Drug Trials Snapshot: VELTASSA
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 the VELTASSA Prescribing Information for complete information.
VELTASSA (patiromer)
(vel-TAS-sa)
Relypsa, Inc.
Approval date: October 21, 2015
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
VELTASSA is a drug that is used to treat hyperkalemia. Hyperkalemia is a serious condition in which the amount of potassium in the blood is too high.
How is this drug used?
VELTASSA is a powder that is mixed with water, and taken once a day with food.
VELTASSA binds to many other drugs taken by mouth (orally administered). This can decrease the absorption and reduce the effects of those drugs. Therefore, VELTASSA and any other orally administered drug should be taken at least six hours apart.
What are the benefits of this drug?
VELTASSA reduced high levels of potassium in the blood and maintained the potassium at a normal level.
What are the benefits of this drug (results of trials used to assess efficacy)?
Results for the Part A primary endpoint, the change in serum potassium from baseline to Week 4 of treatment, are summarized in Table 2.
Table 2. Primary Endpoint Results for Part A of the Clinical Trial
| Baseline Potassium | Overall Population (n=237) |
||
|---|---|---|---|
| 5.1 to 5.5="" meq/l=""> (n=90) |
5.5 to 6.5="" meq/l=""> (n=147) |
||
| Serum Potassium (mEq/L) | |||
| Baseline, mean (SD) | 5.31 (0.57) | 5.74 (0.40) | 5.58 (0.51) |
| Week 4 Change from Baseline, Mean ( 95% CI) |
-0.65 (-0.74, -0.55) |
-1.23 (-1.31, -1.16) |
-1.01 (-1.07, -0.95) |
| p-value | > | ||
VELTASSA Prescribing Information, Table 2
The primary endpoint in Part B was the change in serum potassium from the Part B baseline to the earliest visit at which the patient’s serum potassium was first outside of the range of 3.8 to 5.5="" meq/l,="" or="" to="" part="" b="" week="" 4="" if="" the="" patient’s="" serum="" potassium="" remained="" in="" the="" range.="" results="" are="" summarized="" in="" table="">
Table 3. Primary Endpoint Results for Part B of the Clinical Trial
| Placebo (n=52) |
Veltassa (n=55) |
Difference | ||
|---|---|---|---|---|
| Estimate (95% CI) | p - value | |||
| Estimated Median Change in Serum Potassium from Baseline (mEq/L) | 0.72 | 0.00 | 0.72 (0.46, 0.99) |
> |
VELTASSA Prescribing Information, Table 3
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
Subgroup analyses were conducted for sex and age.
- Sex: VELTASSA was similarly effective in men and women.
- Race: The majority of subjects were white. Differences in response to VELTASSA among races could not be determined.
- Age: VELTASSA was similarly effective in patients below and above 65 years of age.
The tables below summarize efficacy results for Part A and Part B of the clinical trial, by subgroup.
Table 4. Primary Efficacy Endpoint, Part A, by Subgroup
| Subgroup | Total Patients 5.1 to 6.5=""> N=237 |
|||
|---|---|---|---|---|
| n | Mean | 95% CI | p-value | |
| Sex Male Female |
136 101 |
-0.93 -1.12 |
(-1.01, -0.84) (-1.21, -1.02) |
0.001> > |
| Age (years) 65> ≥65 |
111 126 |
-0.96 -1.01 |
(-1.05, -0.88) (-1.10, -0.92) |
0.001> > |
Clinical Trial Data
Table 5. Primary Efficacy Endpoint, Part B, by Subgroup
| Subgroup | Difference in Median Change (mEq/L) | ||||
|---|---|---|---|---|---|
| n (%) | Estimates | 95% CI | p-value | Interaction p-value | |
| Sex Male Female |
48 (54) 49 (46) |
0.70 0.83 |
(0.36, 1.04) (0.41, 1.24) |
0.001> > |
0.63 |
| Age (years) 65> ≥65 |
47 (44) 60 (56) |
0.57 0.81 |
(0.11, 1.03) (0.49, 1.14) |
0.006 > |
0.37 |
Clinical Trial Data
What are the possible side effects?
The most common side effects of VELTASSA are constipation, diarrhea, nausea, stomach-area discomfort, and gas.
VELTASSA can cause low levels of magnesium in your blood (hypomagnesemia).
Table 6 summarizes the most common adverse reactions in patients treated with VELTASSA in clinical trials.
Table 6. Adverse Reactions Reported in ≥2% of Patients
| Adverse Reactions | Patients treated with VELTASSA (N=666) |
| Constipation | 7.2% |
| Hypomagnesemia | 5.3% |
| Diarrhea | 4.8% |
| Nausea | 2.3% |
| Abdominal discomfort | 2.0% |
| Flatulence | 2.0% |
VELTASSA Prescribing Information, Table 1
Were there any differences in side effects among sex, race and age?
Subgroup analyses were conducted for sex and age.
- Sex: The risk of side effects was similar in men and women.
- Race: Most patients in the trial were white. Differences in side effects among races could not be determined.
- Age: The risk of gastrointestinal (related to the stomach and the intestines) side effects in patients age 65 and older was higher compared to patients below 65.
The table below summarizes gastrointestinal adverse events, by subgroup, for the 4 pooled clinical trials.
Table 7. Subgroup Analysis of Overall Treatment-Emergent Gastrointestinal Adverse Events
Subgroup |
VELTASSA (N=666) |
Placebo (N=49) |
||
|---|---|---|---|---|
| Overall Treatment -Emergent Gastrointestinal Adverse Events | 113 | 17% | 2 | 4.1% |
|
Sex |
||||
|
Male |
64 | 16% | 2 | 5.9% |
|
Female |
49 | 18.4% | 0 | 0.0% |
|
Age Group |
||||
|
17 - 64 years |
29 | 10.8% | 1 | 7.1% |
|
>=65 years |
84 | 21.1% | 1 | 2.9% |
|
Race |
||||
|
White |
110 | 16.7% | 1 | 2.1% |
|
Black or African American |
3 | 75% | 1 | 100% |
Clinical Trial Data
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
The FDA approved VELTASSA based on evidence from multiple trials, including a main clinical trial that included 243 patients with hyperkalemia. The main clinical trial was conducted at 71 sites in 10 countries, including United States and 9 European countries.
The side effect profile of VELTASSA was supported by the main clinical trial as well as three additional clinical trials (Phase 2 trials). The demographics of the 4 combined trials, which included a total of 715 patients (666 received VELTASSA and 49 received placebo), are summarized below.
Figure 1 summarizes how many men and women were enrolled.
Figure 1. Baseline Demographics by Sex
Clinical Trial Data
Figure 2 and Table 1 summarize the percentage of patients by race.
Figure 2. Baseline Demographics by Race
Clinical Trial Data
Table 1. Demographics of Efficacy Trials by Race
| Race | Number of Patients | Percentage |
|---|---|---|
| White | 708 | 99% |
| Black or African American | 5 | 0.7% |
| Asian | 1 | 0.1% |
| Native Hawaiian or other Pacific Islander | 1 | 0.1% |
Clinical Trial Data
Figure 3 summarizes the percentage of patients by age.
Figure 3. Baseline Demographics by Age
Clinical Trial Data
The table below summarizes the baseline demagraphics for the 4 pooled clinical trials that supported the safety profile of VELTASSA.
Table 8. Baseline Demographics for the Pooled Clinical Trials (Safety Population)
| Demographic Subgroup | VELTASSA (N=666) |
Placebo (N=49 ) |
Total (N=715) |
|||
|---|---|---|---|---|---|---|
| Sex, n (%) | ||||||
| Male | 400 | 60% | 34 | 69% | 434 | 60.7% |
| Female | 266 | 40% | 15 | 31% | 281 | 39.3% |
| Age Group, n (%) | ||||||
| 17 - 64 years | 268 | 40% | 14 | 28.6% | 282 | 39.4% |
| >=65 years | 398 | 60% | 35 | 71.4% | 433 | 60.6% |
| Race, n (%) | ||||||
| White | 660 | 99% | 48 | 98% | 708 | 99% |
| Black or African American | 4 | 0.6% | 1 | 2.0% | 5 | 0.7% |
| Asian | 1 | 0.2% | 0 | 0 | 1 | 0.1% |
| American Indian or Alaska Native | 1 | 0.2% | 0 | 0 | 1 | 0.1% |
| Ethnicity, n (%) | ||||||
| Hispanic or Latino | 8 | 1.2% | 0 | 0 | 8 | 1.1% |
| Not Hispanic or Latino | 658 | 98.8% | 49 | 100.0% | 707 | 98.9% |
Clinical Trial Data
How were the trials designed?
The main trial consisted of two parts (referred to as Part A and B).
In Part A, each patient was given VELTASSA. The dose was increased as needed until the potassium level decreased to a normal range.
In Part B, those patients whose potassium became normal with treatment using VELTASSA were then randomly assigned to either continue VELTASSA or switch to a placebo. The patients did not know which treatment they were getting. The potassium level of those continuing VELTASSA was compared to those now receiving a placebo.
The efficacy of VELTASSA was demonstrated in a two-part, single-blind randomized withdrawal study that evaluated VELTASSA in hyperkalemic patients with chronic kidney disease on stable doses of at least one renin-angiotensin-aldosterone system (RAAS) inhibitor .
In Part A, patients were treated with Veltassa for 4 weeks. Patients with a baseline serum potassium of 5.1 mEq/L to 5.5="" meq/l="" received="" a="" starting="" veltassa="" dose="" of="" 8.4="" grams="" per="" day="" (as="" a="" divided="" dose)="" and="" patients="" with="" a="" baseline="" serum="" potassium="" of="" 5.5="" meq/l="" to=""> 6.5="" meq/l="" received="" a="" starting="" dose="" of="" 16.8="" grams="" patiromer="" per="" day="" (as="" a="" divided="" dose).="" the="" dose="" of="" veltassa="" was="" titrated,="" as="" needed,="" based="" on="" the="" serum="" potassium="" level,="" assessed="" starting="" on="" day="" 3="" and="" then="" at="" weekly="" visits="" (weeks="" 1,="" 2="" and="" 3)="" to="" the="" end="" of="" the="" 4-week="" treatment="" period,="" with="" the="" aim="" of="" maintaining="" serum="" potassium="" in="" the="" target="" range="" (3.8="" meq/l="" to=""> 5.1="">
In Part B, patients with a Part A baseline serum potassium of 5.5 mEq/L to 6.5="" meq/l="" and="" whose="" serum="" potassium="" was="" in="" the="" target="" range="" (3.8="" meq/l="" to=""> 5.1="" meq/l)="" at="" part="" a="" week="" 4="" and="" still="" receiving="" raas="" inhibitor="" medication="" were="" randomized="" to="" continue="" veltassa="" or="" to="" receive="" placebo="" to="" evaluate="" the="" effect="" of="" withdrawing="" veltassa="" on="" serum="" potassium.="" the="" part="" b="" primary="" endpoint="" was="" the="" change="" in="" serum="" potassium="" from="" part="" b="" baseline="" to="" the="" earliest="" visit="" at="" which="" the="" patient’s="" serum="" potassium="" was="" first="" outside="" of="" the="" range="" of="" 3.8="" to=""> 5.5="" meq/l,="" or="" to="" part="" b="" week="" 4="" if="" the="" patient’s="" serum="" potassium="" remained="" in="" the="">
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