Clinical Trial: A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 3 Multicenter, Prospective, Randomized, Double-blind, Placebo-controlled Study to Investigate the Safety and Efficacy of ZS, in Patients With Hyperkalemia-HARMONIZ

Brief Summary: To evaluate the efficacy of two different doses (5 and 10 g) of ZS orally administered once daily (qd) vs placebo in maintaining normokalemia in initially hyperkalemic patients having achieved normokalemia following two days of initial ZS therapy (10g TID).

Detailed Summary:
Sponsor: AstraZeneca

Current Primary Outcome: Least Square Mean S-K level on days 8-29 [ Time Frame: Through 28-day randomized treatment study phase day 8-29 ]

Comparison between placebo and the active ZS treatment groups (each dose group will be sequentially compared with placebo, starting with the highest and ending with the lowest dose) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Proportion of patients achieving normokalemia [ Time Frame: Through 48-hour initial phase ]
    Proportion of patients who achieve normokalemia during the initial phase at 24 and 48 hours
  • Exponential rate of change in S-K levels [ Time Frame: Through 48-hour initial phase ]
    Exponential rate of change in S-K levels (blood) during the 48-hour open-label initial phase
  • Change from baseline in S-K levels [ Time Frame: Through 48-hour initial phase ]
    Change (absolute and percent change) from baseline in S-K levels at all measured time intervals
  • Time to normalization in S-K levels [ Time Frame: Through 48-hour initial phase ]
    Time to normalization in S-K levels in 48-hour open-label initial phase
  • Proportion of patients remaining normokalemic [ Time Frame: Through 28-day randomized treatment phase ]
    The proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at the end of the 28-day randomized treatment study phase and during the 28-day randomized treatment study phase
  • Days patients remain normokalemic [ Time Frame: Through 28-day randomized treatment phase ]
    The number of days patients remain normokalemic during the 28-day randomized treatment study phase
  • Mean change and mean percent change in S-K levels [ Time Frame: Through 28-day randomized treatment phase ]
    The mean change and mean percent change in S-K levels evaluated relative to both baselines
  • Time to hyperkalemia [ Time Frame: Through 28-day randomized treatment phase ]
    The time to hyperkalemia (defined as S-K ≥ 5.1mmol/l)
  • Mean changes in S-Aldosterone and P Renin levels [ Time Frame: Through 28-day randomized treatment phase ]
    The mean changes in S-Aldosterone and P-Renin levels
  • Patient reported health state (EQ-5D questionnaire) [ Time Frame: Through study completion, an average of 37 days ]
    Evaluate health state of patients using EQ-5D


Original Secondary Outcome:

  • Proportion of patients achieving normokalemia [ Time Frame: Through 48-hour initial phase ]
    Proportion of patients who achieve normokalemia during the initial phase at 24 and 48 hours
  • Exponential rate of change in S-K levels [ Time Frame: Through 48-hour initial phase ]
    Exponential rate of change in S-K levels (blood) during the 48-hour open-label initial phase
  • Change from baseline in S-K levels [ Time Frame: Through 48-hour initial phase ]
    Change (absolute and percent change) from baseline in S-K levels at all measured time intervals
  • Time to normalization in S-K levels [ Time Frame: Through 48-hour initial phase ]
    Time to normalization in S-K levels in 48-hour open-label initial phase
  • Proportion of patients remaining normokalemic [ Time Frame: Through 28-day randomized treatment phase ]
    The proportion of patients who remain normokalemic (as defined by S-K between 3.5-5.0 mmol/l, inclusive) at the end of the 28-day randomized treatment study phase and the selected timepoints during 28-day randomized treatment study phase
  • Days patients remain normokalemic [ Time Frame: Through 28-day randomized treatment phase ]
    The number of days patients remain normokalemic during the 28-day randomized treatment study phase
  • Mean change and mean percent change in S-K levels [ Time Frame: Through 28-day randomized treatment phase ]
    The mean change and mean percent change in S-K levels at the selected timepoints evaluated relative to both baselines
  • Time to hyperkalemia [ Time Frame: Through 28-day randomized treatment phase ]
    The time to hyperkalemia (defined as S-K ≥ 5.1mmol/l)
  • Mean changes in S-Aldosterone and P Renin levels [ Time Frame: Through 28-day randomized treatment phase ]
    The mean changes in S-Aldosterone and P-Renin levels
  • Patient reported health state (EQ-5D questionnaire) [ Time Frame: Through study completion, an average of 37 days ]
    Evaluate health state of patients using EQ-5D


Information By: AstraZeneca

Dates:
Date Received: July 22, 2016
Date Started: March 3, 2017
Date Completion: February 12, 2018
Last Updated: April 24, 2017
Last Verified: April 2017