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 (CAZ104) 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 CAZ104 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 CAZ104 plus metronidazole compared to meropenem at EOT, TOC, and LFU
To evaluate the efficacy of CAZ104 plus metronidazole versus meropenem in
pathogens resistant to ceftazidime
To compare the time to first defervescence of CAZ104 plus metronidazole versus
meropenem
To evaluate the safety and tolerability profile of CAZ104 plus metronidazole
compared to meropenem
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
18 to 90 years of age inclusive - 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. - Intraoperative/postoperative enrollment with confirmation
(presence of pus within the abdominal cavity) of an intra-abdominal
infection associated with peritonitis - Confirmation of infection by
surgical intervention within 24 hours of entry: evidence of systemic
inflammatory response; physical findings consistent with intraabdominal
infection; supportive radiologic imaging findings of intraabdominal
infections |
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E.4 | Principal exclusion criteria |
Patient is diagnosed with traumatic bowel perforation undergoing
surgery within 12 hours; perforation of gastroduodenal ulcers
undergoing surgery within 24 hours. Other intraabdominal processes in
which primary etiology is not likely to be infectious - Patient has
abdominal wall abscess or bowel obstruction without perforation or
ischemic bowel without perforation - Patient has suspected intraabdominal
infections due to fungus, parasites, virus or tuberculosis -
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 themicrobiologically evaluable and extended microbiologically evaluableanalysis sets.
2. To assess the proportion of patients with clinical cure in themicrobiological modified intent-to-treat, microbiologically evaluable, andextended microbiologically evaluable analysis sets.
3. To assess the proportion of patients with clinical cure in the clinicallyevaluable anlaysis set.
4. To assess the proportion of patients with a favorable per-patientmicrobiological response in the microbiological modified intent to treat,microbiologically evaluable, and extended microbiologically evaluableanalysis sets.
5. To assess the proportion of favorable per-pathogen microbiologicalresponse in the microbiological modified intent to treat,microbiologically evaluable, and extended microbiologically evaluableanlaysis sets.
6. To assess the favorable per-pathogen microbiologic response byminimum inhibitory concentration (MIC) categories in themicrobiological modified intent to treat, microbiologically evaluable, andextended microbiologically evaluable analysis sets.
7. To assess the favorable per-patient clinical response and favorable perpatient microbiological response for patients infected with ceftazidimeresistantpathogens in the microbiological modified intent to treat,microbiologically evaluable, and extended microbiologically evaluableanalysis sets.
8. To assess the proportion of patients with a favorable per pathogenmicrobiological response for patients infected with ceftazidime-resistantpathogens in the microbiological modified intent to treat,microbiologically evaluable, and extended microbiologically evaluableanlaysis sets.
9. To assess the time to first defervescence in the clinically evaluable,microbiologically evaluable, and extended microbiologically evaluableanlaysis sets for patients who have fever at study entry.
10. To assess the safety and tolerability by incidence and severity ofadverse events and serious adverse events, vital signs, clinicallaboratory tests, ECGs and physical exams.
11. Pharmacokinetics: maximum concentration (Cmax), minimumconcentration, area under the plasma concentration time curve at steadystate, 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, anytimebetween 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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
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 |
Belgium |
Brazil |
Bulgaria |
Canada |
Chile |
Czech Republic |
France |
Germany |
Greece |
India |
Israel |
Italy |
Romania |
Russian Federation |
Spain |
Thailand |
Turkey |
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 |