Hyperkalemia
Conditions
Brief summary
It is hypothesized that SPS is more effective than placebo control (alternative hypothesis) in lowering i-STAT potassium levels in subjects with i-STAT potassium levels between 5.0 - 6.5 mmol/l versus no difference between SPS and placebo control (null hypothesis).
Detailed description
Subjects with mild to moderate hyperkalemia (i-STAT potassium levels between 5.0-6.5 mmol/l, inclusive) will be randomized 1:1 in a double-blind fashion to receive placebo or SPS (15g), administered tid with meals for 48 hours. Subjects will come back to the clinic on Study Day 9 for an End of Study (EOS) visit. Adverse experiences will be recorded. Blood potassium levels will be evaluated by both i-STAT and the Local Laboratory prior to the first dose on Study Days 1 and 2, 1, 2, and 4 hours after the first dose on Study Day 1, 1 and 4 hours after the first dose on Study Day 2 and prior to breakfast on Study Day 3, after 48 hours of treatment. Subjects who have i-STAT potassium levels \> 6.5 mmol/l on Study Day 1 at the 4 hour post Dose 1 time point will be withdrawn from the study and will receive standard of care. If the i-STAT potassium value is between 6.1 and 6.5 mmol/l at the 4-hour post Dose 1 draw, subjects will be kept in the clinic for another 90 minutes post Dose 2 and another blood draw will be taken and an ECG will be performed. If the i-STAT potassium level is ≥ 6.2 mmol/l at this time point, the subject will be discontinued from the study and standard of care will be instituted. If the i-STAT potassium level is \< 6.2 mmol/l, and the ECG does not show any of the ECG withdrawal criteria (see below), the subject will continue in the study.
Interventions
Oral suspension in water of 15g sodium polystyrene sulfonate administered three times (tid) daily for 48 hours without co-administration of Sorbitol.
DRUGSilicified microcrystalline cellulose
Oral suspension in water of placebo administered three times (tid) daily for 48 hours.
Sponsors
ZS Pharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent. * Over 18 years of age. * Mean i-STAT potassium values between 5.0 - 6.5 mmol/l inclusive, at screening (Study Day 0). * Previous participation in Clinical ZS-002 or ZS-003 protocol(s). However, subjects cannot be enrolled in this study until at least 30 days have elapsed from their last dose in study ZS-003. * 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 screening. Women who are surgically sterile or those who are post-menopausal for at least 2 years are not considered to be of child-bearing potential.
Exclusion criteria
* Pseudohyperkalemia signs and symptoms, such as excessive fist clenching hemolyzed blood specimen, severe leukocytosis or thrombocytosis. * Subjects treated with lactulose, Xifaxan or other non-absorbed antibiotics for hyperammonemia within the last 7 days. * Subjects treated with resins (such as Sevelamer acetate), calcium acetate, calcium carbonate, or lanthanum carbonate, within the last 7 days. * Subjects treated with Sodium Polystyrene Sulfonate (SPS; e.g. Kayexalate®) or ZS (microporous, fractionated, protonated zirconium silicate) within the last 30 days. * Subjects with a life expectancy of less than 3 months. * Subjects who are HIV positive. * 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. * Previous treatment with SPS. * 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 insulin where a stable dose has not yet been established.\* * Subjects on dialysis. \* Subjects on stable insulin or insulin analogues can be enrolled. Subjects who have been on the same insulin dose and regimen for \> 14 days are considered stable. Whenever possible, all blood draws collected prior to meals should be collected prior to insulin/insulin analogue treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Potassium Levels From Baseline After Administration of Sodium Polystyrene Sulfonate (SPS) Three Times a Day Without Co-administration of Sorbitol; Determine Incidence of Adverse Events. | First 48 hours | To perform a controlled evaluation of the safety and efficacy of 15g of SPS administered 3 times daily for 48 hours (6 doses) in patients with hyperkalemia (serum potassium levels between 5.0 - 6.5 mmol/l) at baseline. |
Secondary
| Measure | Time frame |
|---|---|
| Change in Serum Sodium, Magnesium, Calcium Levels From Baseline After Administration of SPS. | First 48 hours |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sodium Polystyrene Sulfonate Oral suspension in water of 15g sodium polystyrene sulfonate administered three times (tid) daily for 48 hours without co-administration of Sorbitol.
Sodium polystyrene sulfonate (ACTIVE)
Total Study Enrollment: Assessed for eligibility (n= 36 )
Excluded (n= 4)
* Not meeting inclusion criteria (n= 4 )
* Declined to participate (n= 0)
* Other reasons (n= 0 )
Total Randomized (n= 32 )
Allocated to intervention (n= 15 ): ACTIVE
* Received allocated intervention (n= 15)
* Did not receive allocated intervention (give reasons) (n= 0 )
Lost to follow-up (give reasons) (n= 0 )
Discontinued intervention before study terminated (n= 1): non-serious adverse event
Analysed (n= 0)
◻ Excluded from analysis (give reasons) (n= 15): study terminated early due to safety reasons | 15 |
| Silicified Microcrystalline Cellulose Oral suspension of placebo blended with pigment to have the same appearance, taste, odor and mode of administration as SPS.
Silicified microcrystalline cellulose (PLACEBO)
Total Study Enrollment: Assessed for eligibility (n= 36 )
Excluded (n= 4)
* Not meeting inclusion criteria (n= 4 )
* Declined to participate (n= 0)
* Other reasons (n= 0 )
Total Randomized (n= 32 )
Allocated to intervention (n= 17): PLACEBO
* Received allocated intervention (n= 17 )
* Did not receive allocated intervention (give reasons) (n= 0)
Lost to follow-up (give reasons) (n= 0 )
Discontinued intervention (give reasons) (n= 0)
Analysed (n= 0)
◻ Excluded from analysis (give reasons) (n= 17): study terminated early due to safety reasons | 17 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Sodium Polystyrene Sulfonate | Silicified Microcrystalline Cellulose | Total |
|---|---|---|---|
| Age, Continuous | 71.1 years | 70.5 years | 70.8 years |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 15 | 3 / 17 |
| serious Total, serious adverse events | 2 / 15 | 0 / 17 |
Outcome results
Primary
Change in Serum Potassium Levels From Baseline After Administration of Sodium Polystyrene Sulfonate (SPS) Three Times a Day Without Co-administration of Sorbitol; Determine Incidence of Adverse Events.
To perform a controlled evaluation of the safety and efficacy of 15g of SPS administered 3 times daily for 48 hours (6 doses) in patients with hyperkalemia (serum potassium levels between 5.0 - 6.5 mmol/l) at baseline.
Time frame: First 48 hours
Population: Study prematurely terminated for safety reasons; no statistical analyses were conducted.
Secondary
Change in Serum Sodium, Magnesium, Calcium Levels From Baseline After Administration of SPS.
Time frame: First 48 hours
Population: Study was prematurely terminated for safety reasons; no statistical analyses were conducted.