Dose Finding Study to Treat High Phosphate Levels in the Blood.

A Phase 2b, Randomized, Double Blind, Placebo-controlled, Parallel Group, Multicentre Dose Finding Study to Evaluate the Efficacy, Safety and Tolerability of AZD1722 to Treat Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)

Randomized. double blind, placebo controlled, parallel arms dose finding study with a 4 weeks treatment period

Study Overview

• Status: Completed
• Conditions: Hyperphosphatemia
• Intervention / Treatment: Drug: AZD1722; Drug: Placebo

Detailed Description

The study consists of a screening period of approximately 1 week, a wash out period of up to 3 weeks, where existing phosphate lowering medication is withheld, a 4-week treatment period and a follow-up period of up to 2 weeks, during which patients are put back on their pre washout phosphate lowering medication.

The wash out period will be either 1 week, 2 weeks or 3 weeks depending on the increase in s-phosphate levels.

There are 7 parallel treatment arms in the study with bid and od treatment regimens.

Laboratory efficacy endpoints and safety assessments will be evaluated at various times throughout the study.

The target population of the study is: male or female patients, above18 years of age with End Stage Renal Disease (ESRD) on chronic maintenance hemodialysis (HD) 3 times a week for a minimum of 3 months.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Bialystok, Poland
    • Research Site
  • Czestochowa, Poland
    • Research Site
  • Dzialdowo, Poland
    • Research Site
  • Legnica, Poland
    • Research Site
  • Lublin, Poland
    • Research Site
  • Radom, Poland
    • Research Site
  • Szczecin, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
  • Wroclaw, Poland
    • Research Site
  • Zamosc, Poland
    • Research Site
  • Zary, Poland
    • Research Site
  • Zgierz, Poland
    • Research Site
• Slovakia
  • Banska Bystrica, Slovakia
    • Research Site
  • Bratislava, Slovakia
    • Research Site
  • Hlohovec, Slovakia
    • Research Site
  • Kosice, Slovakia
    • Research Site
  • Piestany, Slovakia
    • Research Site
  • Puchov, Slovakia
    • Research Site
  • Senica, Slovakia
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom
    • Research Site
  • Doncaster, United Kingdom
    • Research Site
  • Exeter, United Kingdom
    • Research Site
  • Hull, United Kingdom
    • Research Site
  • Leicester, United Kingdom
    • Research Site
  • London, United Kingdom
    • Research Site
• United States
  • California
    • Downey, California, United States
      • Research Site
    • Los Angeles, California, United States
      • Research Site
    • Sacramento, California, United States
      • Research Site
    • Whittier, California, United States
      • Research Site
  • Colorado
    • Denver, Colorado, United States
      • Research Site
  • Florida
    • Pembroke Pines, Florida, United States
      • Research Site
    • Tampa, Florida, United States
      • Research Site
    • Winter Park, Florida, United States
      • Research Site
  • Massachusetts
    • Springfield, Massachusetts, United States
      • Research Site
  • Michigan
    • Detroit, Michigan, United States
      • Research Site
  • New Jersey
    • Voorhees, New Jersey, United States
      • Research Site
  • New York
    • Flushing, New York, United States
      • Research Site
    • Maspeth, New York, United States
      • Research Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States
      • Research Site
  • Texas
    • San Antonio, Texas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Females and males aged ≥18 years
2. Chronic maintenance hemodialysis 3 x/week for a at least 3 months
3. Prescribed and taking at least 3 doses of phosphate binder per day
4. Serum phosphate levels should be between 3.5 and 8.0 mg/dL ; 1.13 mmol/L and 2.58 mmol/L (inclusive) at screening
5. Total serum calcium levels 2.0 - 2.6 mmol/L inclusive at screening
6. For randomization in the study, after up to 3 weeks wash out of phosphate binders, patients must have serum phosphate levels of at least 6. 0 mg/dL (1.94 mmol/L) but below 10 mg/dL (3.23 mmol/L) and have had an increase of at least 1.5 mg/dL (0.48 mmol/L) vs pre wash out

Exclusion Criteria:

1. Severe hyperphosphatemia defined as >10 mg/dL on Phosphate-binders at all time points during clinical routine monitoring for the 3 preceding months before screening visit.
2. Serum parathyroid hormone >1200 pg/mL
3. Significant metabolic acidosis

4. Clinical signs of hypovolemia at randomization

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 mg bid; 1 mg AZD1722 bid	Drug: AZD1722; AZD1722, oral tablet
Experimental: 3 mg bid; 3 mg AZD1722 bid	Drug: AZD1722; AZD1722, oral tablet
Experimental: 10 mg bid; 10 mg AZD1722 bid	Drug: AZD1722; AZD1722, oral tablet
Experimental: 30 mg bid; 30 mg AZD1722 bid	Drug: AZD1722; AZD1722, oral tablet
Experimental: 3 mg od; 3 mg AZD1722 od	Drug: AZD1722; AZD1722, oral tablet
Experimental: 30 mg od; 30 mg AZD1722 od	Drug: AZD1722; AZD1722, oral tablet
Placebo Comparator: Placebo; Placebo (double dummy technique)	Drug: Placebo; Placebo bid, double dummy technique

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Phosphate Levels	Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment	End of wash out (pre randomization value) to end of treatment (Day 29)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Calcium x Phosphorus Product	Change from baseline (end of wash out) in calcium x phosphorus product	End of wash out (pre randomization value) to end of treatment (Day 29)

Collaborators and Investigators

• Sponsor: Ardelyx
• Investigators: Principal Investigator: Geoffrey A Block, MD, Denver Nephrology PC, Denver, CO 80230

Publications and helpful links

General Publications

• Block GA, Rosenbaum DP, Yan A, Greasley PJ, Chertow GM, Wolf M. The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia. Nephrol Dial Transplant. 2019 Feb 1;34(2):339-346. doi: 10.1093/ndt/gfy061.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: March 6, 2014
• First Submitted That Met QC Criteria: March 6, 2014
• First Posted (Estimate): March 7, 2014

Study Record Updates

• Last Update Posted (Actual): September 14, 2020
• Last Update Submitted That Met QC Criteria: August 25, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: S-phosphate, hyperphosphatemia, hemodialysis, ESRD
• Additional Relevant MeSH Terms: Metabolic Diseases; Phosphorus Metabolism Disorders; Hyperphosphatemia
• Other Study ID Numbers: D5613C00001