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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
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

Conditions
-----------------
End Stage Renal Disease, Chronic Kidney Disease Stage 5, ESRD

Intervention / Treatment
-----------------
* Drug: AZD1722 (in-patient)
* Drug: Placebo (in-patient)
* Drug: AZD1722 (out-patient)
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hemodialysis