Clinical trial NCT04927312: Study to Assess Efficacy and Safety of PF-06947386 in Japanese Adult Patients With Complicated Intra-abdominal Infection
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Complicated Intra-abdominal Infection
Keywords: Ceftazidime-avibactam,
Metronidazole,
complicated intra-abdominal infection
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-06-15
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Clinical Response at Test of Cure (TOC) Visit: Clinically Evaluable (CE) Analysis Set
timeFrame: TOC: Any day from Day 28 to Day 35
Secondary outcomes:
measure: Percentage of Participants With Clinical Response at End of Treatment (EOT) and Late Follow-up (LFU) Visits: CE Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Clinical Response at EOT and LFU Visits: Modified Intent-to-Treat (MITT) Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Clinical Response at EOT and LFU Visits: Microbiological Modified Intent-to-Treat (mMITT) Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Clinical Response at EOT and LFU Visits: Microbiologically Evaluable (ME) Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Clinical Response EOT and LFU Visits: Extended Microbiologically Evaluable (eME) Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Microbiological Response EOT, TOC and LFU Visits: mMITT Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Microbiological Response EOT, TOC and LFU Visits: ME Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Microbiological Response EOT, TOC and LFU Visits: eME Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: mMITT Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: ME Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: eME Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response by Minimum Inhibitory Concentration (MIC) Categories at EOT, TOC and LFU Visits: mMITT Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response by MIC Categories at EOT, TOC and LFU Visits: ME Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response by MIC Categories at EOT, TOC and LFU Visits: eME Analysis Set
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: Up to Day 49
measure: All-cause Mortality
timeFrame: Up to Day 49
measure: Number of Participants Who Discontinued Treatment and Study Due to Adverse Events
timeFrame: Up to Day 49
measure: 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)
timeFrame: 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
measure: Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Pulse Rate
timeFrame: 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
measure: Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Weight
timeFrame: 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
measure: Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Temperature
timeFrame: 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
measure: Change From Baseline in Vital Sign Parameters at Day 2 to 14, EOT, TOC and, LFU Visits: Respiratory Rate
timeFrame: 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
measure: Number of Participants With Laboratory Test Abnormalities
timeFrame: Up to Day 49
measure: Plasma Concentration of Avibactam
timeFrame: 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
measure: Plasma Concentration of Ceftazidime
timeFrame: 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 outcomes:
measure: Number of Participants With Clinical Response at TOC Visit: MITT Analysis Set
timeFrame: TOC: Any day from Day 28 to Day 35
measure: Number of Participants With Clinical Response at TOC Visit: mMITT Analysis Set
timeFrame: TOC: Any day from Day 28 to Day 35
measure: Number of Participants With Clinical Response at TOC: ME Analysis Set
timeFrame: TOC: Any day from Day 28 to Day 35
measure: Number of Participants With Clinical Response at TOC: eME Analysis Set
timeFrame: TOC: Any day from Day 28 to Day 35
measure: Number of Participants With Clinical Response at EOT, TOC and LFU Visits: Sepsis Participants Subset
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Clinical Response at EOT, TOC and LFU Visits: Sepsis Evaluable Participants Subset
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Microbiological Response EOT, TOC and LFU Visits: Sepsis Participants Subset
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Microbiological Response EOT, TOC and LFU Visits: Sepsis Evaluable Participants Subset
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Percentage of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: Sepsis Participants Subset
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Favorable Per-Pathogen Microbiological Response at EOT, TOC and LFU Visits: Sepsis Evaluation Participants Subset
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Favorable Per-Pathogen Microbiological Response by MIC Categories at EOT, TOC and LFU Visits: Sepsis Participants Subset
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Favorable Per-Pathogen Microbiological Response by MIC Categories at EOT, TOC and LFU Visits: Sepsis Evaluation Participants Subset
timeFrame: EOT: 24 hours after last IV infusion; TOC: Any day from Day 28 to 35; LFU: Any day from Day 42 to Day 49
measure: Number of Participants With Treatment Emergent AEs and SAEs: Sepsis Participants Subset
timeFrame: Up to Day 49
measure: Number of Participants With Treatment Emergent AEs and SAEs: Sepsis Evaluable Participants Subset
timeFrame: Up to Day 49
Locations:
city: Nagoya
country: Japan
facility: Nagoya Ekisaikai Hospital
state: Aichi
city: Nagoya
country: Japan
facility: National Hospital Organization Nagoya Medical Center
state: Aichi
city: Toyohashi
country: Japan
facility: National Hospital Organization Toyohashi Medical Center
state: Aichi
city: Kasuga
country: Japan
facility: Fukuoka Tokushukai Hospital
state: Fukuoka
city: Kurume
country: Japan
facility: St.Mary's Hospital
state: Fukuoka
city: Maebashi
country: Japan
facility: Gunma Saiseikai Maebashi Hospital
state: Gunma
city: Maebashi
country: Japan
facility: Saiseikai Maebashi Hospital
state: Gunma
city: Sapporo
country: Japan
facility: Teine Keijinkai Hospital
state: Hokkaido
city: Tsuchiura-shi
country: Japan
facility: Tsuchiura Kyodo General Hospital
state: Ibaraki
city: Tsuchiura
country: Japan
facility: Tsuchiura Kyodo General Hospital
state: Ibaraki
city: Kanazawa
country: Japan
facility: National Hospital Organization Kanazawa Medical Center
state: Ishikawa
city: Kawasaki-shi
country: Japan
facility: Kawasaki Saiwai Hospital
state: Kanagawa
city: Sagamihara
country: Japan
facility: Sagamihara Kyodo Hospital
state: Kanagawa
city: Yokohama
country: Japan
facility: National Hospital Organization Yokohama Medical Center
state: Kanagawa
city: Suwa
country: Japan
facility: Suwa Red Cross Hospital
state: Nagano
city: Omura
country: Japan
facility: National Hospital Organization Nagasaki Medical Center
state: Nagasaki
city: Nagaoka
country: Japan
facility: Nagaoka Chuo General Hospital
state: Niigata
city: Naha
country: Japan
facility: Naha City Hospital
state: Okinawa
city: Izumisano
country: Japan
facility: Rinku General Medical Center
state: Osaka
city: Kawachinagano
country: Japan
facility: National Hospital Organization Osaka Minami Medical Center
state: Osaka
city: Kofu
country: Japan
facility: Yamanashi Prefectural Central Hospital
state: Yamanashi
city: Chiba
country: Japan
facility: National Hospital Organization Chiba Medical Center
city: Fukuoka
country: Japan
facility: Fukuoka Wajiro Hospital
city: Kumamoto
country: Japan
facility: National Hospital Organization Kumamoto Medical Center
city: Kyoto
country: Japan
facility: National Hospital Organization Kyoto Medical Center
city: Okayama
country: Japan
facility: Okayama City General Medical Center Okayama City Hospital
city: Osaka
country: Japan
facility: Osaka Saiseikai Nakatsu Hospital
city: Toyama
country: Japan
facility: Toyama University Hospital
city: Yamagata
country: Japan
facility: Yamagata City Hospital Saiseikan
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: