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

Pfizer60 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Complicated Intra-abdominal Infection

Interventions

PF-06947386DRUG

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.

MetronidazoleDRUG

Metronidazole 0.5 g solution for injection.

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

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.

Locations (29)

Outcomes

Primary Outcomes

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.

Time frame: TOC: Any day from Day 28 to Day 35

Secondary Outcomes

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.

Time frame: EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49

Data from ClinicalTrials.gov

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Nagoya Ekisaikai Hospital

Nagoya, Aichi-ken, Japan

National Hospital Organization Nagoya Medical Center

Nagoya, Aichi-ken, Japan

National Hospital Organization Toyohashi Medical Center

Toyohashi, Aichi-ken, Japan

Fukuoka Tokushukai Hospital

Kasuga, Fukuoka, Japan

St.Mary's Hospital

Kurume, Fukuoka, Japan

Gunma Saiseikai Maebashi Hospital

Maebashi, Gunma, Japan

Saiseikai Maebashi Hospital

Maebashi, Gunma, Japan

Teine Keijinkai Hospital

Sapporo, Hokkaido, Japan

Tsuchiura Kyodo General Hospital

Tsuchiura, Ibaraki, Japan

Tsuchiura Kyodo General Hospital

Tsuchiura-shi, Ibaraki, Japan

...and 19 more locations

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.