Phase 3 N=258 Randomized Quadruple-blind Supportive Care

Safety & Efficacy of Zirconium Silicate Dosed for 28 Days in Hyperkalemia.

Hyperkalemia

Bottom Line

View on ClinicalTrials.gov: NCT02088073 ↗

Enrolled (actual)

258

Serious AEs

2.0%

Results posted

Dec 2018

Primary outcome: Primary: Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population). — 5.0603; 4.7544; 4.5081; 4.3742 mmol/L

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: Sodium zirconium cyclosilicate (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: ZS Pharma, Inc.
Primary completion: Aug 2014

Outcome Measures

Outcome	Result	p-value
PRIMARY Mean Serum Potassium Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT Population).	5.0603; 4.7544; 4.5081; 4.3742	—
SECONDARY The Number of Normokalemic Days Between Maintenance Phase Study Days 8 to 29, Inclusive (MP-ITT).	7.4; 13.4; 13.9; 16.8	—
SECONDARY Mean Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit .	5.55; 5.53; 5.58; 5.55; -0.86; -1.03	—
SECONDARY Mean Percent Change in S-K Levels From Acute Phase Baseline to Maintenance Phase Study Day 2 to Day 29/Exit, Inclusive .	-15.11; -18.53; -22.19; -20.04; -8.45; -12.84	—
SECONDARY Mean Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.	4.55; 4.51; 4.38; 4.45; 0.13; -0.01	—
SECONDARY Mean Percent Change in S-K Levels From Maintenance Phase Baseline to Maintenance Phase Day 2 to Day 29/Exit.	3.39; 0.06; -0.51; -0.20; 11.64; 6.93	—
SECONDARY Median Time to Hyperkalemia (S-K ≥ 5.1mmol/L)	7; 14; NA; NA	—
SECONDARY Mean S-K Intra-subject Standard Deviation Calculated Among Subjects With ≥ 2 Values on or After Maintenance Phase Study Day 8	0.06392; 0.06367; 0.07708; 0.06849	—
SECONDARY Proportion of Subjects Who Remained Normokalemic During Maintenance Phase	0.866; 0.933; 0.920; 0.926; 0.84; 0.933	—
SECONDARY Median Time to Relapse in S-K Values	19; 29; NA; NA	—
SECONDARY Exponential Rate of Change in S-K Values During the Acute Phase at 24 Hours and 48 Hours of Study Drug Treatment.	-0.00373; -0.00324	—
SECONDARY Mean Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.	5.55; -0.23; -0.41; -0.51; -0.68; -0.75	—
SECONDARY Mean Percent Change From Baseline in S-K Values (Blood) at All Measured Time Intervals Post Dose Acute Phase.	-3.91; -7.13; -9.00; -12.03; -13.41; -18.56	—
SECONDARY Proportion of Subjects Who Achieve Normokalemia During the Acute Phase at 24 and 48 Hours After Start of Dosing	0.661; 0.88	—
SECONDARY Median Time to Normalization (3.50-5.0 mmol/L) in S-K Levels in the 48 Hours of Initial Treatment	2.17	—

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).

Eligibility Criteria

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02088073). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.