An 8-Week Study to Evaluate Tenapanor in the Treatment of Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)

Overview

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.

Full Title of Study: “An 8-week, Multicenter, Randomized, Double-Blind, Parallel Group Study With a 4-week, Placebo-Controlled, Randomized Withdrawal Period to Evaluate the Efficacy, Safety, and Tolerability of Tenapanor to Treat Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Triple (Participant, Care Provider, Investigator)
  • Study Primary Completion Date: December 2016

Detailed Description

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.

Interventions

  • Drug: Tenapanor
  • Drug: Placebo

Arms, Groups and Cohorts

  • Experimental: 3mg BID
    • Tenapanor, 3mg BID (6mg total)
  • Experimental: 10mg BID
    • Tenapanor, 10mg BID (20mg total)
  • Experimental: Dose Titration
    • Tenapanor, patients start at 30mg BID and can down titrate weekly to 20, 15, 10, and 3mg BID, sequentially based on a GI tolerability question
  • Placebo Comparator: Placebo
    • Placebo

Clinical Trial Outcome Measures

Primary Measures

  • Placebo Adjusted Change in Serum Phosphate During Randomized Withdrawal Period From Pooled Tenapanor Arms
    • Time Frame: 4 weeks
    • Serum phosphorus difference between placebo and tenapanor in the change from the end of the 8 week treatment period to the end of the randomized withdrawal period in Efficacy Analysis Set. The efficacy analysis was pre-defined to be a pooled analysis of all tenapanor treated patients with a minimum of a 1.2 mg/dL decrease in serum phosphorus during the 8-week treatment period

Secondary Measures

  • Change in Serum Phosphate During 8-Week Treatment Period
    • Time Frame: Baseline and 8 weeks
    • Serum phosphorus difference between baseline (end of washout period) to the end of the 8 week treatment period in ITT analysis set

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ardelyx
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • David P Rosenbaum, Ph.D., Study Chair, Ardelyx, Inc.

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