E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complicated Intra-Abdominal Infection (cIAI) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056570 |
E.1.2 | Term | Intra-abdominal infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the noninferiority of ceftazidime avibactam (CAZ-AVI) plus metronidazole compared to meropenem alone with respect to clinical cure at the test-of-cure in patients who have at least 1 identified pathogen. |
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E.2.2 | Secondary objectives of the trial |
To determine the efficacy of CAZ-AVI plus metronidazole compared to meropenem with respect to the clinical cure at the end of treatment with IV therapy (EOT) and at the late follow-up (LFU)
To determine the per-patient and per-pathogen microbiologic response of CAZ-AVI plus metronidazole compared to meropenem at EOT, TOC, and LFU
To evaluate the efficacy of CAZ-AVI plus metronidazole versus meropenem in
pathogens resistant to ceftazidime
To compare the time to first defervescence of CAZ-AVI plus metronidazole versus
meropenem
To evaluate the safety and tolerability profile of CAZ-AVI plus metronidazole
compared to meropenem
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient must be 18 to 90 years of age inclusive.
2. Female patient is authorized to participate if at least one of the following criteria are met:
(a) Surgical sterilization
(b) Age ≥50 years and postmenopausal as defined by amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments
(c) Age <50 years and postmenopausal as defined by documented LH and FSH levels in the postmenopausal range PLUS amenorrhea for 12 months or more following cessation of all exogenous hormonal treatments
(d) Patient has a negative serum pregnancy test (serum ß-human chorionic gonadotropin [ßhCG]) within 1 day prior to study entry, and agrees to use highly effective contraception methods during treatment and for at least 7 days after last dose of IV study therapy.
3. Intraoperative/postoperative enrollment with confirmation (presence of pus within the abdominal cavity) of an intra-abdominal infection associated with peritonitis.
4. 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. |
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E.4 | Principal exclusion criteria |
1. Patient is diagnosed with traumatic bowel perforation undergoing surgery within 12 hours; perforation of gastroduodenal ulcers undergoing surgery within 24 hours. Other intra-abdominal processes in which primary etiology is not likely to be infectious.
2. Patient has abdominal wall abscess or bowel obstruction without perforation or ischemic bowel without perforation.
3. Patient has suspected intra-abdominal infections due to fungus, parasites, virus or tuberculosis.
4. Patient is considered unlikely to survive the 6 to 8 week study period or has a rapidly progressive or terminal illness, including septic shock that is associated with a high risk of mortality. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To assess the proportion of patients with clinical cure in the microbiological modified intent-to-treat analysis set. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the test of cure visit |
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E.5.2 | Secondary end point(s) |
1. To assess the proportion of patients with clinical cure in the
microbiologically evaluable and extended microbiologically evaluable
analysis sets.
2. To assess the proportion of patients with clinical cure in the
microbiological modified intent-to-treat, microbiologically evaluable, and
extended microbiologically evaluable analysis sets.
3. To assess the proportion of patients with clinical cure in the clinically
evaluable anlaysis set.
4. To assess the proportion of patients with a favorable per-patient
microbiological response in the microbiological modified intent to treat,
microbiologically evaluable, and extended microbiologically evaluable
analysis sets.
5. To assess the proportion of favorable per-pathogen microbiological
response in the microbiological modified intent to treat,
microbiologically evaluable, and extended microbiologically evaluable
anlaysis sets.
6. To assess the favorable per-pathogen microbiologic response by
minimum inhibitory concentration (MIC) categories in the
microbiological modified intent to treat, microbiologically evaluable, and
extended microbiologically evaluable analysis sets.
7. To assess the favorable per-patient clinical response and favorable per
patient microbiological response for patients infected with ceftazidimeresistant
pathogens in the microbiological modified intent to treat,
microbiologically evaluable, and extended microbiologically evaluable
analysis sets.
8. To assess the proportion of patients with a favorable per pathogen
microbiological response for patients infected with ceftazidime-resistant
pathogens in the microbiological modified intent to treat,
microbiologically evaluable, and extended microbiologically evaluable
anlaysis sets.
9. To assess the time to first defervescence in the clinically evaluable,
microbiologically evaluable, and extended microbiologically evaluable
anlaysis sets for patients who have fever at study entry.
10. To assess the safety and tolerability by incidence and severity of
adverse events and serious adverse events, vital signs, clinical
laboratory tests, ECGs and physical exams.
11. Pharmacokinetics: maximum concentration (Cmax), minimum
concentration, area under the plasma concentration time curve at steady
state, and terminal half-life |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. at the test of cure visit
2. at the end of treatment and late follow-up visits
3. at the end of treatment, test of cure and late follow-up visits
4. at the end of treatment, test of cure and late follow-up visits
5. at the end of treatment, test of cure and late follow-up visits
6. at the end of treatment, test of cure and late follow-up visits
7. at the test of cure visit
8. at the test of cure visit
9. while on IV study therapy
10. study duration
11. Anytime within 15 minutes prior to or after stopping study drug,
anytime between 30 and 90 minutes after stopping study drug, anytime
between 300 minutes and 360 minutes after stopping study drug |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Brazil |
Bulgaria |
Canada |
Czech Republic |
Hungary |
India |
Israel |
Italy |
Lithuania |
Mexico |
Peru |
Portugal |
Romania |
Russian Federation |
Serbia |
South Africa |
Spain |
Taiwan |
Thailand |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |