Clinical trial NCT02875834: A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia
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-HARMONIZE Global
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperkalemia
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2016-08-23
Enrollment: 267
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* Provision of informed consent prior to any study specific procedures
* Female and male patients aged ≥18 and ≤ 90 years
* Two consecutive i-STAT potassium values, measured 60-minutes (± 10 minutes) apart, both ≥ 5.1 mmol/l and measured within 1 day of the first ZS dose on 48-hour open-label initial phase Day 1
* Ability to have repeated blood draws or effective venous catheterization
* Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy.

Exclusion Criteria:

* Involvement in the planning and/or conduct of the study
* Participation in another clinical study with an investigational product during the last 3 months
* Pseudohyperkalemia signs and symptoms
* Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
* Patients treated with resins,calcium acetate,calcium carbonate, or lanthanum carbonate,within 7 days prior to the first dose of study drug
* Patients with a life expectancy of less than 3 months
* Patients who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol
* Female patients who are pregnant, lactating, or planning to become pregnant
* Patients with diabetic ketoacidosis
* Presence of any condition which, in the opinion of the investigator, places the patient at undue risk or potentially jeopardizes the quality of the data to be generated
* Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
* Patients with cardiac arrhythmias that require immediate treatment
* Patients on dialysis
* Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS

Primary outcomes:
measure: Least Square Mean S-K Level on Days 8-29
timeFrame: Through 28-day randomized treatment study phase day 8-29.
Secondary outcomes:
measure: Proportion of Patients Achieving Normokalemia
timeFrame: Through 48-hour initial phase.
measure: Exponential Rate of Change in S-K Levels
timeFrame: Through 48-hour initial phase.
measure: Absolute Change From Baseline in S-K Levels
timeFrame: Through 48-hour initial phase.
measure: Percentage Change From Baseline in S-K Levels
timeFrame: Through 48-hour initial phase.
measure: Proportion of Patients Remaining Normokalemic
timeFrame: Through 28-day randomized treatment study phase day 8-29.
measure: Proportion of Normokalemic Patients at Day 1 Through Day 29/Exit
timeFrame: Through 28-day randomized treatment phase.
measure: Days Patients Remain Normokalemic
timeFrame: Through 28-day randomized treatment phase.
measure: Mean Change in S-K Levels
timeFrame: Through 28-day randomized treatment phase.
measure: Mean Percentage Change in S-K Levels
timeFrame: Through 28-day randomized treatment phase.
measure: Number of Hyperkalemic Patients
timeFrame: Through 28-day randomized treatment phase.
measure: Mean Changes in S-Aldosterone and P Renin Levels
timeFrame: Through 28-day randomized treatment phase.
measure: Patient Reported Health State (EQ-5D) Questionnaire
timeFrame: Through study completion, an average of 37 days.
Other outcomes:
Locations:
city: Chiba-shi
country: Japan
facility: Research Site
city: Hanyu-shi
country: Japan
facility: Research Site
city: Hitachinaka-shi
country: Japan
facility: Research Site
city: Ina-shi
country: Japan
facility: Research Site
city: Kanazawa-shi
country: Japan
facility: Research Site
city: Koga-shi
country: Japan
facility: Research Site
city: Matsudo-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Nagoya-shi
country: Japan
facility: Research Site
city: Shimajiri-gun
country: Japan
facility: Research Site
city: Shizuoka-shi
country: Japan
facility: Research Site
city: Toride-shi
country: Japan
facility: Research Site
city: Toyohashi-shi
country: Japan
facility: Research Site
city: Yao-shi
country: Japan
facility: Research Site
city: Anyang-si
country: Korea, Republic of
facility: Research Site
city: Bucheon-si
country: Korea, Republic of
facility: Research Site
city: Bucheon-si
country: Korea, Republic of
facility: Research Site
city: Busan
country: Korea, Republic of
facility: Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Goyang-si
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Hwaseong-si
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Incheon
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Suwon-si
country: Korea, Republic of
facility: Research Site
city: Uijeongbu-si
country: Korea, Republic of
facility: Research Site
city: Wonju-si
country: Korea, Republic of
facility: Research Site
city: Ekaterinburg
country: Russian Federation
facility: Research Site
city: Krasnoyarsk
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Saint Petersburg
country: Russian Federation
facility: Research Site
city: Saint-Petersburg
country: Russian Federation
facility: Research Site
city: Yaroslavl
country: Russian Federation
facility: Research Site
city: Hualien City
country: Taiwan
facility: Research Site
city: New Taipei
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taichung
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
Study officials:
References: