Open-label Safety of Sodium Zirconium Cyclosilicate for up to 12 Months in Japanese Subjects With Hyperkalemia

NCT ID: NCT03172702

Last Updated: 2020-05-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-04
• Study Completion Date: 2019-07-06

Brief Summary

The Open-Label Maintenance Study contains an Correction Phase, in which subjects will be dosed with ZS 10 g three times daily (tid) for 24 to 72 hours, followed by a 12-month long-term Maintenance Phase.

Detailed Description

The study will start with the screening period, and all baseline parameters should be measured/collected up to 1 day prior to administration of first dose of study drug on Correction Phase Day 1. Subjects with 2 consecutive i-STAT potassium values ≥ 5.1 mmol/L will enter the Correction Phase and receive ZS 10 g TID for up to 72 hours, depending on potassium values. Once normokalemia (i-STAT potassium between 3.5 and 5.0 mmol/L, inclusive) is restored (whether after 24, 48 or 72 hours), subjects will be entered into the Maintenance Phase to be dosed with ZS at a starting dose of 5 g QD. Potassium (i-STAT and Central Laboratory) will be measured Days 1, 2, 5, 12, 19 and 26 throughout the first month of study and every 4 weeks thereafter until Day 362 (Visit 23) then patients will be required to complete the EOS visit which is 7±1 days after the last administration of study medication. For patients who do not enter the Maintenance Phase the last visit will be 7±1 day after the last treatment dose in the Correction Phase. The total expected study duration for an individual patient is approximately 53-54 weeks.

Conditions

Hyperkalemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Sodium Zirconium Cyclosilicate

Correction Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) from 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) (or 2.5 g QD) based on i-STAT potassium measurements up to 12 months.

Group Type: EXPERIMENTAL

Zirconium Cyclosilicate

Intervention Type: DRUG

Correction Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) from 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) (or 2.5 g QD) based on i-STAT potassium measurements up to 12 months.

Interventions

Zirconium Cyclosilicate

Correction Phase Dosing: Sodium Zirconium Cyclosilicate 10 g three times daily (TID) from 24 to 72 Extended Dosing: Sodium Zirconium Cyclosilicate 5 g once daily (QD). Sodium Zirconium Cyclosilicate dose increased or decreased in increments/decrements of 5 g QD up to a maximum of 15 g QD or a minimum of 5 g every other day (QOD) (or 2.5 g QD) based on i-STAT potassium measurements up to 12 months.

Intervention Type: DRUG

Other Intervention Names

ZS

Eligibility Criteria

Inclusion Criteria

• 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-minutes (± 15 minutes) apart, both ≥ 5.1 mmol/L and measured within 1 day before the first dose of ZS on Correction Phase Study Day 1.
• Patients who are on peritoneal dialysis (PD) can be enrolled if their SK level is ≥5.5 and ≤ 6.5 mmol/L in two consecutive i-STAT potassium evaluation at least 24 hours apart before Day 1 (in each evaluation, two i-STAT potassium measurements at least 1 hour apart are required). i-STAT potassium measurement should be performed in the morning before breakfast and in the evening before dinner in PD patients on continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD), respectively.
• Women of childbearing potential must be using 2 forms of medically acceptable contraception (at least 1 barrier method) and have a negative pregnancy test within 1 day prior to the first dose of ZS on Correction Phase Study Day 1. Women who are surgically sterile or those who are postmenopausal for at least 1 year are not considered to be of childbearing potential.

Exclusion Criteria

• Patients treated with lactulose, rifaxan (rifaximin), or other non-absorbed antibiotics for hyperammonemia within 7 days prior to first dose of ZS.
• 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. Washout of SPS and CPS for 7 days (or longer) prior to the first dose of ZS is allowed, if termination of CPS or SPS is judged to be clinically acceptable by the investigator. Documented informed consent has to be obtained prior to the washout.
• Patients with a life expectancy of less than 12 months
• Female patients who are pregnant, lactating, or planning to become pregnant
• Patients who have an active or history of diabetic ketoacidosis
• 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
• Hemodialysis patients (including those who are on both PD and hemodialysis [HD])
• Patients who have been on PD less than 6 months or more than 6 months with a history of hypokalemia within 6 months before Correction Phase Day 1
• Documented Glomerular Filtration Rate (GFR) < 15 mL/min within 90 days prior to study entry (Non peritoneal dialysis (PD) patients only)
• If patients joined ZS study in the past, the patients cannot join this study within the last 30 days of the last study drug administration day.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Akashi-shi, , Japan

Research Site

Amagasaki-shi, , Japan

Research Site

Chiba, , Japan

Research Site

Chiba, , Japan

Research Site

Chiyoda-ku, , Japan

Research Site

Chūōku, , Japan

Research Site

Funabashi-shi, , Japan

Research Site

Hanyu-shi, , Japan

Research Site

Higashiibaraki-gun, , Japan

Research Site

Hitachi-Naka, , Japan

Research Site

Ina-shi, , Japan

Research Site

Kagoshima, , Japan

Research Site

Kahoku-gun, , Japan

Research Site

Kamakura-shi, , Japan

Research Site

Kasuga-shi, , Japan

Research Site

Kasugai-shi, , Japan

Research Site

Kasugai-shi, , Japan

Research Site

Kawachinagano-shi, , Japan

Research Site

Kawasaki-shi, , Japan

Research Site

Kitakyushu-shi, , Japan

Research Site

Kochi, , Japan

Research Site

Koga-shi, , Japan

Research Site

Koga-shi, , Japan

Research Site

Kumamoto, , Japan

Research Site

Matsudo-shi, , Japan

Research Site

Matsuyama, , Japan

Research Site

Minokamo-shi, , Japan

Research Site

Mito, , Japan

Research Site

Nagoya, , Japan

Research Site

Naka, , Japan

Research Site

Omura-shi, , Japan

Research Site

Onomichi-shi, , Japan

Research Site

Osaka, , Japan

Research Site

Osaka, , Japan

Research Site

Osaka, , Japan

Research Site

Shimajiri-gun, , Japan

Research Site

Shizuoka, , Japan

Research Site

Toride-shi, , Japan

Research Site

Toshima-ku, , Japan

Research Site

Toyohashi, , Japan

Research Site

Yakushi, , Japan

Research Site

Yotsukaido-shi, , Japan

Countries

Japan

References

Kashihara N, Yamasaki Y, Osonoi T, Harada H, Shibagaki Y, Zhao J, Kim H, Yajima T, Sarai N. A phase 3 multicenter open-label maintenance study to investigate the long-term safety of sodium zirconium cyclosilicate in Japanese subjects with hyperkalemia. Clin Exp Nephrol. 2021 Feb;25(2):140-149. doi: 10.1007/s10157-020-01972-y. Epub 2020 Oct 24.

Reference Type: DERIVED

PMID: 33098526 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Related Links

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Other Identifiers

D9482C00001

Identifier Type: -

Identifier Source: org_study_id