Study to Assess Efficacy and Safety of PF-06947386 in Japanese Adult Patients With Complicated Intra-abdominal Infection

A PHASE 3, MULTICENTER, OPEN-LABEL, SINGLE-ARM STUDY TO ASSESS THE EFFICACY AND SAFETY OF CEFTAZIDIME-AVIBACTAM (PF-06947386) PLUS METRONIDAZOLE IN JAPANESE ADULT PATIENTS WITH COMPLICATED INTRA-ABDOMINAL INFECTION REQUIRING HOSPITALIZATION

Study C3591036 is a Phase 3 study to assess the efficacy and safety of PF-06947386 in Japanese adult patients with complicated intra-abdominal infection requiring hospitalization. This is a multicenter, open-label, single-arm study. All eligible participants will receive intravenous infusion of PF-06947386 followed by intravenous infusion of metronidazole.

Study Overview

• Status: Completed
• Conditions: Complicated Intra-abdominal Infection
• Intervention / Treatment: Drug: PF-06947386; Drug: Metronidazole

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260-8606
    • National Hospital Organization Chiba Medical Center
  • Fukuoka, Japan, 811-0213
    • Fukuoka Wajiro Hospital
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Kyoto, Japan, 612-8555
    • National Hospital Organization Kyoto Medical Center
  • Okayama, Japan, 700-8557
    • Okayama City General Medical Center Okayama City Hospital
  • Osaka, Japan, 530-0012
    • Osaka Saiseikai Nakatsu Hospital
  • Toyama, Japan, 930-0194
    • Toyama University Hospital
  • Yamagata, Japan, 990-8533
    • Yamagata City Hospital Saiseikan
  • Aichi
    • Nagoya, Aichi, Japan, 454-8502
      • Nagoya Ekisaikai Hospital
    • Nagoya, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center
    • Toyohashi, Aichi, Japan, 440-8510
      • National Hospital Organization Toyohashi Medical Center
  • Fukuoka
    • Kasuga, Fukuoka, Japan, 816-0864
      • Fukuoka Tokushukai Hospital
    • Kurume, Fukuoka, Japan, 830-8543
      • St.Mary's Hospital
  • Gunma
    • Maebashi, Gunma, Japan, 371-0821
      • Saiseikai Maebashi Hospital
    • Maebashi, Gunma, Japan, 371-0821
      • Gunma Saiseikai Maebashi Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 006-8555
      • Teine Keijinkai Hospital
  • Ibaraki
    • Tsuchiura, Ibaraki, Japan, 300-0028
      • Tsuchiura Kyodo General Hospital
    • Tsuchiura-shi, Ibaraki, Japan, 300-0028
      • Tsuchiura Kyodo General Hospital
  • Ishikawa
    • Kanazawa, Ishikawa, Japan, 920-8650
      • National Hospital Organization Kanazawa Medical Center
  • Kanagawa
    • Kawasaki-shi, Kanagawa, Japan, 212-0014
      • Kawasaki Saiwai Hospital
    • Sagamihara, Kanagawa, Japan, 252-5188
      • Sagamihara Kyodo Hospital
    • Yokohama, Kanagawa, Japan, 245-8575
      • National Hospital Organization Yokohama Medical Center
  • Nagano
    • Suwa, Nagano, Japan, 392-8510
      • Suwa Red Cross Hospital
  • Nagasaki
    • Omura, Nagasaki, Japan, 856-8562
      • National Hospital Organization Nagasaki Medical Center
  • Niigata
    • Nagaoka, Niigata, Japan, 940-8653
      • Nagaoka Chuo General Hospital
  • Okinawa
    • Naha, Okinawa, Japan, 902-8511
      • Naha City Hospital
  • Osaka
    • Izumisano, Osaka, Japan, 598-8577
      • Rinku General Medical Center
    • Kawachinagano, Osaka, Japan, 586-8521
      • National Hospital Organization Osaka Minami Medical Center
  • Yamanashi
    • Kofu, Yamanashi, Japan, 400-8506
      • Yamanashi Prefectural Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant who is capable of giving signed, dated and timed informed consent (or by their legally acceptable representative)
• Participant aged 20 years or older
• Participant who is willing and able to comply with all scheduled visits, treatment plan, laboratory tests, and other study procedures
• Confirmation of infection by surgical intervention within 24 hours of entry: evidence of systemic inflammatory response; physical findings consistent with intra-abdominal infection; supportive radiologic imaging findings of intra-abdominal infections
• Intraoperative/postoperative enrollment with visual confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis

Exclusion Criteria:

• Participant will undergo surgery for traumatic bowel perforation within 12 hours or perforation of gastroduodenal ulcers within 24 hours. Other intra-abdominal processes that are not infectious.
• Participant has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation
• Participant whose surgery will include staged abdominal repair, or "open abdomen" technique, or marsupialization.
• Participant has evidence of sepsis with shock not responding to IV fluid challenge or anticipated to require the administration of vasopressors for >24 hours
• Participant has suspected intra-abdominal infections due to fungus, parasites (eg, amebic liver abscess), virus, or tuberculosis
• Participant is considered unlikely to survive the 6- to 8-week study period or has a rapidly progressive or terminal illness
• Participant is pregnant or breastfeeding.
• Participant has received systemic antibacterial agents within the 72-hour period prior to study entry except for cases specified in the protocol such that participant is considered to have failed the previous treatment regimen, or participant has received systemic antibiotic agents no more than 24 hours (no more than one daily dose) within the 72-hour period prior to study entry, etc.
• Estimated CrCL ≤50 mL/min calculated by Cockcroft-Gault method.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-06947386 + Metronidazole; Multiple intravenous infusion of ceftazidime-avibactam followed by intravenous infusion of metronidazole, repeated every 8 hours for 5-14 days.	Drug: PF-06947386; Ceftazidime-Avibactam powder for concentrate for solution for infusion 2.0 g/ 0.5 g. Dosage will be adjusted based on renal function after enrollment.; Drug: Metronidazole; Metronidazole 0.5 g solution for injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinical Response at Test of Cure (TOC) Visit: Clinically Evaluable (CE) Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	TOC: Any day from Day 28 to Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Clinical Response at End of Treatment (EOT) and Late Follow-up (LFU) Visits: CE Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion.	EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
Number of Participants With Clinical Response at EOT and LFU Visits: Modified Intent-to-Treat (MITT) Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion.	EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
Number of Participants With Clinical Response at EOT and LFU Visits: Microbiological Modified Intent-to-Treat (mMITT) Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion.	EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Clinical Response at EOT and LFU Visits: Microbiologically Evaluable (ME) Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion.	EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Clinical Response EOT and LFU Visits: Extended Microbiologically Evaluable (eME) Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion.	EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
Number of Participants With Microbiological Response EOT, TOC and LFU Visits: mMITT Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data are not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Microbiological Response EOT, TOC and LFU Visits: ME Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Microbiological Response EOT, TOC and LFU Visits: eME Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: mMITT Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. Response of baseline pathogens cultured from intra-abdominal site or blood. A participant can have more than 1 pathogen. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: ME Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data are not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. Response of baseline pathogens cultured from intra-abdominal site or blood. A participant can have more than 1 pathogen. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: eME Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. Response of baseline pathogens cultured from intra-abdominal site or blood. A participant can have more than 1 pathogen. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Favorable Per-Pathogen Microbiological Response by Minimum Inhibitory Concentration (MIC) Categories at EOT, TOC and LFU Visits: mMITT Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Favorable Per-Pathogen Microbiological Response by MIC Categories at EOT, TOC and LFU Visits: ME Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Favorable Per-Pathogen Microbiological Response by MIC Categories at EOT, TOC and LFU Visits: eME Analysis Set	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. "Indeterminate" were not included in the denominator. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was defined as any untoward medical occurrence that, at any dose that resulted in death, was life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, a congenital anomaly/birth defect as per medical or scientific judgment. AEs included both SAEs and non-SAEs. TEAE was defined as an AE that emerges or worsened during the effective duration of treatment. All events that started on or after the first dosing day were flagged as TEAEs.	Up to Day 49
All-cause Mortality	Number of participants with death is presented.	Up to Day 49
Number of Participants Who Discontinued Treatment and Study Due to Adverse Events	Number of participants who discontinued treatment and study due to adverse events is presented.	Up to Day 49
Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	A semiautomated recording device was used to measure SBP and DBP with participant in a supine position after at least 5 minutes of rest.	Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Pulse Rate	Pulse rate was measured for in a supine position preceded by at least 5 minutes of rest for the participant.	Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Weight	Body weight was measured using a balance scale.	Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Temperature	Temperature was measured in a supine position, after the participant had rest for at least 5 minutes.	Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Respiratory Rate	Respiratory rate was measured in a supine position, after the participant had rest for at least 5 minutes.	Baseline, Day 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, and EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Laboratory Test Abnormalities	Criteria for abnormal laboratory values for chemistry parameters: Bilirubin >1.5*upper limit of normal (ULN), direct Bilirubin >1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase >3.0*ULN, total protein and albumin <0.8*lower limit of normal (LLN), urea nitrogen and creatinine >1.3*ULN, sodium >0.95*LLN, potassium >0.9*LLN and >1.1*ULN, calcium >0.9*LLN, glucose > 1.5*LLN; hematology parameters: Hemoglobin, hematocrit, erythrocytes <0.8*LLN, platelets <0.5*LLN and > 1.75*ULN, leukocytes <0.6*LLN and <0.6*LLN, lymphocytes <0.8* LLN, lymphocytes/leukocytes <0.8* LLN and >1.2*ULN, neutrophils >1.2*ULN, neutrophils/leukocytes <0.8*LLN and >1.2* ULN, basophils/leukocytes >1.2*ULN, eosinophils >1.2*ULN, eosinophils/leukocytes >1.2*ULN, monocytes and monocytes/leukocytes >1.2*ULN; Criteria for abnormal laboratory values for urinalysis parameters: urine glucose, >=1, urine protein >=1, urine Hemoglobin>=1.	Up to Day 49
Plasma Concentration of Avibactam	Plasma concentrations of avibactam was measured by nominal sampling window.	Day 3, Day 4, and Combination of Day 3 and 4: 15 minutes before or after infusion, 30-90 minutes after infusion, 300-360 minutes after infusion
Plasma Concentration of Ceftazidime	Plasma concentrations of ceftazidime was measured by nominal sampling window.	Day 3, Day 4, and Combination of Day 3 and 4: 15 minutes before or after infusion, 30-90 minutes after infusion, 300-360 minutes after infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinical Response at TOC Visit: MITT Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	TOC: Any day from Day 28 to Day 35
Number of Participants With Clinical Response at TOC Visit: mMITT Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	TOC: Any day from Day 28 to Day 35
Number of Participants With Clinical Response at TOC: ME Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	TOC: Any day from Day 28 to Day 35
Number of Participants With Clinical Response at TOC: eME Analysis Set	Clinical response: Clinical response of cure was defined as complete resolution or significant improvement of signs and symptoms of the index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within the abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptoms of intra-abdominal infection; Indeterminate: Study data was not available for evaluation of efficacy for any reason. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	TOC: Any day from Day 28 to Day 35
Number of Participants With Clinical Response at EOT, TOC and LFU Visits: Sepsis Participants Subset	Clinical response of cure was defined as complete resolution or significant improvement of signs & symptoms of index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from day of 1st IV infusion, allowed visit window was 28¬-35 calendar days after day of 1st IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptom of intra-abdominal infection; Indeterminate:Study data was not available for evaluation of efficacy for any reason. EOT: within 24 hours after completion of last IV infusion. LFU:after 42 calendar days from day of 1st IV infusion, allowed visit window was 42-49 calendar days from 1st IV infusion. TOC:after 28 calendar days from 1st IV infusion, allowed visit window was 28-35 calendar days after 1st IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Clinical Response at EOT, TOC and LFU Visits: Sepsis Evaluable Participants Subset	Clinical response of cure was defined as complete resolution or significant improvement of signs & symptoms of index infection such that no further antimicrobial therapy, drainage, or surgical intervention was necessary. TOC was after 28 calendar days from day of 1st IV infusion, allowed visit window was 28¬-35 calendar days after day of 1st IV infusion; clinical failure: Death related to intra-abdominal infection, Persisting or recurrent infection within abdomen, Postsurgical wound infections, participant who received treatment with additional antibiotics for ongoing symptom of intra-abdominal infection; Indeterminate:Study data was not available for evaluation of efficacy for any reason. EOT: within 24 hours after completion of last IV infusion. LFU:after 42 calendar days from day of 1st IV infusion, allowed visit window was 42-49 calendar days from 1st IV infusion. TOC:after 28 calendar days from 1st IV infusion, allowed visit window was 28-35 calendar days after 1st IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Microbiological Response EOT, TOC and LFU Visits: Sepsis Participants Subset	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data are not available for evaluation of efficacy. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Microbiological Response EOT, TOC and LFU Visits: Sepsis Evaluable Participants Subset	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data are not available for evaluation of efficacy. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: Sepsis Participants Subset	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. EOT: within 24 hours after completion of last IV infusion. Response of baseline pathogens cultured from intra-abdominal site or blood. A participant can have more than 1 pathogen. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: Sepsis Evaluation Participants Subset	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. EOT: within 24 hours after completion of last IV infusion. Response of baseline pathogens cultured from intra-abdominal site or blood. A participant can have more than 1 pathogen. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Favorable Per-Pathogen Microbiological Response by MIC Categories at EOT, TOC and LFU Visits: Sepsis Participants Subset	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Favorable Per-Pathogen Microbiological Response by MIC Categories at EOT, TOC and LFU Visits: Sepsis Evaluation Participants Subset	Microbiological response: Favorable microbiological response assessments include "eradication", "presumed eradication" and "colonization". Unfavorable microbiological response assessments include "persistence", "persistence with increasing MIC", and "presumed persistence. Indeterminate: Study data was not available for evaluation of efficacy. EOT: within 24 hours after completion of last IV infusion. LFU: after 42 calendar days from the day of the first IV infusion, the allowed visit window was 42 to 49 calendar days from the day of the first IV infusion. TOC: after 28 calendar days from the day of the first IV infusion, allowed visit window was 28 to 35 calendar days after the day of the first IV infusion.	EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
Number of Participants With Treatment Emergent AEs and SAEs: Sepsis Participants Subset	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was defined as any untoward medical occurrence that, at any dose that resulted in death, was life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, a congenital anomaly/birth defect as per medical or scientific judgment. AEs included both SAEs and non-SAEs. TEAE was defined as an AE that emerges or worsened during the effective duration of treatment. All events that started on or after the first dosing day were flagged as TEAEs.	Up to Day 49
Number of Participants With Treatment Emergent AEs and SAEs: Sepsis Evaluable Participants Subset	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was defined as any untoward medical occurrence that, at any dose that resulted in death, was life-threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent disability/incapacity, a congenital anomaly/birth defect as per medical or scientific judgment. AEs included both SAEs and non-SAEs. TEAE was defined as an AE that emerges or worsened during the effective duration of treatment. All events that started on or after the first dosing day were flagged as TEAEs.	Up to Day 49

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Actual): September 15, 2022
• Study Completion (Actual): September 15, 2022

Study Registration Dates

• First Submitted: June 4, 2021
• First Submitted That Met QC Criteria: June 14, 2021
• First Posted (Actual): June 15, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Ceftazidime-avibactam,; Metronidazole,; complicated intra-abdominal infection
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Intraabdominal Infections; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Metronidazole
• Other Study ID Numbers: C3591036

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes