A Safety and Pharmacodynamic Study of Healthy Chinese Subjects Administered Sodium Zirconium Cyclosilicate (ZS)

A Single-center Safety and Pharmacodynamic Study of Healthy Chinese Subjects Administered Sodium Zirconium Cyclosilicate (ZS)

This is a single center, inpatient, open label pharmacodynamic study to determine the effect of 5 g and 10 g doses of Sodium Zirconium Cyclosilicate (ZS) administered once daily (qd) for 4 days on potassium and sodium excretion in healthy Chinese subjects on a standardized, low sodium and high potassium diet.

Study Overview

• Status: Completed
• Conditions: Hyperkalemia
• Intervention / Treatment: Drug: Sodium Zirconium Cyclosilicate (ZS)

Detailed Description

This study will be conducted at 1 study centre in Hong Kong. Approximately 22 Subjects will be screened to achieve 20 subjects completing the study. Subjects will be randomized to receive ZS 5 g or 10 g (1:1) once daily (qd) in conjunction with breakfast and will be continued with a standard diet during the ZS treatment period.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female and/or male healthy Chinese subjects aged between 18 and 55 inclusive who reside in Hong Kong
3. Ability to have repeated blood draws or effective venous catheterization
4. Willing to consume food and beverages using a standardized daily diet containing 40 (± 10%) mEq/day sodium and 128 (± 10%) mEq/day potassium provided by the research site

Key Exclusion Criteria:

1. Participation in another clinical study with an investigational product during the last 3 months
2. Subjects who were receiving concomitant medications including vitamins, dietary supplements and herbal preparations within 2 weeks prior to Study Day 1 of the Diet Run-in Period.
3. Current and/or past history of alcohol abuse within the past year or a positive results (exceed normal range) of breath test for alcohol abuse
4. Current and/or past history of drugs abuse within the past year or a positive drug abuse screen, e. g. methylenedioxymethamphetamine, opiate, barbiturates, benzodiazepines, ketamine, cocaine, amphetamine, methamphetamine, marijuana, and methadone.
5. Plasma donation within 1 month of screening or any blood donation/blood loss >500 mL during the 3 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZS 5g, qd; Subjects randomized to this arm will receive ZS 5 g qd in conjunction with breakfast during the ZS treatment period and will be continued with a standard diet.	Drug: Sodium Zirconium Cyclosilicate (ZS); Sodium zirconium cyclosilicate (ZS) is a non-absorbed, inorganic crystalline compound that selectively captures potassium ions in exchange for sodium and hydrogen ions in the gastrointestinal tract after oral administration.
Experimental: ZS 10g, qd; Subjects randomized to this arm will receive ZS 10 g qd in conjunction with breakfast during the ZS treatment period and will be continued with a standard diet.	Drug: Sodium Zirconium Cyclosilicate (ZS); Sodium zirconium cyclosilicate (ZS) is a non-absorbed, inorganic crystalline compound that selectively captures potassium ions in exchange for sodium and hydrogen ions in the gastrointestinal tract after oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline to ZS treatment period in urine potassium excretion.	The 48- hour urine potassium excretion on Study Days 3 and 4 (baseline) will be compared with 48-hour urine potassium excretion on Study Days 7 and 8 (on study drug).	Study Day 3 and 4 vs Study Day 7 and 8.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline to ZS treatment period in urine sodium excretion.	The 48- hour urine sodium excretion on Study Days 3 and 4 (baseline) will be compared with 48- hour urine sodium excretion on Study Days 7 and 8 (on study drug).	Study Day 3 and 4 vs Study Day 7 and 8.
Mean change from baseline to ZS treatment period in serum potassium (S-K).	Mean change in S-K from the Baseline Period (Day 3 and 4) to the ZS Treatment Period (Day 7 and 8).	Study Day 3 and 4 vs Study Day 7 and 8.

Other Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events	From Day 1 through Follow-up visit
Changes in vital signs	Through study completion, up to 10 days
Changes in standard Electrocardiograph (ECG ) parameters	Through study completion, up to 10 days
Changes in standard physical examination parameters including height	Through study completion, up to 10 days
Changes in standard clinical chemistry lab parameters	Through study completion, up to 10 days
Changes in standard hematology lab parameters	Through study completion, up to 10 days
Changes in Serum calcium (S-Ca)	Through study completion, up to 10 days
Changes in Serum magnesium (S-Mg)	Through study completion, up to 10 days
Changes in Serum sodium (S-Na)	Through study completion, up to 10 days
Changes in Serum phosphate (S-PO4)	Through study completion, up to 10 days
Changes in Serum bicarbonate (S-HCO3)	Through study completion, up to 10 days
Changes in Blood urea nitrogen (BUN)	Through study completion, up to 10 days
Number of subjects with Serious adverse events	Through study completion and follow-up visit, up to 34 Days

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2017
• Primary Completion (Actual): November 23, 2017
• Study Completion (Actual): November 23, 2017

Study Registration Dates

• First Submitted: August 21, 2017
• First Submitted That Met QC Criteria: September 12, 2017
• First Posted (Actual): September 14, 2017

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 18, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Healthy Chinese Subjects, Pharmacodynamic Study
• Additional Relevant MeSH Terms: Metabolic Diseases; Water-Electrolyte Imbalance; Hyperkalemia
• Other Study ID Numbers: D9483C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No