Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Ceftazidime- Avibactam · 3 trials · 3 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).
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.
| Arm | Type | Description |
|---|---|---|
| Ceftazidime - Avibactam ( CAZ-AVI) | EXPERIMENTAL | IV treatment |
| Best Available Therapy | ACTIVE_COMPARATOR | IV treatment |
| Doripenem | ACTIVE_COMPARATOR | IV treatment |
| 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 |
| 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 |
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 an investigational small molecule being developed for complicated urinary tract infections (cUTI) including acute pyelonephritis, and complicated intra-abdominal infections. It is a combination antibiotic studied in hospitalized adults and children with these serious bacterial infections.
Ceftazidime-Avibactam is being developed by Pfizer, Inc. (NYSE: PFE). The company is conducting clinical trials of the drug for complicated urinary tract infections and complicated intra-abdominal infections.
Ceftazidime-Avibactam is in Phase 3 clinical development. It is investigational and not yet approved. Two Phase 3 trials have been completed, along with a Phase 2 pediatric study, all with results reported.
Ceftazidime-Avibactam has completed two Phase 3 trials: NCT01595438 and NCT01599806, both comparing it to doripenem followed by oral therapy in hospitalized adults with complicated UTIs. A third Phase 3 trial, NCT01644643, studied the drug for infections due to ceftazidime-resistant pathogens. A Phase 2 trial, NCT02497781, evaluated it in children with cUTIs.
Ceftazidime-Avibactam is a combination of ceftazidime, a cephalosporin antibiotic, and avibactam, a beta-lactamase inhibitor. Avibactam protects ceftazidime from degradation by certain beta-lactamase enzymes, restoring its activity against resistant gram-negative bacteria.
Yes, Ceftazidime-Avibactam is also known as CAZ-AVI. In clinical trials, it is referred to by both names, including in the pediatric study NCT02497781, which evaluates the safety and efficacy of CAZ-AVI compared with cefepime.