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

• Sponsor: Pfizer (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04927312
• Collaborator: (none)
• Enrollment: 60
• Locations: 34
• Arm: 1
• Anticipated Duration (Months): 12.6
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Complicated Intra-abdominal Infection	Drug: PF-06947386; Drug: Metronidazole	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 1, 2021
• Anticipated Primary Completion Date: Oct 19, 2022
• Anticipated Study Completion Date: Oct 19, 2022

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. The percentage of participants in clinically evaluable (CE) analysis set having clinical cure [Test of Cure (TOC) on study Day 28-35]

   The percentage of participants in CE analysis set having clinical cure will be calculated as the primary estimand of the primary endpoint. As an efficacy evaluation criterion, it will be confirmed that the point estimate of proportion of patients with clinical cure at TOC visit in the CE analysis set (the primary analysis) is ≥78%.

2. The percentage of participants in modified intent-to-treat (MITT) analysis set having clinical cure [TOC on study Day 28-35]

   The percentage of participants in MITT analysis set having clinical cure will be calculated as the supportive estimand of the primary endpoint.

3. The percentage of participants in microbiological modified intent-to-treat (mMITT) analysis set having clinical cure [TOC on study Day 28-35]

   The percentage of participants in mMITT analysis set having clinical cure will be calculated as the supportive estimand of the primary endpoint.

4. The percentage of participants in microbiologically evaluable (ME) analysis set having clinical cure [TOC on study Day 28-35]

   The percentage of participants in ME analysis set having clinical cure will be calculated as the supportive estimand of the primary endpoint.

5. The percentage of participants in extended microbiologically evaluable (eME) analysis set having clinical cure [TOC on study Day 28-35]

   The percentage of participants eME analysis set having clinical cure will be calculated as the supportive estimand of the primary endpoint

Secondary Outcome Measures

1. The percentage of participants in CE analysis set having clinical cure [End of Treatment (EOT, within 24 hours after completion of last IV infusion) and LFU (Late Follow-Up) on study Day 42-49]

   The percentage of participants in CE analysis set having clinical cure will be calculated.

2. The percentage of participants in MITT analysis set having clinical cure [EOT (within 24 hours after completion of last IV infusion) and LFU on study Day 42-49]

   The percentage of participants in MITT analysis set having clinical cure will be calculated.

3. The percentage of participants in mMITT analysis set having clinical cure [EOT (within 24 hours after completion of last IV infusion) and LFU on study Day 42-49]

   The percentage of participants in mMITT analysis set having clinical cure will be calculated.

4. The percentage of participants in ME analysis set having clinical cure [EOT (within 24 hours after completion of last IV infusion) and LFU on study Day 42-49]

   The percentage of participants in ME analysis set having clinical cure will be calculated.

5. The percentage of participants in eME analysis set having clinical cure [EOT (within 24 hours after completion of last IV infusion) and LFU on study Day 42-49]

   The percentage of participants in eME analysis set having clinical cure will be calculated.

6. The percentage of participants in mMITT analysis set having favorable microbiological response per-patient [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

   The percentage of participants in mMITT analysis set having favorable microbiological response per-patient will be calculated. Participants with "Indeterminate" are not included in the denominator.

7. The percentage of participants in ME analysis set having favorable microbiological response per-patient [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

   The percentage of participants in ME analysis set having favorable microbiological response per-patient will be calculated. Participants with "Indeterminate" are not included in the denominator.

8. The percentage of participants in eME analysis set having favorable microbiological response per-patient [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

   The percentage of participants in eME analysis set having favorable microbiological response per-patient will be calculated. Participants with "Indeterminate" are not included in the denominator.

9. The percentage of participants in mMITT analysis set having favorable microbiological response per-pathogen [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

   The percentage of participants in mMITT analysis set having favorable microbiological response per-pathogen will be calculated. Participants with "Indeterminate" are not included in the denominator.

10. The percentage of participants in ME analysis set having favorable microbiological response per-pathogen [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in ME analysis set having favorable microbiological response per-pathogen will be calculated. Participants with "Indeterminate" are not included in the denominator.

11. The percentage of participants in eME analysis set having favorable microbiological response per-pathogen [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in eME analysis set having favorable microbiological response per-pathogen will be calculated. Participants with "Indeterminate" are not included in the denominator.

12. The percentage of participants in mMITT analysis set having favorable microbiological response per-pathogen by MIC categories [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in mMITT analysis set having favorable microbiological response per-pathogen by MIC categories will be calculated. Participants with "Indeterminate" are not included in the denominator.

13. The percentage of participants in ME analysis set having favorable microbiological response per-pathogen by MIC categories [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in ME analysis set having favorable microbiological response per-pathogen by MIC categories will be calculated. Participants with "Indeterminate" are not included in the denominator.

14. The percentage of participants in eME analysis set having favorable microbiological response per-pathogen by MIC categories [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in eME analysis set having favorable microbiological response per-pathogen by MIC categories will be calculated. Participants with "Indeterminate" are not included in the denominator.

15. Percentage of participants experiencing Adverse Events [Up to a minimum of approximately 28 days after the last administration of the study drug]

    Safety and tolerability profile of PF-06947386 plus metronidazole in the treatment of patients with cIAIs will be evaluated.

16. Percentage of participants experiencing Serious Adverse Events [Up to a minimum of approximately 28 days after the last administration of the study drug]

    Safety and tolerability profile of PF-06947386 plus metronidazole in the treatment of patients with cIAIs will be evaluated.

17. Ceftazidime plasma concentrations by nominal sampling window [Day 3, Day 4]

    Pharmacokinetics of ceftazidime in patients with cIAIs will be evaluated.

18. Avibactam plasma concentrations by nominal sampling window [Day 3, Day 4]

    Pharmacokinetics of avibactam in patients with cIAIs will be evaluated.

19. The percentage of participants in the sepsis population having clinical cure [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in the sepsis population having clinical cure will be calculated.

20. The percentage of participants in the sepsis population having favorable microbiological response per-patient [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in the sepsis population having favorable microbiological response per-patient will be calculated. Participants with "Indeterminate" are not included in the denominator.

21. The percentage of participants in the sepsis population having favorable microbiological response per-pathogen [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in the sepsis population having favorable microbiological response per-pathogen will be calculated. Participants with "Indeterminate" are not included in the denominator.

22. The percentage of participants in the sepsis population having favorable microbiological response per-pathogen by MIC categories [EOT (within 24 hours after completion of last IV infusion), TOC on study Day 28-35, and LFU on study Day 42-49]

    The percentage of participants in the sepsis population having favorable microbiological response per-pathogen by MIC categories will be calculated. Participants with "Indeterminate" are not included in the denominator.

23. Percentage of participants experiencing Adverse Events in the sepsis population [Up to a minimum of approximately 28 days after the last administration of the study drug]

    Safety and tolerability profile of PF-06947386 plus metronidazole in the sepsis population will be evaluated.

24. Percentage of participants experiencing Serious Adverse Events in the sepsis population [Up to a minimum of approximately 28 days after the last administration of the study drug]

    Safety and tolerability profile of PF-06947386 plus metronidazole in the sepsis population will be evaluated.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nagoya Ekisaikai Hospital	Nagoya	Aichi	Japan	454-8502
2	National Hospital Organization Nagoya Medical Center	Nagoya	Aichi	Japan	460-0001
3	National Hospital Organization Toyohashi Medical Center	Toyohashi	Aichi	Japan	440-8510
4	Fukuoka Tokushukai Hospital	Kasuga	Fukuoka	Japan	816-0864
5	St.Mary's Hospital	Kurume	Fukuoka	Japan	830-8543
6	Fukuoka Shinmizumaki Hospital	Onga-gun	Fukuoka	Japan	807-0051
7	Saiseikai Maebashi Hospital	Maebashi	Gunma	Japan	371-0821
8	National Hospital Organization Fukuyama Medical Center	Fukuyama	Hiroshima	Japan	720-8520
9	Teine Keijinkai Hospital	Sapporo	Hokkaido	Japan	006-8555
10	KKR Sapporo Medical Center	Sapporo	Hokkaido	Japan	062-0931
11	Tsuchiura Kyodo General Hospital	Tsuchiura	Ibaraki	Japan	300-0028
12	Ishikawa Prefectural Central Hospital	Kanazawa	Ishikawa	Japan	920-8530
13	National Hospital Organization Kanazawa Medical Center	Kanazawa	Ishikawa	Japan	920-8650
14	Kawasaki Saiwai Hospital	Kawasaki-shi	Kanagawa	Japan	212-0014
15	Sagamihara Kyodo Hospital	Sagamihara	Kanagawa	Japan	252-5188
16	National Hospital Organization Yokohama Medical Center	Yokohama	Kanagawa	Japan	245-8575
17	Tohoku University Hospital	Sendai	Miyagi	Japan	980-8574
18	Suwa Red Cross Hospital	Suwa	Nagano	Japan	392-8510
19	National Hospital Organization Nagasaki Medical Center	Omura	Nagasaki	Japan	856-8562
20	Nagaoka Chuo General Hospital	Nagaoka	Niigata	Japan	940-8653
21	Naha City Hospital	Naha	Okinawa	Japan	902-8511
22	Rinku General Medical Center	Izumisano	Osaka	Japan	598-8577
23	National Hospital Organization Osaka Minami Medical Center	Kawachinagano	Osaka	Japan	586-8521
24	National Hospital Organization Higashi Ohmi General Medical Center	Higashiomi	Shiga	Japan	527-8505
25	Yamanashi Prefectural Central Hospital	Kofu	Yamanashi	Japan	400-8506
26	National Hospital Organization Chiba Medical Center	Chiba		Japan	260-8606
27	Fukui-Ken Saiseikai Hospital	Fukui		Japan	918-8503
28	Fukuoka Wajiro Hospital	Fukuoka		Japan	811-0213
29	National Hospital Organization Kumamoto Medical Center	Kumamoto		Japan	860-0008
30	National Hospital Organization Kyoto Medical Center	Kyoto		Japan	612-8555
31	Okayama City General Medical Center Okayama City Hospital	Okayama		Japan	700-8557
32	Osaka Saiseikai Nakatsu Hospital	Osaka		Japan	530-0012
33	Toyama University Hospital	Toyama		Japan	930-0194
34	Yamagata City Hospital Saiseikan	Yamagata		Japan	990-8533

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04927312
• Other Study ID Numbers: C3591036
• First Posted: Jun 15, 2021
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pfizer: Ceftazidime-avibactam,; Metronidazole,; complicated intra-abdominal infection
• Additional relevant MeSH terms: Infections; Communicable Diseases; Intraabdominal Infections; Metronidazole

Study Results

No Results Posted as of Aug 4, 2022