A Phase 3 Study Of Intravenous Metronidazole For Intrabdominal Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the clinical efficacy and safety in Japanese adult subjects with Intra-abdominal/Pelvic infections receiving Metronidazole IV 1,500-2,000 mg/day in combination with ceftriaxone sodium.

Official Title
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A Phase 3, Multicenter, Unblind, Non-Comparative Study To Confirm Efficacy And Safety Of Intravenous Metronidazole In Patients With Intrabdominal Infection In Combination With Intravenous Ceftriaxone

Conditions
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Intra-abdominal Infections

Intervention / Treatment
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* Drug: Metronidazole
* Drug: Ceftriaxone sodium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 16 years of age or older. Diagnosed with intra-abdominal infections or pelvic inflammatory diseases. Can be obtained a specimen for bacteriological efficacy assessment. Exclusion Criteria: Known or suspected hypersensitivity, intolerance or contraindication to Metronidazole, Ceftriaxone sodium, or other cephem antibiotics. Severe renal dysfunction (creatinine clearance < 30 mL/min.) Reference: Cockcroft-Gault calculation formula. Hepatic dysfunction (AST, ALT, total bilirubin > 3 times upper limit of normal range values). Severe underlying disease; patients in which drug clinical evaluation is difficult because of confounding diseases.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metronidazole<br>Metronidazole will be administered at a dose of 500 mg TID (or QID for refractory or severe infection) in combination with ceftriaxone sodium | Drug: Metronidazole<br>* Metronidazole will be administered at a dose of 500 mg TID (or QID for refractory or severe infection) for 3 to 14 days, in principle. Treatment duration can be prolonged up to 21 days based on subject's condition.<br>Drug: Ceftriaxone sodium<br>* Ceftriaxone sodium will be administered at a daily dose of 2 g (strength) when metronidazole is administered TID or at a daily dose of 4 g (strength) when metronidazole is administered QID.<br>* Other names: ROCEPHIN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response: Response Rate (Data Review Committee Assessment) | Clinical response was evaluated by the data review committee as effective (cured or improved), ineffective (not meeting effective criteria), or indeterminate at the end of treatment (EOT) and the test of cure (TOC: 7 days after EOT) based on clinical symptoms, ultrasound images and necessity of other treatment. TOC was the primary analysis of this outcome measure. Cured = clinical symptoms and abnormal findings at the start of the study were disappeared and considered other antibiotics were not required during the study and after the assessment time point. Improved = clinical symptoms and abnormal findings at the start of the study were improved and considered other antibiotics were not required during the study and after the assessment time point. Response rate was calculated from the following formula; number of participants evaluated as effective over total number of participants that excluding ones evaluated as indeterminate multiplied by 100. | Baseline to EOT (up to 14 days), TOC | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response: Response Rate (Investigator Assessment) | Clinical response was evaluated by the investigator as effective (cured or improved), ineffective (not meeting effective criteria), or indeterminate at the end of treatment (EOT) and the test of cure (TOC: 7 days after EOT) based on clinical symptoms, ultrasound images and necessity of other treatment. TOC was the primary analysis of this outcome measure. Cured = clinical symptoms and abnormal findings at the start of the study were disappeared and considered other antibiotics were not required during the study and after the assessment time point. Improved = clinical symptoms and abnormal findings at the start of the study were improved and considered other antibiotics were not required during the study and after the assessment time point. Response rate was calculated from the following formula; number of participants evaluated as effective over total number of participants that excluding ones evaluated as indeterminate multiplied by 100. | Baseline to EOT (up to 14 days), TOC | 
| Percentage of Participants Who Was Assessed as Appropriate to Continue Treatment (Investigator Assessment) | The appropriateness of treatment continuation was evaluated on Day 4 by the investigator as continuation, discontinuation or indeterminate based on the clinical response. The percentage of participants was calculated from the following formula; number of participants assessed as continuation over total number of participants that excluding ones assessed as indeterminate multiplied by 100. | Baseline to Day 4 | 
| Bacteriological Response: Eradication Rate (Data Review Committee Assessment) | Bacteriological response was evaluated as eradication (eradication, presumed eradication or colonization), persistence, or indeterminate by the data review committee, at Day 4, at the end of treatment (EOT), and the test of cure (TOC: 7 days after EOT). Eradication Rate was calculated from the following formula, number of participants with bacteria eradication, presumed eradication or colonization over total number of participants that excluding ones evaluated as indeterminate multiplied by 100. | Baseline to Day 4, EOT (up to 14 days), TOC | 
| Bacteriological Response: Eradication Rate (Investigator Assessment) | Bacteriological response was evaluated as eradication (eradication, presumed eradication or colonization), persistence, or indeterminate by the investigator at the end of treatment (EOT), and the test of cure (TOC: 7 days after EOT). Eradication Rate was calculated from the following formula, number of participants with bacteria eradication, presumed eradication or colonization over total number of participants that excluding ones evaluated as indeterminate multiplied by 100. | Baseline to Day 4, EOT (up to 14 days), TOC | 
| Number of Participants Analyzed for Population Pharmacokinetics (PK) of Metronidazole | Population pharmacokinetic analysis of Metronidazole is conducted by combining current study data with other Metronidazole studies. | Four samples were taken at any infusion after the first dosing: during infusion, immediately after end of infusion, between 15 and 60 minutes after end of infusion, and between 2 hours and immediately before the start of the next infusion. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metronidazole, intra-abdominal infection, pelvic inflammatory disease, anaerobe