HARMONIZE Asia: A Study to Investigate the Safety and Efficacy of ZS in Patients With Hyperkalemia.

• Sponsor: AstraZeneca (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT03528681
• Collaborator: (none)
• Enrollment: 280
• Locations: 41
• Arms: 3
• Anticipated Duration (Months): 16.3
• Patients Per Site: 6.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Hyperkalemia	Drug: Sodium Zirconium Cyclosilicate 5g; Drug: Sodium Zirconium Cyclosilicate 10g; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 6, 2021
• Anticipated Primary Completion Date: Sep 13, 2022
• Anticipated Study Completion Date: Sep 13, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sodium Zirconium Cyclosilicate 10g Suspension administered 10g orally once daily for 28 days after the open label initial phase.	Drug: Sodium Zirconium Cyclosilicate 10g; Suspension administered Sodium Zirconium Cyclosilicate 10g orally once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.
Experimental: Sodium Zirconium Cyclosilicate 5g Suspension administered 5g orally once daily for 28 days after the open label initial phase.	Drug: Sodium Zirconium Cyclosilicate 5g; Suspension administered Sodium Zirconium Cyclosilicate 5g orally once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.
Placebo Comparator: Matching Placebo Suspension administered orally placebo once daily for 28 days after the open label initial phase.	Drug: Placebo; Suspension administered orally placebo once daily for 28 days after the open label initial phase with suspension administered Sodium Zirconium Cyclosilicate 10g orally three times per day for at most 2 days.

Outcome Measures

Primary Outcome Measures

1. Least Squares Means of S-K values during the 28-day randomized treatment study phase Study Days 8-29. [Through 28 day randomized treatment study phase day 8-29]

   Comparison between placebo and each ZS treatment group (high to low) with regard to the mean S-K level during the 28-day randomized treatment study phase Days 8-29

Secondary Outcome Measures

1. Exponential rate of change in S-K levels [Through open label initial phase]

   Exponential rate of change in S-K levels (blood) during the open label initial phase

2. Mean change from baseline in S-K levels [Through open label initial phase]

   Mean Change (absolute and percent change) from baseline in S-K levels (blood) at all measured time intervals post dose in the open label initial phase

3. proportion of patients achieve normokalemia [Through open label initial phase]

   Proportion of patients who achieve normokalemia during the open label initial phase at 24 hours and at the end of the open label phase

4. Time to normalization in S-K levels [Through open label initial phase]

   Time to normalization in S-K levels (normalization defined as S-K levels between 3.5-5.0 mmol/L, inclusive) in the open label initial phase

5. Proportion of patients remaining normokalemic [Through 28-day randomized treatment study 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

6. Mean number of Days patients remain normokalemic [Through 28-day randomized treatment study phase]

   The mean number of days patients remain normokalemic during the 28-day randomized treatment study phase

7. Mean change and mean percent change in S-K levels [Through 28-day randomized treatment study phase]

   The mean change and mean percent change in S-K levels evaluated relative to both baselines

8. Time to hyperkalemia [Through 28-day randomized treatment study phase]

   The time to hyperkalemia (defined as S-K ≥5.1mmol/L)

9. Mean changes in S-Aldo and P-Renin levels [Through 28-day randomized treatment study phase]

   The mean changes in S-Aldo and P-Renin levels

Other Outcome Measures

1. Vital signs [Throughout the study, from the time of signature of the main study informed consent form up to study completion.]

   Vital signs include pulse rate and blood pressure

2. ECG measurements [Throughout the study, from the time of signature of the main study informed consent form up to study completion.]

   ECG measurements include heart rate, P and QRS durations, PR and QTc(f) intervals. Collected from standard lead of the computerized quantitative 12- lead ECG.

3. AEs, including SAEs [Throughout the study, from the time of signature of the main study informed consent form up to study completion.]

   The evaluation of AE will include, but not be limited to, a classification by SOC/PT, an assessment of severity and causality with regards to the IP, as well as action taken as the response to the AE, e.g. IP discontinuation

4. Safety laboratory evaluations, including determination of hypokalaemia [Throughout the study, from the time of signature of the main study informed consent form up to study completion.]

   Include, but are not limited to, serum potassium, calcium, magnesium, sodium, phosphate, bicarbonate, as well as blood urea nitrogen.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Beijing		China	100029
2	Research Site	Beijing		China	100144
3	Research Site	Beijing		China	102206
4	Research Site	Bengbu		China	233060
5	Research Site	Changsha		China	430033
6	Research Site	Chengdu		China	610041
7	Research Site	Chengdu		China	610072
8	Research Site	Dongguan		China	523009
9	Research Site	Fuzhou		China	350005
10	Research Site	Guangzhou		China	510080
11	Research Site	Guangzhou		China	510120
12	Research Site	Guiyang		China	550004
13	Research Site	Hangzhou		China	310003
14	Research Site	Hefei		China	230022
15	Research Site	Jingzhou		China	434020
16	Research Site	Kunming		China	650021
17	Research Site	Lanzhou		China	730030
18	Research Site	Nanchang		China	330006
19	Research Site	Shanghai		China	200025
20	Research Site	Shanghai		China	200090
21	Research Site	Shanghai		China	200127
22	Research Site	Suzhou		China	215006
23	Research Site	Taiyuan		China	030001
24	Research Site	Taiyuan		China	030012
25	Research Site	Tianjin		China	300121
26	Research Site	Tianjin		China	300211
27	Research Site	Wuhan		China	430030
28	Research Site	Xian		China	710061
29	Research Site	Xining		China	810001
30	Research Site	Yangzhou		China	225001
31	Research Site	Yichang		China	443003
32	Research Site	Yinchuan		China	750004
33	Research Site	Zhanjiang		China	524001
34	Research Site	Zhuzhou		China	412007
35	Research Site	Ahmedabad		India	380006
36	Research Site	Ahmedabad		India	380015
37	Research Site	Bengaluru		India	560004
38	Research Site	Nagpur		India	440012
39	Research Site	New Delhi		India	110002
40	Research Site	New Delhi		India	110017
41	Research Site	Vijayawada		India	522002

Sponsors and Collaborators

• AstraZeneca

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03528681
• Other Study ID Numbers: D9480C00001
• First Posted: May 18, 2018
• Last Update Posted: Jul 12, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hyperkalemia

Study Results

No Results Posted as of Jul 12, 2022