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

Ardelyx

Status and phase: Completed; Phase 3

Conditions: Hyperphosphatemia

Treatments: Drug: Sevelamer Carbonate; Drug: Tenapanor; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03427125

TEN-02-301

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1,559 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,559 participants in 3 patient groups, including a placebo group

Tenapanor 10 mg, 20 mg, 30 mg BID

Experimental group

Description:

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

Treatment:

Drug: Tenapanor

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Drug: Placebo

Sevelamer Carbonate

Active Comparator group

Description:

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)

Treatment:

Drug: Sevelamer Carbonate