Compare Ceftazidime Avibactam + Metronidazole vs Meropenem for hospitalized adults with complicated Intra-Abdominal Infections

INTERVENTION: Product Name: ceftazidime avibactam Product Code: CAZ104 Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: CEFTAZIDIME PENTAHYDRATE CAS Number: 78439‐06‐2 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2000‐ INN or Proposed INN: avibactam CAS Number: 1192491‐61‐4 Current Sponsor code: NXL104 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ Pharmaceutical form of the placebo: Solution for injection/infusion Route of administration of the placebo: Intravenous use Trade Name: Metronidazole 500 mg / 100 ml Intravenous Infusion Product Name: metronidazole Pharmaceutical Form: Solution for injection/infusion INN or Proposed INN: METRONIDAZOLE CAS Number: 443‐48‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 500‐ Pharmaceutical form of the placebo: Solution for injection/infusion Route of administration of the placebo: Intravenous use Trade Name: Meronem Product Name: meropenem Pharmaceutical Form: Powder for solution for injection/infusion INN or Proposed INN: meropenem CAS Number: 119478‐56‐7 Other descriptive name: MEROPENEM TRIHYDRATE Concentration unit: g gram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Solution for injection/infusion Route of administration of the placebo: Intravenous use CONDITION: Complicated Intra‐Abdominal Infection (cIAI) ; MedDRA version: 17.0 Level: LLT Classification code 10056570 Term: Intra‐abdominal infection System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] PRIMARY OUTCOME: Main Objective: To assess the noninferiority of ceftazidime avibactam (CAZ104) plus metronidazole compared to meropenem alone with respect to clinical cure at the test‐of‐cure in patients who have at least 1 identified pathogen. Primary end point(s): To assess the proportion of patients with clinical cure in the microbiological modified intent‐to‐treat analysis set. Secondary Objective: To determine the efficacy of CAZ104 plus metronidazole compared to meropenem with respect to the clinical cure at the end of treatment with IV therapy (EOT) and at the late follow‐up (LFU); ; To determine the per‐patient and per‐pathogen microbiologic response of CAZ104 plus metronidazole compared to meropenem at EOT, TOC, and LFU; ; To evaluate the efficacy of CAZ104 plus metronidazole versus meropenem in; pathogens resistant to ceftazidime; ; To compare the time to first defervescence of CAZ104 plus metronidazole versus; meropenem; ; To evaluate the safety and tolerability profile of CAZ104 plus metronidazole; compared to meropenem; Timepoint(s) of evaluation of this end point: At the test of cure visit SECONDARY OUTCOME: Secondary end point(s): 1. To assess the proportion of patients with clinical cure in the ; microbiologically evaluable and extended microbiologically evaluable ; analysis sets. ; 2. To assess the proportion of patients with clinical cure in the ; microbiological modified intent‐to‐treat, microbiologically evaluable, and ; extended microbiologically evaluable analysis sets. ; 3. To assess the proportion of patients with clinical cure in the clinically ; evaluable anlaysis set. ; 4. To assess the proportion of patients with a favorable per‐patient ; microbiological response in the microbiological modified intent to treat, ; microbiologically evaluable, and extended microbiologically evaluable ; analysis sets. ; 5. To assess the proportion of favorable per‐pathogen microbiological ; response in the microbiological modified intent to treat, ; microbiologically evaluable, and extended microbiologically evaluable ; anlaysis sets. ; 6. To assess the favorable per‐pathogen microbiologic response by ; minimum inhibitory concentration (MIC) categories in the ; microbiological modified intent to treat, microbiologically evaluable, and ; extended microbiologically evaluable analysis sets. ; 7. To assess the favorable per‐patient clinical response and favorable per ; patient microbiological response for patients infected with ceftazidimeresistant ; pathogens in the microbiological modified intent to treat, ; microbiologically evaluable, and extended microbiologically evaluable ; analysis sets. ; 8. To assess the proportion of patients with a favorable per pathogen ; microbiological response for patients infected with ceftazidime‐resistant ; pathogens in the microbiological modified intent to treat, ; microbiologically evaluable, and extended microbiologically evaluable ; anlaysis sets. ; 9. To assess the time to first defervescence in the clinically evaluable, ; microbiologically evaluable, and extended microbiologically evaluable ; anlaysis sets for patients who have fever at study entry. ; 10. To assess the safety and tolerability by incidence and severity of ; adverse events and serious adverse events, vital signs, clinical ; laboratory tests, ECGs and physical exams. ; 11. Pharmacokinetics: maximum concentration (Cmax), minimum ; concentration, area under the plasma concentration time curve at steady ; state, and terminal half‐life Timepoint(s) of evaluation of this end point: 1. at the test of cure visit ; 2. at the end of treatment and late follow‐up visits ; 3. at the end of treatment, test of cure and late follow‐up visits ; 4. at the end of treatment, test of cure and late follow‐up visits ; 5. at the end of treatment, test of cure and late follow‐up visits ; 6. at the end of treatment, test of cure and late follow‐up visits ; 7. at the test of cure visit ; 8. at the test of cure visit ; 9. while on IV study therapy ; 10. study duration ; 11. Anytime within 15 minutes prior to or after stopping study drug, ; anytime between 30 and 90 minutes after stopping study drug, anytime ; between 300 minutes and 360 minutes after stopping study drug INCLUSION CRITERIA: 18 to 90 years of age inclusive ‐ Female patient is authorized to participate if at least one of the following criteria are met: (a) Surgical sterilization (b) Age =50 years and postmenopausal as defined byamenorrhea for 12 months or more following cessation of all exogenous hormonal treatments (c) Age <50 years and postmenopausal as defined by documented LH and FSH levels in the postmenopausal range PLUS amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments (d) Patient has a negative serum pregnancy test (serum ß‐human chorionic gonadotropin [ßhCG]) within 1 day prior to study entry, and agrees to use highly effective contraception methods during treatment and for at least 7 days after last dose of IV study therapy. ‐ Intraoperative/postoperative enrollment with confirmation (presence of pus within the abdominal cavity) of an intra‐abdominal infection associated with peritonitis