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

JRCT ID: jRCT2061210026

Registered date:21/07/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Complicated Intra-abdominal Infection
• Date of first enrollment: 01/10/2021
• Target sample size: 60
• Study type: Interventional

Intervention(s)

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.

Outcome(s)

Primary Outcome

Primary Outcomes:
The percentage of participants having clinical cure.
* Time Frame:
Test of Cure (TOC) on study Day 28-35.
* Analysis set:
Clinically Evaluable (CE) (Primary), Modified Intent-to-Treat (MITT), Microbiological Modified Intent-to-Treat (mMITT), Microbiologically Evaluable (ME), and extended-Microbiologically Evaluable (eME) analysis sets.

Secondary Outcome

Secondary Outcomes:
1. The percentage of participants having clinical cure.
* Time Frame: End of Treatment (EOT, within 24 hours after completion of last IV infusion) and LFU (Late Follow-Up) on study Day 42-49.
* Analysis set: CE, MITT, mMITT, ME, and eME analysis sets.

2. The percentage of participants having favorable per-patient microbiological response.
* Time Frame: EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49.
* Analysis set: mMITT, ME, and eME analysis sets.

3. The percentage of participants having favorable per-pathogen microbiological response.
* Time Frame: EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49.
* Analysis set: mMITT, ME, and eME analysis sets.

4. The percentage of participants having favorable per-pathogen microbiological response by MIC categories.
* Time Frame: EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49.
* Analysis set: mMITT, ME, and eME analysis sets.

5. Percentage of participants experiencing adverse events/serious adverse events.
* Time Frame: Up to a minimum of approximately 28 days after the last administration of study drug.
* Analysis set: Safety analysis set.

6. Ceftazidime/avibactam plasma concentrations by nominal sampling window.
* Time Frame: Day 3, Day 4.
* Analysis set: PK analysis set.

7. Percentage of sepsis patients having clinical cure.
* Time Frame: EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49.
* Analysis set: Sepsis patients subset, sepsis evaluable patients subset.

8. Percentage of sepsis patients having per-patient favorable microbiological response.
* Time Frame: EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49.
* Analysis set: Sepsis patients subset, sepsis evaluable patients subset.

9. Percentage of sepsis patients having favorable per-pathogen microbiological response.
* Time Frame: Time Frame: EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49.
* Analysis set: Sepsis patients subset, sepsis evaluable patients subset.

10. Percentage of sepsis patients having favorable per-pathogen microbiological response by MIC category.
* Time Frame: EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49.
* Analysis set: Sepsis patients subset, sepsis evaluable patients subset.

11. Percentage of participants experiencing adverse events/serious adverse events in sepsis patients.
* Time Frame: Up to a minimum of approximately 28 days after the last administration of the study drug.
* Analysis set: Sepsis patients subset, sepsis evaluable patients subset.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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

Exclude 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.

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT04927312