A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis

Study Overview
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Brief Summary
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This Phase 3, 26-week, open label study with a 12-week, placebo-controlled, randomized withdrawal period followed by an open label long term safety extension will evaluate the safety and efficacy of tenapanor to treat hyperphosphatemia in end-stage renal disease (ESRD) on hemodialysis and peritoneal dialysis.

Detailed Description
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The study consists of a screening visit, a phosphate binder-free washout period of up to 4 weeks, a 26-week treatment period, an up to 12-week placebo-controlled, randomized withdrawal period, during which patients are randomized 1:1 to either remain on their tenapanor treatment or placebo, followed by an open label safety extension period for a total treatment period of up to 52 weeks. An active control group, for safety analysis only, will receive sevelamer carbonate, open label, for the entire 52-week study period Depending on increase in serum phosphate (s-P) levels, subjects can be randomized 2 or 3 weeks after being taken off their phosphate lowering medication. Subjects who qualify to enroll in the study will be randomized 3:1 to either receive tenapanor at a dose of 30 mg bid or sevelamer carbonate.

Official Title
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A 26-Wk, Phase 3, Open Label (OL) Study With a 12-Wk, Placebo-Controlled, Randomized Withdrawal Period and an OL Safety Extension to Evaluate the Safety and Efficacy of Tenapanor to Treat Hyperphosphatemia in CKD Patients on Dialysis

Conditions
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Hyperphosphatemia

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females must be non-pregnant, non-lactating, and either be post-menopausal for at least 12 months, have documentation of irreversible surgical sterilization, or confirm the use of one of the acceptable contraceptive methods Males must agree to avoid fathering a child and agree to use an appropriate method of contraception Chronic maintenance hemodialysis 3x a week for at least 3 months Chronic maintenance peritoneal dialysis for a minimum of 6 months Kt/V ≥ 1.2 at most recent measurement prior to screening Prescribed and taking at least 3 doses of phosphate binder per day Serum phosphorus levels should be between 4.0 and 8.0 mg/dL at screening Unchanged dose of vitamin D or calcimimetics for the last 4 weeks prior to screening For enrollment in the study after at least 2 weeks of wash-out, subjects must have serum phosphorus levels of at least 6.0 mg/dL but not more than 10.0 mg/dL and have had an increase of at least 1.5 mg/dL versus pre-wash out value after 2 or 3 weeks wash-out of phosphate binders Exclusion Criteria: Severe hyperphosphatemia defined as serum phosphorus greater than 10.0 mg/dL on phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening visit Serum/plasma parathyroid hormone >1200 pg/mL Clinical signs of hypovolemia at enrollment History of IBD or IBS-D Scheduled for living donor kidney transplant, change to peritoneal dialysis, home HD or plans to relocate to another center during the study period Positive serology with evidence of significant hepatic impairment or WBC elevation according to the Investigator Life expectancy <6 months Previous exposure to tenapanor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenapanor 10 mg, 20 mg, 30 mg BID<br>During the 26-week open label part, all enrolled subjects will receive 30 mg BID doses of tenapanor. Investigators may decrease or increase the dose in 10 mg increments to a minimum of 10 g BIDor a maximum of 30 mg BID | Drug: Tenapanor<br>* Active Drug<br>* Other names: RDX5791, AZD1722;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Inactive Drug<br>|
| Active Comparator: Sevelamer Carbonate<br>Subjects randomized into the active control group, for safety analysis, will receive sevelamer carbonate, open label, for the entire 52-week study period. Sevelamer carbonate will be dosed based on package insert instructions (standard of care) | Drug: Sevelamer Carbonate<br>* Active control<br>* Other names: Renvela;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the Responder Population | Patients with at least a 1.2 mg/dL decrease in serum phosphorus during the first 26 weeks of the study were defined as the responder population. | 12 weeks (randomized withdrawal period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the ITT Population | Placebo Adjusted Change in Serum Phosphorus from the beginning to the end of the Randomized Withdrawal Period in all patients | 12 weeks (randomized withdrawal period) | 
| Serum Phosphorus From Baseline | Serum Phosphorus from baseline (post washout) to end of 26 week period | 26 weeks (open label treatment period) |