an 8-week study to evaluate tenapanor in the treatment of hyperphosphatemia in end-stage renal disease patients on hemodialysis (esrd-hd)

Conditions: Hyperphosphatemia

Summary: this phase 3, 8-week, randomized, double-blind, parallel group, multi-center study with a 4-week, placebo-controlled, randomized withdrawal period will evaluate the efficacy, safety and tolerability of tenapanor to treat hyperphosphatemia in end-stage renal disease patients on hemodialysis (esrd-hd). subjects who qualify are randomized into the study will either receive 3 mg bid, 10 mg bid, or a titration regimen of tenapanor.

the study consists of a screening visit, a wash out period of up to 3 weeks, when existing phosphate lowering medication is withheld, an 8-week treatment period, in which all groups receive tenapanor, and a 4-week placebo-controlled, randomized withdrawal period, during which patients are re-randomized 1:1 to either remain on their current tenapanor treatment or placebo. depending on the increase in serum phosphate levels, subjects can be randomized 1,2, or 3 weeks after being taken off their phosphate lowering medication.

Eligibility criteria:
inclusion criteria: * 18 to 80 years old * 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/week for at least 3 months * kt/v ≥ 1.3 at most recent measurement prior to screening * prescribed and taking at least 3 doses of phosphate binder per day * serum phosphate levels should be between 4.0 and 7.0 mg/dl (inclusive) at screening * for randomization in the study, after 1 week wash-out of phosphate binders, subjects must have serum phosphate level of at least 9 mg/dl but below 10 mg/dl and have had an increase of at least 1.5 mg/dl versus pre-wash out value * for randomization in the study, after 2 or 3 weeks wash-out of phosphate binders, subjects must have serum phosphate level of at least 6 mg/dl but below 10 mg/dl and have had an increase of at least 1.5 mg/dl versus pre-wash out value exclusion criteria: * severe hyperphosphatemia defined as \>10 mg/dl on phosphate-binders at any time point during clinical routine monitoring for the 3 preceding months before screening * serum parathyroid hormone \>1200 pg/ml * persistent metabolic acidosis defined as serum carbon dioxide \<18 mmol/l from two consecutive measurements during screening and washout periods * clinical signs of hypovolemia at randomization * history of inflammatory bowel disease (ibd) or diarrhea predominant irritable bowel syndrome (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 * diarrhea or loose stools during the week before randomization defined as bsfs ≥ 6 and frequency ≥ 3 for 2 or more days * any evidence of or treatment of malignancy within one year, excluding non-melanomatous malignancies of the skin * positive serology with evidence of significant hepatic impairment or wbc elevation according to the investigator * life expectancy \< 6 months