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

• ClinicalTrials.gov Identifier: NCT03427125
• Recruitment Status: Completed
• First Posted: February 9, 2018
• Last Update Posted: August 25, 2020
• Sponsor: Ardelyx
• Information provided by (Responsible Party): Ardelyx

Tracking Information

• First Submitted Date: January 19, 2018
• First Posted Date: February 9, 2018
• Last Update Posted Date: August 25, 2020
• Actual Study Start Date: January 8, 2018
• Actual Primary Completion Date: November 15, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 2, 2018)

Change in serum phosphorus levels during placebo controlled randomized withdrawal period in the responder population [ Time Frame: 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 2, 2018)

• Change in serum phosphorus levels during placebo controlled randomized withdrawal period in the ITT Population [ Time Frame: 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 [ Time Frame: 26 weeks (open label treatment period) ]
  change from baseline (post washout) to end of 26 week period
• Effect of Tenapanor on serum FGF23 levels [ Time Frame: 52 weeks ]
  Change from baseline to end of different treatment periods

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis
• Official Title: A 26-Wk, Phase 3, Open Label Study With a 12-Wk, Placebo-Controlled, Randomized Withdrawal Period Followed by an Open Label Long Term Safety Extension to Evaluate the Safety and Efficacy of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis
• 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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Hyperphosphatemia

Intervention

• Drug: Tenapanor
  Active Drug
  Other Name: RDX5791, AZD1722
• Drug: Placebo
  Inactive Drug
• Drug: Sevelamer Carbonate
  Active control
  Other Name: Renvela

Study Arms

• 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
  Intervention: Drug: Tenapanor
• Placebo Comparator: Placebo
  Placebo
  Intervention: Drug: Placebo
• 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)
  Intervention: Drug: Sevelamer Carbonate

• Publications *: Block GA, Bleyer AJ, Silva AL, Weiner DE, Lynn RI, Yang Y, Rosenbaum DP, Chertow GM. Safety and Efficacy of Tenapanor for Long-term Serum Phosphate Control in Maintenance Dialysis: A 52-Week Randomized Phase 3 Trial (PHREEDOM). Kidney360. 2021 Aug 27;2(10):1600-1610. doi: 10.34067/KID.0002002021. eCollection 2021 Oct 28.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2019): 564
• Original Estimated Enrollment (submitted: February 2, 2018): 560
• Actual Study Completion Date: February 27, 2020
• Actual Primary Completion Date: November 15, 2019 (Final data collection date for primary outcome measure)

Eligibility 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
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03427125
• Other Study ID Numbers: TEN-02-301
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ardelyx
• Original Responsible Party: Same as current
• Current Study Sponsor: Ardelyx
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Ardelyx
• Verification Date: August 2020