Drug Trials Snapshot: AVYCAZ (cUTI)
For the treatment of complicated urinary tract infections
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the clinical trials that support 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 AVYCAZ Prescribing Information for complete information.
AVYCAZ (ceftazidime-avibactam)
(Av-EE-Kaz)
Forest Pharmaceuticals, Inc.
Approval Date: February 25, 2015
DRUG TRIALS SNAPSHOT SUMMARY:
What is the drug for?
AVYCAZ is a drug used to treat adults who have a serious infection in their urinary tract system called a complicated urinary tract infection (abbreviated as cUTI). It should be used only when few or no other treatment options are available. AVYCAZ is also approved for patients with a serious infection in their belly called a complicated intra-abdominal infection. This is discussed in a separate Snapshot.
AVYCAZ is a combination of two drugs: ceftazidime, a previously-approved drug that fights bacteria (antibiotic) and avibactam, a new drug that improves how ceftazidime works.
How is this drug used?
AVYCAZ is a drug administered by a health care professional directly into the bloodstream though a needle in the vein. This is known as an intravenous, or IV, infusion.
What are the benefits of this drug?
In patients who have few or no other treatment options, AVYCAZ would be expected to help improve symptoms of cUTI.
What are the benefits of this drug (results of trials used to assess efficacy)?
The determination of efficacy of AVYCAZ was supported in part by the previous findings of the efficacy of ceftazidime for the treatment of cUTI. The contribution of avibactam to AVYCAZ was primarily established in vitro and in animal models of infection. AVYCAZ was studied in a Phase 2, randomized, blinded, active-controlled, multicenter trial in adults with cUTI. The trial was not designed with any formal hypothesis for inferential testing against the active comparator.
Were there any differences in how well the drug worked in clinical trials among sex, race and age?
The studies that looked at benefit of AVYCAZ were too small to determine if there were differences in sex, race, and age subgroups.
Were there any differences in how well the drug worked in clinical trials among sex, race and age groups?
There are currently limited data on the efficacy of AVYCAZ. Therefore, subgroup analysis for efficacy cannot be performed.
What are the possible side effects?
In patients treated for cUTI, the most common side effects were constipation, anxiety, and abdominal pain.
Severe allergic reactions can occur. Patients who are allergic to penicillin may also be allergic to AVYCAZ.
Serious side effects, such as seizures and coma, can occur more frequently in patients whose kidneys do not work as well as they should. These are known effects of the ceftazidime component of AVYCAZ.
What are the possible side effects (results of trials used to assess safety)?
Table 2 summarizes the most common adverse events observed in the trial.
Table 2. Incidence of Selected Adverse Reactions Occurring in 5% or More of Patients Receiving AVYCAZ in the Trial
| Adverse Event | AVYCAZ (N = 68) | Imipenem-Cilastatin (N = 67) |
|---|---|---|
| Nausea | 2% | 5% |
| Constipation | 10% | 3% |
| Abdominal pain | 7% | 5% |
| Upper abdominal pain | 7% | 2% |
| Increased blood alkaline phosphatase | 3% | 2% |
| Increased alanine aminotransferase | 3% | 6% |
| Dizziness | 6% | 0% |
| Anxiety | 10% | 8% |
Source: Extracted from AVYCAZ Package Insert, Section 6, Table 4
Were there any differences in side effects among sex, race and age?
Subgroup analyses were conducted for sex, race and age.
- Sex: The number of patients in the trial was small and the majority were female. There did not appear to be clinically meaningful differences in the frequency of side effects between men and women.
- Race: The number of patients in the non-white subgroup was limited. Therefore, differences among races could not be determined.
- Age: The number of patients above 65 years of age was limited. Therefore, differences between those above and below 65 years of age could not be determined.
Were there any differences in side effects of the clinical trials among sex, race and age groups?
The table below summarizes the incidence of treatment-emergent adverse events in the clinical trial by subgroup.
Table 3. Summary of Incidence of Treatment-Emergent Adverse Events by Subgroup (Safety Population)
| Subgroup | AVYCAZ (N = 68) n/N (%) | Imipenem-Cilastatin (N = 67) n/N (%) |
|---|---|---|
Overall Response/All patients | 47/68 (69.1) | 52/67 (77.6) |
| Sex | ||
| Male | 10/17 (58.8) | 14/18 (77.8) |
| Female | 37/51 (72.5) | 38/49 (77.6) |
| Age Group | ||
| 17 to 64 years | 41/57 (71.9) | 42/55 (76.4) |
| >=65 years | 6/11 (54.5) | 10/12 (83.3) |
| >=75 years | 3/6 (50) | 9/10 (90.0) |
| Race | ||
| White | 28/40 (70) | 32/41 (78.0) |
| Black or African American | 1/2 (50) | 4/5 (80.0) |
| Asian | 4/8 (50) | 3/5 (60.0) |
| Other | 14/18 (77.8) | 13/16 (81.3) |
Source: Extracted from Company’s Submission
WHO WAS IN THE CLINICAL TRIALS?
Who participated in the clinical trials?
FDA approved AVYCAZ based on the prior approval and known benefit of ceftazidime as well as more recent evidence from the laboratory and from a clinical trial of AVYCAZ in 135 patients with cUTI. The trial included patients from the United States, South America, and Asia.
Figure 1 summarizes how many men and women were enrolled in the clinical trial to evaluate safety.
Figure 1. Baseline Demographics by Sex (Safety)
Source: From Clinical Reviewer
Figure 2 and Table 1 summarize the percentage of patients by race enrolled in the clinical trials to evaluate safety.
Figure 2. Baseline Demographics by Race (Safety)
Source: From Clinical Reviewer
Table 1. Baseline Demographics by Race (Safety Population)
| Race | Number of Patients | Percentage (%) |
|---|---|---|
| White | 81 | 85.3 |
| Black / African American | 7 | 7.4 |
| Asian | 13 | 13.7 |
| Other | 34 | 35.8 |
Source: From Clinical Reviewer
Figure 3 summarizes how many patients by age were enrolled in the clinical trial to assess safety.
Figure 3. Baseline Demographics by Age (Safety Population)
Source: From Clinical Reviewer
Who participated in the trials?
The table below summarizes baseline demographic information for the safety population.
Table 4. Demographic and Baseline Characteristics (Safety Population)
| Demographic Parameter | AVYCAZ N=68 n (%) | Imipenem- Cilastatin N=67 n (%) |
|---|---|---|
| Sex | ||
| Male | 17 (25) | 18 (26.9) |
| Female | 51 (75) | 49 (73.1) |
| Age (years) | ||
| Mean (SD) | 46.4 (18.2) | 49.9 (18.4) |
| Median | 47.5 | 51 |
| Min, Max | 18, 85 | 18, 89 |
| Age Group | ||
| 17 to 64 years | 57 (83.8) | 55 (82.1) |
| >=65 years | 11 (16.2) | 12 (17.9) |
| >=75 years | 6 (8.8) | 10 (14.9) |
| Race | ||
| White | 40 (58.8) | 41 (61.2) |
| Black or African American | 2 (2.9) | 5 (7.5) |
| Asian | 8 (11.8) | 5 (7.5) |
| Other | 18 (26.5) | 16 (23.9) |
| Region | ||
| United States | 11 (16.2) | 9 (13.4) |
| South America | 16 (23.5) | 17 (25.4) |
| Asia | 41 (60.3) | 41 (61.2) |
Source: From Clinical Reviewer
How were the trials designed?
In the clinical trial, half of the patients were chosen at random to receive AVYCAZ, and the other half was given another antibiotic called imipenem-cilastatin. Neither the patients nor the health care professionals administering the drug knew which patients were taking AVYCAZ and which were taking imipenem-cilastatin until after the study was complete.
How were the trials designed?
The trial was a Phase 2, prospective, multicenter, investigator-blinded, randomized trial to evaluate the efficacy, safety, and tolerability of AVYCAZ versus imipenem-cilastatin in the treatment of adults with cUTI. Patients were stratified based on the presence or absence of pyelonephritis and randomized 1:1 to either drug. Switch to oral therapy (ciprofloxacin 500 mg orally every 12 hours) was allowed after completion of at least 4 days of therapy. The total duration of therapy was 7 to 14 days.
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
MEDICAL REVIEW