Pharmacodynamic Study of AZD1722 in End-stage Renal Disease Patients on Hemodialysis

A Phase 2a, Randomized, Double-Blind, Placebo-Controlled, Parallel Design Study to Evaluate the Pharmacodynamics, Safety, and Tolerability of AZD1722 in End-Stage Renal Disease Patients on Hemodialysis

The purpose of this study is to determine if the study drug is safe, tolerable and active in reducing fluid overload/weight gain between dialysis sessions for patients with End Stage Renal Disease on Hemodialysis.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease; ESRD; Chronic Kidney Disease Stage 5
• Intervention / Treatment: Drug: AZD1722 (in-patient); Drug: Placebo (in-patient); Drug: AZD1722 (out-patient); Drug: Placebo

Detailed Description

This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacodynamics of the study drug in male and female patients with end-stage renal disease on hemodialysis. The study consists of a 2 week treatment-free run-in period where entry criteria are verified, a 4-week treatment period, of which the first week of treatment will be performed as an in-patient study in a clinical pharmacology unit (CPU) and the remaining three weeks of treatment will performed as an out-patient study, and a 2-week treatment-free follow-up period.

Safety assessments will be performed at regular intervals and will include clinical and vital signs, clinical laboratory evaluations, ECGs, and AE monitoring. Pharmacodynamic assessments will include, but are not limited to, interdialytic weight gain (IDWG), blood pressure, and stool sodium excretion. Pharmacokinetic assessments will include blood sampling for measurement of study drug plasma concentrations.

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Southwest Clinical Research Institute
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Nephrology
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Davita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females aged 18 to 80 years, inclusive;
• Body mass index between 18 and 45 kg/m2, inclusive;
• Ambulatory (≥ 6 months) maintenance hemodialysis;
• Stable dialysis treatment regimen 3x/week for ≥ 2 months prior to screening visit.

Exclusion Criteria:

• Currently taking diuretic medication;
• Has a urine production of ≥ 200 ml/day (based on a 24-hour measurement starting on Day -1 and completed prior to randomization);
• Predialysis systolic BP >200 mmHg or diastolic BP >110 mmHg on two successive occasions during the 2-week run-in period;
• Predialysis SBP < 110 mmHg on two successive occasions during the 2-week run-in period

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD1722- in patient; Tenapanor administered in a clinical pharmacology unit	Drug: AZD1722 (in-patient); doses between 5 and 60 mg BID may be administered based on tolerability in a CPU setting; Other Names: RDX5791; Tenapanor
Placebo Comparator: Placebo- in patient; Placebo (size and color matched to experimental drug) administered in a clinical pharmacology unit	Drug: Placebo (in-patient); Placebo, size and color matched to experimental drug administered in a CPU
Experimental: AZD1722 out-patient; Tenapanor	Drug: AZD1722 (out-patient); doses between 5 and 45 mg BID; Other Names: Tenapanor
Experimental: Placebo out-patient; Placebo	Drug: Placebo; Placebo, size and color matched to experimental drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Weekly Interdialytic Weight Gain (IDWG)	Patients are weighed pre dialysis prior to their first dialysis of the week. This measure looks at the change in pre-dialysis weight over time	Run-in period (Weeks -2 and -1) versus Week 4 (end of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool Sodium Content	The amount of sodium in a days worth of stool output	Days 1 through 7

Collaborators and Investigators

• Sponsor: Ardelyx
• Collaborators: AstraZeneca
• Investigators: Study Director: David P Rosenbaum, PhD, Ardelyx, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): October 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: January 4, 2013
• First Submitted That Met QC Criteria: January 8, 2013
• First Posted (Estimate): January 10, 2013

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Hemodialysis
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: D5611C00001