Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Ceftazidime - Avibactam ( CAZ-AVI)
Ceftazidime-avibactam · 6 trials · 5 indications
Proportion of patients with clinical cure at the TOC visit in the mMITT analysis set. Clinical cure: Complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy (other than those allowed per protocol) is necessary; for cIAI patients no drainage or surgical intervention after 96 hours from randomization is necessary (ie. drainage or surgical intervention up to 96 hours from randomization is permissible).
The proportion of patients meeting the cure criteria: complete resolution or significant improvement of signs and symptoms of the index infection such that no further antibacterial therapy, drainage, or surgical intervention was necessary.
Number of patients with symptomatic resolution (or return to premorbid state) of UTI-specific symptoms except flank pain (frequency/urgency/dysuria/suprapubic pain) with resolution of or improvement in flank pain based on the patient-reported symptom assessment response at the Day 5 visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
Number of patients with both a favorable per patient microbiological response and symptomatic resolution (or return to premorbid state) of all UTI-specific symptoms (frequency/urgency/dysuria/suprapubic pain/flank pain) based on the patient-reported symptom assessment response at the TOC visit in the mMITT analysis set. The sponsor will conclude noninferiority if the lower limit of the 95% CI of difference (corresponding to a 97.5% 1-sided lower bound) is greater than -12.5% for both FDA coprimary outcome variables (symptomatic resolution at day 5 or favorable combined response at test of cure (TOC)).
Number of patients with a favorable per patient microbiological response at TOC. The primary efficacy outcome variable for ROW is the proportion of patients with a favorable per-patient microbiological response at the TOC visit in the mMITT analysis set.
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between first dose of study drug and up to late follow-up (LFU) visit (20 to 36 days after last dose of study treatment \[IV or oral\]) that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAE and non-SAE.
Percentage of participants with Cephalosporin class effects (defined as adverse event of special interest (AEoSI) within the safety topics (ST) of hypersensitivity/anaphylaxis) and additional AEs (which included AEs of diarrhea, renal disorder, hematological disorder and liver disorder relevant to the cephalosporin class within the safety topics (ST) based on MedDRA 20.0) were reported in this outcome measure.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Physical examination included an assessment of the following: general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, respiratory system, cardiovascular system, abdomen, musculoskeletal system (including spine and extremities), and neurological system. Participants with new or aggravated abnormal physical examination findings with regard to baseline findings were reported. Abnormality in physical examinations were based on blinded observer's discretion. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Criteria for potentially clinically significant laboratory abnormalities: hematology (platelets: \<0.4\*lower limit of normal \[LLN\], \>2\*upper limit of normal \[ULN\], \>40% decrease from baseline \[DFB\],\>100% Increase from baseline \[IFB\]; Chemistry (Bicarbonate: \<0.7\*LLN, \>1.3\*ULN, \>50% DFB, \>30% IFB).
PCS criteria for abnormal value of ECG parameters: QT interval \>=450 milliseconds (msec); 480 msec; \>=500 msec; Increase from baseline (IFB) of \>=30 msec; \>=60 msec and \>90 msec; Decrease from baseline (DFB) of \>=30 msec; \>=60 msec and \>90 msec. QT interval using Bazett's correction (QTcB): \>=450 milliseconds (msec); 480 msec; \>=500 msec; Increase from baseline (IFB) of \>=30 msec; \>=60 msec and \>90 msec; DFB of \>=30 msec; \>=60 msec and \>90 msec. QT interval using Fridericia's correction (QTcF): \>=450 msec; 480 msec; \>=500 msec; IFB of \>=30 msec; \>=60 msec and \>90 msec; DFB of \>=30 msec; \>=60 msec and \>90 msec. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
CrCl is a measure of glomerular filtration rate (GMFR), an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of participants with CrCl in the following categories were reported: \<30 mL/min/1.73 m\^2, \>=30 to \<50 mL/min/1.73 m\^2, \>=50 mL/min/1.73 m\^2 to \<80 mL/min/1.73 m\^2, and \>=80 mL/min/1.73 m\^2.
CrCl is a measure of glomerular filtration rate (GMFR), an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of participants with CrCl in the following categories were reported: \<30 mL/min/1.73 m\^2, \>=30 to \<50 mL/min/1.73 m\^2, \>=50 mL/min/1.73 m\^2 to \<80 mL/min/1.73 m\^2, and \>=80 mL/min/1.73 m\^2. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
CrCl is a measure of glomerular filtration rate (GMFR), an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of participants with CrCl in the following categories were reported: \<30 mL/min/1.73 m\^2, \>=30 to \<50 mL/min/1.73 m\^2, \>=50 mL/min/1.73 m\^2 to \<80 mL/min/1.73 m\^2, and \>=80 mL/min/1.73 m\^2. TOC visit occurred within 8 to 15 days after last dose of any study drug (IV or oral).
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
Physical examination included an assessment of the following: general appearance, skin, head and neck (including ears, eyes, nose and throat), lymph nodes, thyroid, respiratory system, cardiovascular system, abdomen, musculoskeletal system (including spine and extremities), and neurological system. Participants with new or aggravated abnormal physical examination findings with regard to baseline findings were reported. Abnormality in physical examinations were based on blinded observer's discretion. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
ECG parameters included maximum QT intervals using Fridericia's correction (QTcF). Maximum QTcF \>450 millisecond (ms); maximum QTcF \>480 ms; and maximum QTcF \>500 ms. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
CrCl is a measure of GMFR, an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of participants with CrCl in the following categories were reported: \<30 mL/min/1.73 m\^2, \>=30 to \<50 mL/min/1.73 m\^2, \>=50 mL/min/1.73 m\^2 to \<80 mL/min/1.73 m\^2, and \>=80 mL/min/1.73 m\^2. EOIV visit occurred within 24 hours after completion of last infusion of the study drug.
CrCl is a measure of GMFR, an index of kidney function. It is the volume of blood plasma that is cleared of creatinine by the kidneys per unit time. Percentage of participants with CrCl in the following categories were reported: \<30 mL/min/1.73 m\^2, \>=30 to \<50 mL/min/1.73 m\^2, \>=50 mL/min/1.73 m\^2 to \<80 mL/min/1.73 m\^2, and \>=80 mL/min/1.73 m\^2. LFU visit occurred within 20 to 35 days after last dose of study treatment (IV or oral).
| Arm | Type | Description |
|---|---|---|
| Ceftazidime - Avibactam ( CAZ-AVI) | EXPERIMENTAL | IV treatment |
| Best Available Therapy | ACTIVE_COMPARATOR | IV treatment |
| Ceftazidime-Avibactam plus metronidazole | EXPERIMENTAL | - |
| Meropenem | ACTIVE_COMPARATOR | - |
| Doripenem | ACTIVE_COMPARATOR | IV treatment |
| ceftazidime-avibactam (CAZ-AVI) | EXPERIMENTAL | CAZ-AVI to be administered every 8 hours as a 2-hour infusion (CAZ-AVI dose and frequency of IV administration will depend upon body weight and renal function) |
| Cefepime | ACTIVE_COMPARATOR | Patients randomised to receive cefepime should receive the dose, schedule and infusion duration as recommended in the local prescribing information or as prescribed by the investigator. The maximum dose of cefepime in any single infusion should not exceed 2000 mg |
| CAZ-AVI and metronidazole | EXPERIMENTAL | CAZ-AVI to be administered every 8 hours as a 2 hour infusion (CAZ-AVI dose and frequency of IV administration will depend upon body weight and renal function) followed by metronidazole (no later than 30 minutes after CAZ-AVI infusion ) to be administered every 8 hours as 20 to 30 minutes infusion |
| Name | Type | Description |
|---|---|---|
| Ceftazidime - Avibactam ( CAZ-AVI) | DRUG | Ceftazidime 2000 mg and 500 mg of avibactam Patients randomized to receive CAZ-AVI will receive an infusion of CAZ-AVI (2000 mg ceftazidime and 500 mg avibactam) every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 120 minutes |
| Best Available Therapy | DRUG | Patients randomized to receive Best Available Therapy will receive the best available standard of care (SOC) anti-infective therapy for their infection administered in accord with approved local label recommendation |
| Metronidazole | DRUG | Anti-infective, 500 mg (cIAI only) Patients randomized to receive CAZ-AVI for cIAI will also receive metronidazole (500 mg) administered by IV infusion in a volume of 100 mL at a constant rate over 60 minutes immediately following the CAZ-AVI infusion |
| Ceftazidime-avibactam | DRUG | Ceftazidime-Avibactam powder for concentrate for solution for infusion 2000 mg/500 mg |
| Meropenem | DRUG | Meropenem powder for solution for infusion 1000mg |
| Doripenem | DRUG | 500 mg of Doripenem. Patients randomized to receive Doripenem will receive an infusion of Doripenem 500 mg every 8 hours administered by intravenous (IV) infusion in a volume of 100 mL at a constant rate over 60 minutes |
| Either switch to oral therapy: 500 mg of Ciprofloxacin (oral) | DRUG | Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement |
| or switch to oral therapy: 800 mg/160 mg of sulfamethoxazole/trimethoprim (oral) | DRUG | Patients are eligible for oral switch after receiving 5 full days of IV therapy and have met protocol specified criteria for clinical improvement |
| Ceftazidime -avibactam | DRUG | Patients randomised (3:1) to the CAZ-AVI or cefepime treatment |
| Cefepime | DRUG | Patients randomised (3:1) to the CAZ-AVI or cefepime treatment |
Inclusion Criteria: * Patient must be ≥18 and ≤90 years of age * Female patients can participate if they are surgically sterile or completed menopause or females capable of having children and agree not to attempt pregnancy while receiving IV study therapy and for a period of 7 days after * Patient...
Ceftazidime-avibactam is used to treat complicated intra-abdominal infections and complicated urinary tract infections, including acute pyelonephritis. It is also studied for infections caused by ceftazidime-resistant pathogens. It is a small-molecule antibacterial developed by Pfizer, Inc. (PFE) for infectious disease indications.
Ceftazidime-avibactam is developed by Pfizer, Inc., which trades on the New York Stock Exchange under the ticker PFE. Pfizer is the company responsible for the clinical development program of this antibacterial agent.
Ceftazidime-avibactam is in Phase 3 clinical development. The program includes completed Phase 2 and Phase 3 trials. It is an investigational product and has not been approved by the FDA for the studied indications.
Ceftazidime-avibactam has been evaluated in completed trials including NCT01726023, a Phase 3 study in adults with complicated intra-abdominal infections, NCT01644643, a Phase 3 study in infections due to ceftazidime-resistant pathogens, and two Phase 2 pediatric trials, NCT02497781 and NCT02475733.
Yes, ceftazidime-avibactam is also known as CAZ-AVI, which is an abbreviation for the combination. Other spelling variants include ceftazidime -avibactam and ceftazidime - Avibactam (CAZ-AVI). These names refer to the same investigational antibacterial agent.
Across the reported clinical trials, 1,239 patients have been enrolled in studies of ceftazidime-avibactam. The trials were randomized, double-blind, and active-controlled, evaluating the agent in complicated intra-abdominal infections and complicated urinary tract infections.