A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Tenapanor 10 mg, 20 mg, 30 mg BID 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
Active Drug
Other Names:
|
| Placebo Comparator: Placebo Placebo |
Drug: Placebo
Inactive Drug
|
| Active Comparator: Sevelamer Carbonate 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
Active control
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in serum phosphorus levels during placebo controlled randomized withdrawal period in the responder population [12 weeks (randomized withdrawal period)]
Placebo adjusted change in serum phosphorus from the beginning to the end of the randomized withdrawal period in patients with at least a 1.2 mg/dL decrease in serum phosphorus (responder population) during the first 26 weeks of the study
Secondary Outcome Measures
- Change in serum phosphorus levels during placebo controlled randomized withdrawal period in the ITT Population [12 weeks (randomized withdrawal period)]
Placebo Adjusted Change in Serum Phosphorus from the beginning to the end of the Randomized Withdrawal Period in all patients
- Change in serum phosphorus from Baseline [26 weeks (open label treatment period)]
change from baseline (post washout) to end of 26 week period
- Effect of Tenapanor on serum FGF23 levels [52 weeks]
Change from baseline to end of different treatment periods
Eligibility Criteria
Criteria
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
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Chronic maintenance hemodialysis 3x a week for at least 3 months
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Chronic maintenance peritoneal dialysis for a minimum of 6 months
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Kt/V ≥ 1.2 at most recent measurement prior to screening
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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
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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
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History of IBD or IBS-D
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site 529 | Bronx | New York | United States | 10461 |
| 2 | Wake Forest School of Medicine | Winston-Salem | North Carolina | United States | 27157 |
Sponsors and Collaborators
- Ardelyx
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TEN-02-301