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

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.

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