A Long-Term Study of Tenapanor Alone or in Combination With Sevelamer in Patients With CKD on Dialysis and HP

Study Overview
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Brief Summary
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The study is designed to evaluate the ability of tenapanor alone or in combination with sevelamer to achieve serum phosphorus concentration (sP) within the population reference range (sP >2.5 and ≤4.5 mg/dL) in patients with end-stage renal disease (ESRD) on dialysis with hyperphosphatemia (>4.5 mg/dL).

Detailed Description
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Patients who complete the TEN-02-301 study (PHREEDOM) may be eligible to enroll into TEN-02-401 (NORMALIZE). Patients from the TEN-02-301 tenapanor arm will either receive only tenapanor or be given sevelamer in addition to tenapanor based on their sP. Patients from the TEN-02-301 sevelamer arm will be given tenapanor in addition to their sevelamer dose and the sevelamer dose will then be adjusted based on their sP following a protocol-specified dose titration schedule. Patients will be monitored for safety and efficacy with in-office and telephone visits for up to an additional 18 months. Laboratory assessments will be measured at every visit (Weeks 1, 2, 3, 4, 6 and 8 and Months 3, 6, 9, 12, 15 and 18) using a central laboratory. Safety assessments will be performed during the study and will include physical examinations, vital signs (blood pressure and pulse), body weights, clinical laboratory evaluations, 12-lead electrocardiograms (ECGs), and adverse event (AE) monitoring.

Official Title
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A Long-Term, Open Label Study to Evaluate the Ability of Tenapanor Alone or in Combination With Sevelamer to Treat to Goal Serum Phosphorus in Patients With End-Stage Kidney Disease on Dialysis (NORMALIZE)

Conditions
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Hyperphosphatemia, End Stage Renal Disease

Intervention / Treatment
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* Drug: Tenapanor
* Drug: Sevelamer Carbonate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must complete TEN-02-301 (PHREEDOM) Exclusion Criteria: Schedlued for kidney transplant Life expectancy <12 months
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenapanor w/Sevelamer<br>Tenapanor will be administered QD or BID and sevelamer can be added to achieve desired serum phosphorus level | Drug: Tenapanor<br>* NHE3 Inhibitor<br>Drug: Sevelamer Carbonate<br>* Phosphate binder<br>|
| Experimental: Sevelamer w/Tenapanor<br>Sevelamer will be administered QD, BID or TID and tenapanor will be added to achieve desired serum phosphorus level and sevelamer dose will be decreased as needed | Drug: Tenapanor<br>* NHE3 Inhibitor<br>Drug: Sevelamer Carbonate<br>* Phosphate binder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achieving Normal Serum Phosphorus Level | Proportion of patients with serum phosphorus between 2.5 and 4.5 mg/dL | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Phosphorus (s-P) From TEN-02-301 (Parent Study) Baseline | The change from the baseline s-P from the parent study until the endpoint visit which was up to 2.5 years after the baseline | up to 2.5 years | 
| Change From Baseline in Serum Phosphorus (of Extension Study; TEN-02-401) to Endpoint Visit | Baseline upon enrollment in the 18-month long-term extension study | up to 18 months |