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

NCT03172702 | Completed Phase 3 Results

• 1 other identifier: D9482C00001
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 42

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.

Conditions

Hyperkalemia

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Experienced Adverse Events (AEs) in the MP

  The number of patients who experienced any AE, including those which were serious (SAE), had an outcome of death, were severe, led to discontinuation of ZS or were causally related to ZS are presented for the MP. AEs of special interest are also presented, including oedema-related AEs, cardiac failure and hypertension.

  First MP dose up to 1 day (2 days for QOD regimen) after last MP dose.

Secondary Outcomes (16)

• Percentage of Patients Who Were Normokalemic in the MP

  MP Day 1 to End of Study visit (up to 12 months).

• Percentage of Patients With Average S-K Levels of ≤5.1 mmol/L and ≤5.5 mmol/L in the MP

  MP Day 2 to Day 362.

• Percentage of Patients Who Were Hypokalemic in the MP

  MP Day 1 to End of Study visit (up to 12 months).

• Percentage of Patients Who Were Hyperkalemic in the MP

  MP Day 1 to End of Study visit (up to 12 months).

• Mean Change From CP Baseline in the Mean S-K Level Over Specified Time Periods in the MP

  CP Day 1 to MP Day 362.

Study Arms (1)

Sodium Zirconium Cyclosilicate

EXPERIMENTAL

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.

Drug: Zirconium Cyclosilicate

Interventions

Zirconium Cyclosilicate 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.

Also known as: ZS

Sodium Zirconium Cyclosilicate

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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-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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (42)

Research Site

Akashi-shi, 674-0063, Japan

Location

Research Site

Amagasaki-shi, 660-8550, Japan

Location

Research Site

Chiba, 260-8712, Japan

Location

Research Site

Chiba, 263-0043, Japan

Location

Research Site

Chiyoda-ku, 101-0047, Japan

Location

Research Site

Chūōku, 104-0031, Japan

Location

Research Site

Funabashi-shi, 273-8588, Japan

Location

Research Site

Hanyu-shi, 348-8505, Japan

Location

Research Site

Higashiibaraki-gun, 311-3193, Japan

Location

Research Site

Hitachi-Naka, 312-0057, Japan

Location

Research Site

Ina-shi, 396-8555, Japan

Location

Research Site

Kagoshima, 892-8580, Japan

Location

Research Site

Kahoku-gun, 920-0293, Japan

Location

Research Site

Kamakura-shi, 247-8533, Japan

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Research Site

Kasuga-shi, 816-0864, Japan

Location

Research Site

Kasugai-shi, 486-8510, Japan

Location

Research Site

Kasugai-shi, 487-0016, Japan

Location

Research Site

Kawachinagano-shi, 586-8521, Japan

Location

Research Site

Kawasaki-shi, 216-8511, Japan

Location

Research Site

Kitakyushu-shi, 802-0001, Japan

Location

Research Site

Kochi, 780-0082, Japan

Location

Research Site

Koga-shi, 306-0014, Japan

Location

Research Site

Koga-shi, 306-0041, Japan

Location

Research Site

Kumamoto, 861-8520, Japan

Location

Research Site

Matsudo-shi, 271-0077, Japan

Location

Research Site

Matsuyama, 791-8026, Japan

Location

Research Site

Minokamo-shi, 505-8503, Japan

Location

Research Site

Mito, 311-4153, Japan

Location

Research Site

Nagoya, 457-8511, Japan

Location

Research Site

Naka, 311-0113, Japan

Location

Research Site

Omura-shi, 856-8562, Japan

Location

Research Site

Onomichi-shi, 732-8503, Japan

Location

Research Site

Osaka, 530-0001, Japan

Location

Research Site

Osaka, 558-8558, Japan

Location

Research Site

Osaka, 559-0012, Japan

Location

Research Site

Shimajiri-gun, 901-0493, Japan

Location

Research Site

Shizuoka, 421-0117, Japan

Location

Research Site

Toride-shi, 302-0022, Japan

Location

Research Site

Toshima-ku, 170-0003, Japan

Location

Research Site

Toyohashi, 441-8570, Japan

Location

Research Site

Yakushi, 581-0011, Japan

Location

Research Site

Yotsukaido-shi, 284-0027, Japan

Location

Related Publications (1)

• 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.

  PMID: 33098526 DERIVED

Related Links

• D9482C0000 redacted CSP
• D9482C00001 redacted SAP

MeSH Terms

Conditions

Hyperkalemia

Interventions

sodium zirconium cyclosilicate

Condition Hierarchy (Ancestors)

Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

+18772409479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2017
• First Posted: June 1, 2017
• Study Start: September 4, 2017
• Primary Completion: July 6, 2019
• Study Completion: July 6, 2019
• Last Updated: May 1, 2020
• Results First Posted: May 1, 2020

Record last verified: 2020-04

Locations

JP (42)