Clinical trial NCT03427125: A Phase 3 Study of Tenapanor to Treat Hyperphosphatemia in ESRD Patients on Dialysis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperphosphatemia
Lead sponsor: Ardelyx
Sponsor class: INDUSTRY
First posted: 2018-02-09
Enrollment: 1559
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the Responder Population
timeFrame: 12 weeks (randomized withdrawal period)
Secondary outcomes:
measure: Change in Serum Phosphorus Levels During Placebo Controlled Randomized Withdrawal Period in the ITT Population
timeFrame: 12 weeks (randomized withdrawal period)
measure: Serum Phosphorus From Baseline
timeFrame: 26 weeks (open label treatment period)
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Site 529
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest School of Medicine
state: North Carolina
Study officials:
affiliation: Ardelyx
name: David P Rosenbaum, PhD
role: STUDY_DIRECTOR
References:
citation: 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.