A Study to Test Whether ZS (Sodium Zirconium Cyclosilicate) Can Reduce the Incidence of Increased Blood Potassium Levels Among Dialized Patients.

NCT03303521 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: D9480C000062017-003029-14
• Study Type: interventional
• Target: 196
• Locations: 4 countries
• Sites: 53

Brief Summary

The purpose of this study is to evaluate the efficacy of ZS in the treatment of hyperkalemia in patients on hemodialysis.

Conditions

Hyperkalemia

Outcome Measures

Primary Outcomes (2)

• Percentage of Responders

  A subject was considered to be a responder if, during the evaluation period, they maintained a pre-dialysis serum potassium (S-K) between 4.0 and 5.0 mmol/L on at least 3 out of 4 dialysis treatments following the long inter-dialytic interval and did not receive rescue therapy. The S-K levels used for this analysis were based on the measurements obtained by the central laboratory.

  Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.

• Percentage of Responders When Accounting for Missing Central Laboratory Serum Potassium Data

  The sensitivity analysis assessed the impact of subjects classified as non-responders due to missing serum potassium (S-K) data. Missing central lab (c-lab) pre-dialysis values were imputed using corresponding pre-dialysis i-STAT (a portable blood analyser) measurements. In addition, a "last observation carried forward" (LOCF) approach was utilized to further impute missing values of pre-dialysis S-K during the evaluation period. This technique will replace missing c-lab S-K values with the last available non-missing pre-dialysis LIDI observation recorded for that patient (and this could be a c-lab value or an imputed c-lab value). The Primary endpoint analysis was repeated on the imputed data.

  Evaluation period runs over the last 4 weeks of the treatment period up to 8 weeks, starting after visit 11 and ending on visit 15, thus it comprises post-long inter-dialytic interval visits 12, 13, 14 and 15.

Secondary Outcomes (1)

• Percentage of Patients Needing Rescue Therapy

  An 8 week overall treatment period (a 4 week adjustment phase plus a 4 week evaluation phase) and a 2 week follow up period.

Study Arms (2)

Sodium Zirconium Cyclosilicate (ZS)

EXPERIMENTAL

Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.

Drug: Sodium Zirconium Cyclosilicate (ZS)

Placebo

PLACEBO COMPARATOR

Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.

Drug: Placebo

Interventions

Placebo DRUG

Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) . Single dose contains from 1 to 3 sachets of Placebo depending on dose level assigned to a patient per non-dialysis days.

Placebo

Sodium Zirconium Cyclosilicate (ZS) DRUG

Suspension administered orally for a treatment period of eight weeks (4 weeks of dose adjustment, 4 weeks in stable dose) . Single dose contains from 1 to 3 sachets of ZS 5g depending on dose level assigned to a patient per non-dialysis days.

Sodium Zirconium Cyclosilicate (ZS)

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
• Female or male aged ≥ 18 years at screening Visit 1. For patients aged \<20 years and enrolled in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative.
• Receiving hemodialysis (or hemodiafiltration) 3 times a week for treatment of endstage renal disease (ESRD) for at least 3 months before randomization.
• Patients must have hemodialysis access consisting of an arteriovenous fistula, AV graft, or tunneled (permanent) catheter which is expected to remain in place for the entire duration of the study.
• Pre-dialysis serum K \>5.4 mmol/L after long inter-dialytic interval and \>5.0 mmol/L after one short inter-dialytic interval during screening (as assessed by central lab).
• Prescribed dialysate K concentration ≤ 3 mmol/L during screening
• Sustained Qb ≥200 ml/min and spKt/V ≥1.2 (or URR ≥ 63) on stable hemodialysis/hemodiafltration prescription during screening with prescription (time, dialyzer, blood flow \[Qb\], dialysate flow rate \[Qd\] and bicarbonate concentration) expected to remain unchanged during study
• Heparin dose (if used) must be stable during screening and expected to be stable during the study
• Subjects must be receiving dietary counseling appropriate for ESRD patients treated with hemodialysis/hemodiafiltration as per local guidelines, which includes dietary potassium restriction.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca, including ZS Pharma staff and/or staff at the study site)
• Hemoglobin \<9 g/dL on screening (as assessed on Visit 1)
• Lack of compliance with hemodialysis prescription (both number and duration of treatments) during the two-week period preceding screening (100% compliance required)
• Patients treated with sodium polystyrene sulfonate (SPS, Kayexalate, Resonium), calcium polystyrene sulfonate (CPS, Resonium calcium) or patiromer (Veltassa) within 7 days before screening or anticipated in requiring any of these agents during the study
• Myocardial infarction, acute coronary syndrome, stroke, seizure or a thrombotic/thromboembolic event (e.g., deep vein thrombosis or pulmonary embolism, but excluding vascular access thrombosis) within 12 weeks prior to randomization
• Laboratory diagnosis of hypokalemia (K \< 3.5 mmol/L), hypocalcemia (Ca \< 8.2 mg/dL; for Japan hypocalcemia is defined as albumin-corrected Ca \< 8.0 mg/dL), hypomagnesemia (Mg \< 1.7 mg/dL) or severe acidosis (serum bicarbonate 16 mEq/L or less) in the 4 weeks preceding randomization
• Pseudohyperkalemia secondary to hemolyzed blood specimen (this situation is not considered screening failure, sampling or full screening can be postponed to a later time as applicable).
• Severe leukocytosis (\>20× 10\^9/L) or thrombocytosis (≥450 × 10\^9/L) during screening
• Polycythemia (Hb \>14 g/dL) during screening
• Diagnosis of rhabdomyolysis during the 4 weeks preceding randomization
• Patients treated with lactulose, xifaxan (rifaximin) or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug
• Patients unable to take oral ZS drug mix
• Scheduled date for living donor kidney transplant
• Patients with a life expectancy of less than 6 months
• Female patients who are pregnant or breastfeeding

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (53)

Research Site

Los Angeles, California, 90022, United States

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Los Angeles, California, 90025, United States

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Ontario, California, 91762, United States

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San Dimas, California, 91773, United States

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Whittier, California, 90606, United States

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Kansas City, Missouri, 64108, United States

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St Louis, Missouri, 63110, United States

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Paterson, New Jersey, 07504, United States

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Fresh Meadows, New York, 11365, United States

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Great Neck, New York, 11021, United States

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Ridgewood, New York, 11385, United States

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The Bronx, New York, 10461, United States

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East Providence, Rhode Island, 02914, United States

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El Paso, Texas, 79924, United States

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Houston, Texas, 77004, United States

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Hamamatsu, 432-8036, Japan

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Kumamoto, 860-4112, Japan

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Miyagi-gun, 981-0112, Japan

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Nagano, 388-8004, Japan

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Niigata, 950-2087, Japan

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Ora-gun, 370-0615, Japan

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Osaka, 543-0052, Japan

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Sakaishi, 599-8272, Japan

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Sashima-gun, 306-0433, Japan

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Sendai, 980-0801, Japan

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Shinjuku-ku, 169-0075, Japan

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Toride-shi, 302-0022, Japan

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Tsukuba, 305-0861, Japan

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Wakayama, 640-8335, Japan

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Yachiyo-shi, 276-0031, Japan

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Yokosuka-shi, 238-0004, Japan

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Kemerovo, 650066, Russia

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Kolomna, Russia

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Moscow, 141007, Russia

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Novosibirsk, 630087, Russia

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Omsk, 644111, Russia

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Penza, 440034, Russia

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Podolsk, Russia

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Rostov-on-Don, 344029, Russia

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Saint Petersburg, 191104, Russia

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Saint Petersburg, 196247, Russia

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Saint Petersburg, 198205, Russia

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Yaroslavl, 150062, Russia

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Yekaterinburg, 620102, Russia

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Cardiff, CF14 4XW, United Kingdom

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Hull, HU3 2JZ, United Kingdom

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Leicester, LE5 4PW, United Kingdom

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London, EC1A 7BE, United Kingdom

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London, SE5 9RS, United Kingdom

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London, SM5 1AA, United Kingdom

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London, SW17 0QT, United Kingdom

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Swansea, SA6 6NL, United Kingdom

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York, YO31 8HE, United Kingdom

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Related Publications (2)

• Fishbane S, Ford M, Fukagawa M, McCafferty K, Rastogi A, Spinowitz B, Staroselskiy K, Vishnevskiy K, Lisovskaja V, Al-Shurbaji A, Guzman N, Bhandari S. Potassium responses to sodium zirconium cyclosilicate in hyperkalemic hemodialysis patients: post-hoc analysis of DIALIZE. BMC Nephrol. 2022 Feb 8;23(1):59. doi: 10.1186/s12882-021-02569-7.

  PMID: 35135481 DERIVED

• Natale P, Palmer SC, Ruospo M, Saglimbene VM, Strippoli GF. Potassium binders for chronic hyperkalaemia in people with chronic kidney disease. Cochrane Database Syst Rev. 2020 Jun 26;6(6):CD013165. doi: 10.1002/14651858.CD013165.pub2.

  PMID: 32588430 DERIVED

Related Links

• CSP redacted
• D9480C00006 SAP redacted

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: AstraZeneca Clinical
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Steven Fishbane, MD

  NSUH,Dept of Medicine,300 Community Drive,Manhasset,NY11030

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: September 26, 2017
• First Posted: October 6, 2017
• Study Start: December 14, 2017
• Primary Completion: November 7, 2018
• Study Completion: November 7, 2018
• Last Updated: February 20, 2020
• Results First Posted: February 20, 2020

Record last verified: 2020-02

Locations

US (15); RU (13); GB (9); JP (16)