ZS Ph2/3 Dose-response Study in Japan
A Phase 2/3 Multicenter, Dose-response Study to Assess Efficacy and Safety of ZS (Sodium Zirconium Cyclosilicate), in Japanese Patients With Hyperkalemia
1 other identifier
interventional
103
1 country
25
Brief Summary
To assess efficacy of 5 g three times daily (TID) and 10 g TID ZS versus placebo in Japanese patients with hyperkalemia (serum potassium \[S-K\] ≥ 5.1 mmol/L and ≤ 6.5 mmol/L).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jun 2017
Shorter than P25 for phase_2
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 5, 2017
CompletedFirst Posted
Study publicly available on registry
April 25, 2017
CompletedStudy Start
First participant enrolled
June 14, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 23, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
February 23, 2018
CompletedResults Posted
Study results publicly available
May 20, 2019
CompletedMay 20, 2019
February 1, 2019
8 months
April 5, 2017
February 20, 2019
February 20, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Exponential Rate of Change in Serum Potassium (S-K) Values During the Initial 48 Hours of Study Drug Treatment
Blood samples for determination of potassium were collected pre-dose, and at 1, 2, and 4 hours post Dose 1 on Day 1. An additional sample was collected at 90 minutes post Dose 2 on Day 1 if i-STAT potassium values at the 4-hour post Dose 1 time point was ≥ 6.1 or \<4.0 mmol/L. On Day 2 samples were analysed pre-dose, and 1 and 4 hours post Dose 1. S-K levels were analysed at the Central Laboratory. Natural logarithm of S-K from 0 to 48 hours post dose are modelled by the random coefficients model including fixed effects of intercept, time, time x treatment and patient-level random effects for time and intercept. Exponential rate of change refers to the slope estimate from the random coefficients model.
From 0 to 48 hours.
Secondary Outcomes (8)
Percentage of Patients Who Achieved Normokalaemia at 48 Hours
At 48 hours.
Exponential Rate of Change in S-K Values During the Initial 24 Hours of Study Drug Treatment
From 0 to 24 hours.
Percentage of Patients Who Achieved Normokalaemia at 24 Hours
At 24 hours.
Percentage of Patients Who Achieved Normokalaemia at Each Scheduled Potassium Assessment Time Point
From baseline to end of study (9 days).
Mean Change From Baseline in S-K Values at All Measured Time Intervals
From baseline to end of study (9 days).
- +3 more secondary outcomes
Study Arms (3)
Sodium Zirconium Cyclosilicate (ZS) 5g
EXPERIMENTALSuspension administered 5g orally three times daily for 48 hours.
Sodium Zirconium Cyclosilicate (ZS) 10g
EXPERIMENTALSuspension administered 10g orally three times daily for 48 hours.
Placebo
PLACEBO COMPARATORPlacebo suspension administered orally placebo three times daily for 48 hours.
Interventions
Suspension administered 5g orally three times daily for 48 hours.
Suspension administered 10g orally three times daily for 48 hours.
Eligibility Criteria
You may qualify if:
- Provision of informed consent prior to any study specific procedures.
- Patients aged ≥18. For patients aged \<20 years, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
- Two consecutive i-STAT potassium values, measured 60 (± 10) minutes apart, both values should be ≥ 5.1 mmol/L and ≤ 6.5 mmol/L and measured within 1 day before the first dose of study drug on Study 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 (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) 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.
You may not qualify if:
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- Cause or symptoms of pseudohyperkalemia, such as
- hemolyzed blood specimen due to excessive fist clenching to make veins prominent
- hemolyzed blood specimen due to difficult or traumatic venepuncture
- history of severe leukocytosis or thrombocytosis
- Patients treated with lactulose, rifaximin, or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of study drug on Study Day 1
- Patients treated with resins (such as sevelamer hydrochloride, sodium polystyrene sulfonate \[SPS; e.g. Kayexalate®\] or calcium polystyrene sulfonate \[CPS\]), 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 patients' tasks associated with the protocol
- Female patients who are pregnant, lactating, or planning to become pregnant
- Patients who have an active or history of 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
- Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry
- Patients with cardiac arrhythmias that require immediate treatment
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (25)
Research Site
Chiba, 260-8712, Japan
Research Site
Chiba, 263-0043, Japan
Research Site
Hanyu-shi, 348-8505, Japan
Research Site
Higashiibaraki-gun, 311-3193, Japan
Research Site
Hitachi-Naka, 312-0057, Japan
Research Site
Ina-shi, 396-8555, Japan
Research Site
Kagoshima, 892-8580, Japan
Research Site
Kahoku-gun, 920-0293, Japan
Research Site
Kamakura-shi, 247-8533, Japan
Research Site
Kanazawa, 920-8650, Japan
Research Site
Kasugai-shi, 486-8510, Japan
Research Site
Kawachinagano-shi, 586-8521, Japan
Research Site
Kawasaki-shi, 216-8511, Japan
Research Site
Kitakyushu-shi, 802-0001, Japan
Research Site
Koga-shi, 306-0041, Japan
Research Site
Kusatsu-shi, 525-8585, Japan
Research Site
Matsudo-shi, 271-0077, Japan
Research Site
Matsuyama, 791-8026, Japan
Research Site
Nagoya, 457-8511, Japan
Research Site
Naka, 311-0113, Japan
Research Site
Omura-shi, 856-8562, Japan
Research Site
Shimajiri-gun, 901-0493, Japan
Research Site
Shizuoka, 421-0117, Japan
Research Site
Yakushi, 581-0011, Japan
Research Site
Yotsukaido-shi, 284-0027, Japan
Related Publications (1)
Kashihara N, Nishio T, Osonoi T, Saka Y, Imasawa T, Ohtake T, Mizuno H, Shibagaki Y, Kim H, Yajima T, Sarai N. Correction of serum potassium with sodium zirconium cyclosilicate in Japanese patients with hyperkalemia: a randomized, dose-response, phase 2/3 study. Clin Exp Nephrol. 2020 Dec;24(12):1144-1153. doi: 10.1007/s10157-020-01937-1. Epub 2020 Aug 10.
PMID: 32779057DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Global Clinical Lead
- Organization
- AstraZeneca
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 5, 2017
First Posted
April 25, 2017
Study Start
June 14, 2017
Primary Completion
February 23, 2018
Study Completion
February 23, 2018
Last Updated
May 20, 2019
Results First Posted
May 20, 2019
Record last verified: 2019-02