Overview

This trial is active, not recruiting.

Condition hyperkalemia
Treatments zirconium silicate (acute phase), zirconium silicate (maintenance phase), silicilate microcrystaline cellulose (maintenance phase)
Phase phase 3
Sponsor ZS Pharma, Inc.
Start date March 2014
End date August 2014
Trial size 275 participants
Trial identifier NCT02088073, ZS-004

Summary

It is hypothesized that ZS is more effective than placebo control (alternative hypothesis) in maintaining mean double-blind randomized maintenance phase (DBRMP) Day 8-29 serum potassium levels (3.5 - 5.0 mmol/l, inclusive) among hyperkalemic subjects in whom normokalemia was established during the open-label acute phase versus no difference between each ZS dose (highest to lowest) versus placebo control (null hypothesis).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose supportive care
Arm
(Experimental)
Open label oral administration of zirconium silicate 10g three times a day for 48 hours.
zirconium silicate (acute phase) ZS
Oral 10g three times a day with meals for 48 hours.
(Experimental)
Randomized oral doses (5g, 10g, and 15g) of microporous, fractionated, protonated zirconium silicate administered once daily with breakfast for 28 days.
zirconium silicate (maintenance phase) ZS
Oral doses (either 5g, 10g, or 15g) once daily with breakfast for 28 days.
(Placebo Comparator)
Randomized to mimic doses of experimental drug administered once daily with breakfast for 28 days.
silicilate microcrystaline cellulose (maintenance phase) Placebo
Oral dose once daily with breakfast for 28 days.

Primary Outcomes

Measure
Maintenance of serum potassium level with once daily ZS for 28 days after establishment of normokalemia with ZS three times a day for first 48 hours.
time frame: First 48 hours acute phase, then 28 days maintenance phase

Secondary Outcomes

Measure
Proportion of subjects who convert from hyperkalemia to normokalemia after 10g ZS three times a day.
time frame: First 48 hours

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Provision of written informed consent. - Over 18 years of age. - Two consecutive i-STAT potassium values, measured 60-minutes apart, both ≥5.1 mmol/l and measured within 1 day of the first ZS dose on AP Study Day 1. - Ability to have repeated blood draws or effective venous catheterization. - Women of childbearing potential must be using two forms of medically acceptable contraception (at least one barrier method) and have a negative pregnancy test at AP Study Day 1. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of childbearing potential. Exclusion Criteria: - Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen, history of severe leukocytosis or thrombocytosis. - Subjects treated with lactulose, Xifaxan or other non-absorbed antibiotics for hyperammonemia within 7 days prior to the first dose of study drug. - Subjects treated with resins (such as sevelamer acetate or sodium polystyrene sulfonate [SPS; e.g. Kayexalate®]), calcium acetate, calcium carbonate, or lanthanum carbonate, within 7 days prior to the first dose of study drug. - Subjects with a life expectancy of less than 3 months. - Subjects who are severely physically or mentally incapacitated and who in the opinion of investigator are unable to perform the subjects' tasks associated with the protocol. - Women who are pregnant, lactating, or planning to become pregnant. - Subjects with diabetic ketoacidosis. - Presence of any condition which, in the opinion of the investigator, places the subject 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. - Randomization into the previous ZS-002 or ZS-003 studies. - Treatment with a drug or device within the last 30 days that has not received regulatory approval at the time of study entry. - Subjects with cardiac arrhythmias that require immediate treatment. - Subjects on dialysis.

Additional Information

Official title Multicenter, Multi-phase, Multi-dose, Prospective, Double-blind, Placebo-controlled, Maintenance Study of Safety and Efficacy of ZS (Microporous, Fractionated, Protonated Zirconium Silicate) in Hyperkalemia.
Description Approximately 275 subjects with hyperkalemia (two consecutive i-STAT potassium levels ≥ 5.1 mmol/l, taken 60 minutes apart at baseline) will be enrolled in the Open-label Acute Phase to provide 232 subjects in the Double Blind Randomized Maintenance Phase. Initially all subjects will receive open-label ZS at a dose of 10g three times a day (tid) for 48 hours (AP). Subjects who achieve normokalemia (i-STAT potassium values between 3.5 to 5.0 mmol/l, inclusive) on the morning of Study Day 3 (after 6 doses of 10g ZS) will then, in a double-blind fashion, be randomized 4:4:4:7 to receive one of three doses of ZS (5g, 10g or 15g) or placebo control, qd for the following 28 days (DBRMP). Safety and tolerability will be assessed on an ongoing basis by an Independent Data Monitoring Committee (iDMC). Each active dose group in the DBRMP will consist of 49 subjects and the placebo control group will consist of 85 subjects for a total of 232 subjects to detect a 0.6 effect size difference between each ZS dose (from highest to lowest) and placebo control; the 4:4:4:7 allocation optimizes the multiple comparisons to the placebo control for the DBRMP.
Trial information was received from ClinicalTrials.gov and was last updated in August 2014.
Information provided to ClinicalTrials.gov by ZS Pharma, Inc..