at Screening (Visit 1) must be >5.5 and ≤10.0 mg/dL.
8. For phosphate binder naïve patients, the s-P level at Screening (Visit 1) must be >4.5 and ≤10.0 mg/dL.
9. Able to understand and comply with the protocol.

Exclusion Criteria:

1. Severe hyperphosphatemia defined as having an s-P level >10.0 mg/dL at any time point during routine clinical monitoring for the 3 preceding months before Screening (Visit 1).
2. Serum/plasma PTH >1200 pg/mL. The most recent value from the patient's medical records should be used.
3. Clinical signs of hypovolemia at Screening (Visit 1) as judged by the Investigator.
4. History of inflammatory bowel disease or irritable bowel syndrome with diarrhea.
5. Scheduled for living donor kidney transplant or plans to relocate to another center during the study.
6. Use of an investigational agent within 30 days prior to Screening (Visit 1).
7. 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).
8. If, in the opinion of the Investigator, the patient is unable or unwilling to fulfill the requirements of the protocol or has a condition which would render the results uninterpretable.