Drugs

Drug Trial Snapshot: Zurampic

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 ZURAMPIC Prescribing Information for complete information.

ZURAMPIC (lesinurad)
(zer-AM-pik)
AstraZeneca
Approval date: December 22, 2015


DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

ZURAMPIC is a drug for lowering uric acid levels in the blood of adult patients with gout who were not able to achieve desired levels using other drugs for lowering uric acid called xanthine oxidase inhibitors (which includes allopurinol and febuxostat). ZURAMPIC is to be used together with xanthine oxidase inhibitor drug.

How is this drug used?

ZURAMPIC is a tablet taken once a day together with xanthine oxidase inhibitor drug such as allopurinol or febuxostat.

What are the benefits of this drug?

ZURAMPIC with a xanthine oxidase inhibitor drug lowered uric acid levels more than placebo with a xanthine oxidase inhibitor drug.

What are the benefits of this drug (results of trials used to assess efficacy)?

Tables below summarize efficacy results for the clinical trials.

Table 2. Proportion of Patients Achieving Target Serum Uric Acid Levels (< 6 mg/dL) in Two Studies of ZURAMPIC in Combination with Allopurinol

TrialTimepointPatients Achieving Serum Uric Acid TargetDifference of Proportion (95% C.I.)
Placebo + AllopurinolZURAMPIC + AllopurinolZURAMPIC vs. Placebo
Trial 1 (N=603)Month 628%54%0.26 ( 0.17, 0.36)
Trial 2 (N=610)Month 623%55%0.32 (0.23, 0.41)

ZURAMPIC Prescribing Information

Table 3. Proportion of Patients Achieving Target Serum Uric Acid Levels (< 5 mg/dL) in Trial 3 with ZURAMPIC in Combination with Febuxostat in Tophaceous Gout

 Patients Achieving Serum Uric Acid TargetDifference of Proportion (95% C.I.)
TimepointPlacebo + FebuxostatZURAMPIC + FebuxostatZURAMPIC vs. Placebo
Month 647%57%0.10 (-0.03, 0.23)

ZURAMPIC Prescribing Information

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

  • Sex: The majority of patients in the clinical trials were men. Differences in response to ZURAMPIC between sexes could not be determined.
  • Race: ZURAMPIC worked similarly among White, Black, and Asian patients. Differences among other races could not be determined due to small number of patients.
  • Age: ZURAMPIC worked similarly in patients below and above 65 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age?

Figure 4 summarizes results from Trials 1 and 2 for the primary efficacy endpoint, the proportion of subjects with a serum uric acid level below 6.0 mg/dL at month 6, by age, sex, race, and ethnicity. Data is provided combining the allopurinol background Trials 1 and 2 to gain precision of characterization and power of comparison and because the designs of Trials 1 and 2 were nearly identical. Results from statistical tests assessing whether the treatment effect varied across subgroups are also provided.

Figure 4: Difference (95% Confidence Interval) of Proportion for Subjects with Month 6 sUA Levels < 6.0 mg/dL (Pooled Trials 1 and 2: ZURAMPIC Minus Placebo, Non-Responder Imputation)

Figure summarizes efficacy results by subgroup)

sUA: serum uric acid; Diff: Difference in proportion; LCL: lower confidence limit; UCL: upper confidence limit; p-value: statistical test measuring whether the treatment effect differs across subgroups (i.e., p-value for treatment-by-subgroup interaction); F: female; M: Male; LESU: lesinurad (Zurampic)

FDA Statistical review

Figure 5 summarizes results from Trial 3 for the primary efficacy endpoint, the proportion of subjects with a serum uric acid level below 5.0 mg/dL at month 6, by age, sex, race, and ethnicity.

Figure 5: Difference (95% Confidence Interval) of Proportion for Subjects with Month 6 sUA Levels < 5.0 mg/dL (Trial 3: ZURAMPIC minus Placebo, Non-Responder Imputation)

Figure summarizes efficacy results by subgroup)

sUA: serum uric acid; Diff: Difference in proportion; LCL: lower confidence limit; UCL: upper confidence limit; p-valule: statistical test measuring whether the treatment effect differs across subgroups (i.e., p-value for treatment-by-subgroup interaction); F: female; M: Male; LESU: lesinurad (Zurampic)

FDA Statistical review

What are the possible side effects?

The most common side effects of ZURAMPIC are headache, flu, higher levels of blood creatinine (a measure of kidney function) and heart burn.

Some patients taking ZURAMPIC may develop serious kidney problems such as sudden decrease in kidney function (acute kidney failure).

What are the possible side effects (results of trials used to assess safety)?

The table below summarizes adverse reactions that occurred at a rate of at least 2% and at a higher rate in the ZURAMPIC group than the placebo group.

Table 4. Adverse Reactions Occurring in ≥ 2% of ZURAMPIC 200 mg-Treated Patients and at Least 1% Greater than Seen in Patients Receiving Placebo in Controlled Studies with ZURAMPIC in Combination with a Xanthine Oxidase Inhibitor (XOI)

Adverse ReactionPlacebo + XOI
(N=516)
ZURAMPIC 200 mg + XOI
(N=511)
Headache4.1%5.3%
Influenza2.7%5.1%
Gastroesophageal reflux disease0.8%2.7%

ZURAMPIC Prescribing Information

The table below summarizes renal adverse reaction in clinical trials with ZURAMPIC.

Table 5. Incidence of Renal-Related Adverse Reactions and Nephrolithiasis in Placebo-Controlled Clinical Studies with ZURAMPIC in Combination with a Xanthine Oxidase Inhibitor (XOI)

Adverse ReactionPlacebo + XOI
(N=516)
n(%)
ZURAMPIC 200 mg + XOI
(N=511)
n(%)
Blood creatinine increased12 (2.3%)22 (4.3%)
Renal failure111 (2.1%)6 (1.2%)
Nephrolithiasis9 (1.7%)3 (0.6%)

1Renal failure includes the following adverse reactions: renal failure, renal impairment, renal failure chronic, renal failure acute, acute pre-renal failure.

ZURAMPIC Prescribing Information

At doses greater than 200 mg a day of ZURAMPIC with an XOI, the risk of renal-related adverse events and nephrolithiasis was higher and should not be used.

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 all races studied.
  • Age: The risk of side effects was similar in patients below and above 65 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

The table below summarizes treatment emergent adverse events (TEAEs) by subgroup for the pooled clinical trials.

Table 6. Subgroup Analysis of TEAEs

SubgroupPlacebo + XOI
(N=516)
ZURAMPIC + XOI
(N=511)
Sex
Male346/492 (70%)367/489 (75%)
Female17/24 (71%)19/22 (86%)
Age Group
17 - 64 years308/443 (70%)338/454 (74%)
>=65 years55/73 (75%)48/57 (84%)
Race
White282/402 (70%)301/398 (76%)
Black or African American39/59 (66%)40/60 (67%)
Asian17/30 (57%)24/27 (89%)
American Indian or Alaska Native2/2 (100%)4/4 (100%)
Native Hawaiian or Other Pacific Islander10/10 (100%)5/8 (63%)
Maori1/1 (100%)3/4 (75%)
Other12/12 (100%)9/10 (90%)

Clinical trial data

WHO WAS IN THE CLINCAL TRIALS?

Who participated in the clinical trials?

The FDA approved ZURAMPIC based on evidence from three clinical trials of patients with high uric acid blood levels and gout. The trials were conducted in the United States, Canada, Belgium, Switzerland, Germany, Spain, Poland, Ukraine, Australia, New Zealand and South Africa.

The figure below summarizes how many men and women were in the clinical trials. 

Figure 1. Baseline Demographics by Sex

Pie chart summarizing how many men and women were in the clinical trials of the drug ZURAMPIC . In total, 981 men (96%) and 46 women (4%) participated in the clinical trials.

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

Pie chart summarizing the percentage of patients by race in ZURAMPIC clinical trials. In total, 800 Whites (78%), 119 Blacks (12%), 57 Asians (5%), 18 Native Hawaiian or other Pacific Islander (2%) and 33 all other races combined (3%), participated in the clinical trials.) Clinical trial data 

Table 1. Baseline Demographics by Race

RaceNumber of PatientsPercentage
White80078%
Black or African American11912%
Asian575%
Native Hawaiian or Other Pacific Islander182%
American Indian or Alaska Native6less than 1%
Maori5less than 1%
Other222%

Clinical trial data

Figure 3 summarizes the percentage of patients by age in the clinical trials.

Figure 3. Baseline Demographics by Age

Pie charts summarizing how many individuals of certain age groups were in the clinical trials. In total, 897 were younger than 65 years (87%), and 130 patients were 65 years and older (13%).)

Clinical Trial Data

Who participated in the trials?

Table 7 Baseline Demographics of Patients in the Clinical Trials

Demographic Parameters

Placebo + XOI
(N=516)

ZURAMPIC + XOI
(N=511)

Total
(N=1027)

Sex

Men

492 (95.3)

489 (95.7)

981 (95.5)

Women

24 (4.7)

22 (4.3)

46 (4.5)

Age 

Mean years (SD)

52.2 (11.13)

51.9 (10.98)

52.1 (11.05)

Median (years)

52.0

52.0

52.0

Min, Max (years)

21, 81

21, 82

21, 82

Age Group

below 65 years

443 (85.9)

454 (88.8)

897 (87.3)

65 and above

73 (14.1)

57 (11.2)

130 (12.7)

Race

White

402 ( 77.9)

398 ( 77.9)

800 (77.9)

Black or African American

59 (11.4)

60 (11.7)

119 (11.6)

Asian

30 (5.8)

27 (5.3)

57 (5.6)

American Indian or Alaska Native

2 (0.4)

4 (0.8)

6 (0.6)

Native Hawaiian or Other Pacific Islander

10 (1.9)

8 (1.6)

18 (1.8)

Maori

1 (0.2)

4 (0.8)

5 (0.5)

Other

12 (2.3)

10 (2.0)

22 (2.1)

Region

United States

387 (75.0)

390 (76.3)

777 (75.7)

European Union

58 (11.2)

51 (10.0)

109 (10.6)

Other

71 (13.8)

70 (13.7)

141 (13.7)

Clincal Trial Data

How were the trials designed?

ZURAMPIC was approved by the FDA based on three clinical trials. All patients had gout and high uric acid not well controlled with their other medications (allopurinol or febuxostat). In the first two trials patients were randomly assigned to ZURAMPIC plus allopurinol or placebo plus allopurinol. In the third trial patients were randomly assigned to ZURAMPIC plus febuxostat or placebo plus febuxostat. Neither the patients nor the health care professionals knew which patients were in which group until after the drug trial was complete. Patients were evaluated for improvement in uric acid levels after 6 months, but they stayed on the medications for total of 12 months.

How were the trials designed?

ZURAMPIC was studied in 3 multicenter, randomized, double-blind, placebo-controlled clinical trials in adults. Patients had to have hyperuricemia and gout while receiving a treatment with a xanthine oxidase inhibitor, allopurinol (for Trials 1 and 2) or febuxostat (for Trial 3). All trials were of 12 months duration and patients received prophylaxis for gout flares with colchicine or non-steroidal anti-inflammatory drugs (NSAIDs) during the first 5 months of ZURAMPIC treatment.

The primary endpoint was the proportion of patients achieving target serum uric acid levels (< 6 mg/dL for Trials 1 and 2, and < 5 mg/dL for Trial 3) at Month 6.

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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Page Last Updated: 04/01/2016
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