Clinical trial NCT03528681: 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 (Sodium Zirconium Cyclosilicate), in Patients With Hyperkalemia-HARMONIZE Asia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperkalemia
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2018-05-18
Enrollment: 270
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 24 or 48 hours of initial ZS therapy (10g TID).

Detailed description: This study will be conducted in approximately 35 centers in China. Before patients are randomized to the double-blind phase, they will receive open-label ZS for 24 or 48 hours during the initial phase. It is expected that approximately 490 patients will need to be enrolled, to have approximately 280 patients entered into the open-label initial phase resulting in 250 patients being randomized in the 28-day treatment study phase. Enrolment will be stopped when 250 patients have been initiated with the 28-day randomized treatment study phase.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent (pre-screening consent) prior to any study specific procedures
2. Female and male patients aged ≥18 and ≤ 90 years
3. Provision of informed consent prior to any study specific procedures
4. 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 open-label initial phase Day 1
5. Ability to have repeated blood draws or effective venous catheterization
6. Female patients must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 3 months after the last dose of ZS/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study
2. Participation in another clinical study with an investigational product during the last 3 months
3. 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
4. Pseudohyperkalemia signs and symptoms, such as hemolyzed blood specimen due to excessive fist clenching to make veins prominent, difficult or traumatic venepuncture, or history of severe leukocytosis or thrombocytosis
5. Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
6. Patients treated with resins,calcium acetate,calcium carbonate, or lanthanum carbonate,within 7 days prior to the first dose of study drug
7. Patients with a life expectancy of less than 3 months
8. 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
9. Female patients who are pregnant, lactating, or planning to become pregnant
10. Patients with diabetic ketoacidosis
11. Known hypersensitivity or previous anaphylaxis to ZS or to components thereof
12. Patients with cardiac arrhythmias that require immediate treatment
13. History of QT prolongation associated with other medications that required discontinuation of that medication.
14. Congenital long QT syndrome
15. Symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted
16. QTc(f) \> 550 msec
17. Patients on dialysis
18. Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of ZS
19. Patients who need hospitalization after taking blood samples on day 1 of the open-label initial phase

Primary outcomes:
measure: Least Square Mean S-K Level on Days 8-29
timeFrame: Days 8 to 29 (Randomized treatment study phase) used for model-based least squares mean computation
Secondary outcomes:
measure: Percentage of Patients Who Achieve Normokalemia
timeFrame: Through open label initial phase
measure: Exponential Rate of Change in S-K Levels
timeFrame: Through 24 hours post-dose in the initial phase
measure: Absolute Change From Baseline in S-K Levels
timeFrame: Through open label initial phase
measure: Percentage Change From Baseline in S-K Levels
timeFrame: Through open label initial phase
measure: Proportion of Patients Who Remain Normokalemic During RTP
timeFrame: Through 28-day randomized treatment study phase day 8-29
measure: Proportion of Normokalemic Patients at the End of RTP
timeFrame: The end of 28-day randomized treatment study phase
measure: Days Patients Remain Normokalemic
timeFrame: Through days 8-29 of the randomized treatment phase.
measure: Mean Change in S-K Levels
timeFrame: Through 28-day randomized treatment phase.
measure: Mean Percent Change in S-K Levels
timeFrame: Through 28-day randomized treatment phase.
measure: Least Square Mean Changes in S-Aldo and P-Renin Levels
timeFrame: Through 28 day randomized treatment study phase day 15-29
measure: Hyperkalaemia at Day 29
timeFrame: Day 29
measure: Percentage of Patients Without Hyperkalemia
timeFrame: Day 29 of randomized treatment phase
Other outcomes:
Locations:
city: Baotou
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Bengbu
country: China
facility: Research Site
city: Changchun
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Dalian
country: China
facility: Research Site
city: Dongguan
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Fuzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guiyang
country: China
facility: Research Site
city: Haikou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Jilin
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jingzhou
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Nanchang
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuxi
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Xian
country: China
facility: Research Site
city: Xining
country: China
facility: Research Site
city: Xining
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Yichang
country: China
facility: Research Site
city: Yinchuan
country: China
facility: Research Site
city: Zhanjiang
country: China
facility: Research Site
city: Zhuzhou
country: China
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Bengaluru
country: India
facility: Research Site
city: Chandigarh
country: India
facility: Research Site
city: Chennai
country: India
facility: Research Site
city: Hyderabad
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Nagpur
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Vijayawada
country: India
facility: Research Site
Study officials:
References: