HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that supported the FDA approval of this drug, and whether there were differences among sex, race, and age groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your health provider about the risks and benefits of a drug. Refer to LOKELMA Prescribing Information for complete information.
LOKELMA (sodium zirconium cyclosilicate)
Lo-KELL-ma
AstraZeneca
Approval date: May 18,2018
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
LOKELMA is a drug for the treatment of hyperkalemia in adults.
Hyperkalemia is a condition in which the amount of potassium in the blood is too high.
How is this drug used?
LOKELMA is a powder that is mixed with water and taken three times a day for up to 48 hours. For patients needing continued treatment, the drug is taken once a day, with the dose adjusted as needed based on the amount of potassium in the blood.
What are the benefits of this drug?
LOKELMA reduced high levels of potassium in the blood and maintained the potassium at a normal level.
MORE INFO
What are the benefits of this drug (results of trials used to assess efficacy)?
The table below summarizes efficacy results for the Trial 1.
Table 2. Acute Phase Potassium Change from Baseline to 48 hours
| Mean Serum Potassium Change mEq/L (95% Confidence Intervals) Sample Size | Placebo | LOKELMA 1.25g TID | LOKELMA 2.5g TID | LOKELMA 5g TID | LOKELMA 10g TID |
|---|---|---|---|---|---|
| All Patients | -0.2 (-0.3, -0.2) n=158 | -0.3 (-0.4, -0.2) n=150 | -0.5 (-0.5, -0.4) n=137 | -0.5 (-0.6, -0.5) n=152 | -0.7 (-0.8, -0.7) n=140 |
| Baseline Serum Potassium >5.5 mEq/L | -0.4 (-0.6, -0.3) n=40 | -0.3 (-0.5, -0.2) n=40 | -0.6 (-0.7, -0.4) n=37 | -0.9 (-1.0, -0.7) n=29 | -1.1 (-1.3, -0.9) n=22 |
LOKELMA Prescribing Information
The figure below summarizes efficacy results for the Trial 2.
Figure 4. Mean Serum Potassium Levels Across Acute and Extended Phases (Trial 2)
LOKELMA Prescribing Information
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
- Sex: LOKELMA worked similarly in men and women.
- Race: LOKELMA worked similarly in White and Blacks or African American patients. The number of patients in other races was limited; therefore, differences in response to LOKELMA among all races could not be determined.
- Age: LOKELMA worked similarly in patients below and above 65 years of age.
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Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
The figures below summarize efficacy results by subgroup for each trial separately. The analysis is based on the Intent –to –treat (ITT) population.
Figure 5. Treatment Differences between LOKELMA 10 mg TID and Placebo Groups for Mean Change in Serum Potassium (mmol/L) from Extended Dosing Baseline to Day 12 by demographic Characteristics (Trial 1-ITT Population)
Adapted from FDA Statistical review
Figure 6. Treatment Difference between LOKELMA 10 mg TID and Placebo Groups for Mean Change in Serum Potassium (mmol/L) from Extended Dosing Baseline to Day 29 by demographic Characteristics (Trial 2-ITT Population)
Adapted from FDA Statistical review
What are the possible side effects?
The most common side effect of LOKELMA is body swelling because of its sodium content.
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What are the possible side effects (results of trials used to assess safety)?
In patients who were treated with once daily doses of LOKELMA for up to 28 days, edema was reported in 4.4% of patients receiving 5 g, 5.9% of patients receiving 10 g, and 16.1% of patients receiving 15 g LOKELMA compared to 2.4% of patients receiving placebo.
LOKELMA Prescribing Information
Were there any differences in side effects among sex, race and age?
- Sex: The risk of side effects was similar in men and women.
- Race: The risk of side effects was similar in White and Black or African American patients. The number of patients in other races was limited; therefore, differences in side effects among all races could not be determined.
- Age: The risk of side effects was similar in patients below and above 65 years of age.
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Were there any differences in side effects of the clinical trials among sex, race, and age groups?
The table below summarizes adverse reaction “edema” by subgroup. The analysis is based on pooled safety population from trials (maintenance phase).
Table 3. Subgroup Analysis of Edema Adverse Reaction during Maintenance Phase (Trials 1 and 2)
| LOKELMA | Placebo | |||
|---|---|---|---|---|
| n (%) | Total, n | n (%) | Total, n | |
| Overall | 17 (3.5) | 479 | 5 (1.7) | 301 |
| Sex | ||||
| Men | 12 (4.3) | 277 | 4 (2.2) | 178 |
| Women | 5 (2.5) | 202 | 1 (0.8) | 123 |
| Race | ||||
| White | 11 (2.7) | 415 | 4 (1.6) | 250 |
| Black or African American | 6 (10.7) | 56 | 1 (2.9) | 35 |
| All Other | 0 (0.0) | 8 | 0 (0.0) | 16 |
| Age Group | ||||
| <65> | 6 (2.9) | 207 | 2 (1.5) | 130 |
| >=65 years | 11 (4.0) | 272 | 3 (1.8) | 171 |
Clinical Trial Data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved LOKELMA based primarily on evidence from two clinical trials (Trial 1 #NCT01737697 and Trial 2 #NCT02088073) of patients with hyperkalemia. The trials were conducted in the USA, Australia and South Africa.
The figure below summarizes how many men and women were in the clinical trials.
Figure 1. Baseline Demographics by Sex
Clinical Trial Data
Figure 2 and Table 1 below summarize the percentage of patients by race in the clinical trials.
Figure 2. Baseline Demographics by Race
Clinical Trial Data
Table 1. Baseline Demographics by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 859 | 85 |
| Black or African American | 124 | 12 |
| Asian | 17 | 2 |
| Native Hawaiian or other Pacific Islander | 6 | 1 |
| American Indian or Alaska Native | 4 | less than 1 |
| Multiple | 1 | less than 1 |
Clinical Trial Data
Figure 3 summarizes the percentage of patients by age enrolled in the clinical trials.
Figure 3. Baseline Demographics by Age
Clinical Trial Data
MORE INFO
Who participated in the trials?
The table below summarizes demographics of patients in the clinical trials.
Table 4. Baseline Demographics of Patients in the Clinical Trials
| Demographic Subgroup | Trial 1 | Trial 2 | Total N=1011 n (%) |
|---|---|---|---|
| N=753 n (%) | N=258 n (%) | ||
| Sex | |||
| Men | 448 (59) | 149 (58) | 597 (59) |
| Women | 305 (41) | 109 (42) | 414 (41) |
| Race | |||
| White | 644 (86) | 215 (83) | 859 (85) |
| Black or African American | 87 (11) | 37 (14) | 124 (12) |
| Asian | 12 (2) | 5 (2) | 17 (2) |
| American Indian or Alaska Native | 4 (1) | 0 | 4 (<> |
| Native Hawaiian or other Pacific Islander | 5 (1) | 1 (<> | 6 (1) |
| Multiple | 1 (<> | 0 | 1(<> |
| Age Group | |||
| <65> | 310 (41) | 128 (50) | 438 (43) |
| ≥65 years | 443 (59) | 130 (50) | 573 (57) |
| Ethnicity | |||
| Hispanic or Latino | 231 (31) | 105 (41) | 336 (33) |
| Non-Hispanic or Latino | 522 (69) | 153 (59) | 675 (67) |
| Geographic Region | |||
| United States | 705 (94) | 206 (80) | 911 (90) |
| Outside United States | 48 (6) | 52 (20) | 100 (10) |
Clinical Trial Data
How were the trials designed?
The benefit and side effects of LOKELMA were evaluated in two clinical trials in patients with hyperkalemia. Each trial consisted of two parts.
In the first trial, patients with hyperkalemia received either LOKELMA at one of the four doses (1.25 g, 2.5 g, 5 g, or 10 g) or placebo three times a day for the first 48 hours. In the second part of the first trial, those patients who achieved normal potassium blood level received either LOKELMA at one of the four doses (1.25 g, 2.5 g, 5 g, or 10 g) or placebo once daily for 12 days. During the trial, neither the patients nor the health care providers knew which treatment was given.
In the second trial, all patients with hyperkalemia received 10 g of LOKELMA three times a day for the first 48 hours. In the second part of the trial, those patients who achieved normal potassium blood levels were randomized to one of three doses of LOKELMA administered once-daily for 28 days, or placebo. In this phase, neither patients not the health care providers knew which treatment was given.
The benefit of LOKELMA was assessed by measuring potassium level change over time and comparing it to placebo.
MORE INFO
How were the trials designed?
The safety and efficacy of LOKELMA were established in two randomized, multicenter trials.
Trial 1 was a two-part double-blind, randomized, placebo-controlled clinical trial In the first phase of the Trial 1 (the acute phase), patients were randomized to receive one of four doses of LOKELMA (1.25 g, 2.5 g, 5 g or 10 g) or placebo, administered three times daily for the initial 48 hours.
In the second phase of Trial 1 (maintenance phase), patients who achieved a potassium level between 3.5 and 5.0 mEq/L after receiving LOKELMA during the acute phase were re-randomized to receive once daily placebo or 1.25 g, 2.5 g, 5 g or 10 g of once daily LOKELMA for 12 days.
The primary endpoint in the acute phase was the difference in the exponential rate of change in serum potassium levels during the initial 48 hours of study drug treatment, comparing placebo-treated patients and LOKELMA-treated patients. The primary endpoint in the maintenance phase was the difference in the exponential rate of change in serum potassium levels over the 12-day treatment interval, comparing patients receiving LOKELMA and patients receiving placebo.
Trial 2 was a two-part trial with an open-label acute phase and a month long randomized, double-blind, placebo-controlled withdrawal phase.
In the open-label acute phase of the study, patients received 10 g of LOKELMA administered three times daily with meals for 48 hours.
In the second phase of Trial 2 days (the double-blind randomized withdrawal phase), patients who achieved a potassium level between 3.5 and 5.0 mEq were randomized in a double-blind fashion to one of three doses of LOKELMA or placebo administered once-daily for 28 days.
The primary endpoint in the randomized withdrawal phase was the mean serum potassium value over the period from Day 8 to Day 29, comparing LOKELMA treated and placebo treated patients.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.
PRESCRIBING INFORMATION
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