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

Phase 3

Completed

• Conditions: Hyperphosphatemia
• Interventions: Drug: Placebo; Drug: Tenapanor; Drug: Sevelamer Carbonate

• Registration Number: NCT03427125
• Lead Sponsor: Ardelyx

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.

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 Timeline

• Study Start: 2018-01-08
• Study First Submitted: 2018-01-19
• Study First Submitted QC: 2018-02-02
• Study First Posted: 2018-02-09
• Primary Completion: 2019-11-15
• Study Completion: 2020-02-27
• Disposition First Submitted: 2020-08-11
• Results First Submitted: 2022-12-07
• Status Verified: 2023-06
• Results First Submitted QC: 2023-06-08
• Last Update Submitted: 2023-06-08
• Results First Posted: 2023-06-29
• Disposition First Posted: 2023-06-29
• Last Update Posted: 2023-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1559

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
Tenapanor 10 mg, 20 mg, 30 mg BID	Tenapanor	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
Sevelamer Carbonate	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)

Primary Outcome Measures

Name	Time	Method
Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the Responder Population	12 weeks (randomized withdrawal period)	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.

Secondary Outcome Measures

Name	Time	Method
Serum Phosphorus From Baseline	26 weeks (open label treatment period)	Serum Phosphorus from baseline (post washout) to end of 26 week period
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

Trial Locations

Locations (2)

Site 529; 🇺🇸 Bronx, New York, United States

Wake Forest School of Medicine; 🇺🇸 Winston-Salem, North Carolina, United States