An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
Condition: Hyperphosphatemia
MeSH terms: Kidney Failure, Chronic; Hyperphosphatemia
Intervention: Tenapanor; Placebo
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 219.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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.
    

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