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

• Reduction in mean weekly interdialytic weight gain (IDWG) [ Time Frame: Run-in period (Weeks -2 and -1) versus Week 4 (end of treatment) ] [ Designated as safety issue: No ]
  

• Stool sodium content [ Time Frame: Days 1 through 7 ] [ Designated as safety issue: No ]
  
• Reduction in mean weekly IDWG [ Time Frame: Run-in period (Weeks -2 and -1) versus weeks 1, 2, and 3 and follow-up, weeks 5 and 6 ] [ Designated as safety issue: No ]
  
• Plasma concentrations of study drug [ Time Frame: Study Days 1, 3, 5, 7 and 29 ] [ Designated as safety issue: Yes ]
  
• Evaluate the safety and tolerability of 4 weeks of treatment [ Time Frame: Weeks 1, 2, 3, and 4 ] [ Designated as safety issue: Yes ]
  AEs, SAEs, and safety laboratory evaluations.
  
  

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.