A Study Of Intravenous Sulopenem And Oral PF-03709270 In Community Acquired Pneumonia That Requires Hospitalization

Study Overview
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Brief Summary
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The purpose of this study is to test if intravenous sulopenem and an oral drug, PF-03709270 are safe and effective in patients that are hospitalized with community acquired pneumonia.

Official Title
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A Phase 2 Randomized, Double-blind, Double-dummy Efficacy, Safety And Tolerability Study Of Iv Sulopenem With Switch To Oral Pf-03709270 Compared To Ceftriaxone With Step Down To Amoxicillin/Clavulanate Potassium (Augmentin) In Subjects With Community Acquired Pneumonia (Cap) Requiring Hospitalization

Conditions
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Pneumonia, Bacterial

Intervention / Treatment
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* Drug: sulopenem and PF-03709270
* Drug: Sulopenem and PF-03709270
* Drug: Ceftriaxone and amoxicillin/clavulanate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized male or female patients 18 years of age or older. Female patients of childbearing potential must not be pregnant. Must exhibit at least two pre-specified clinical symptoms/signs of pneumonia. Must require hospitalization for the pneumonia. Chest Xray must be suggestive of a pneumonia. Exclusion Criteria: Hospital or ventilator associated pneumonia. Patients with cystic fibrosis, pneumocystis carinii pneumonia or active tuberculosis. Previous treatment for the current pneumonia episode received for more than 24 hours. Allergies to penems or beta lactams.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Loading dose of IV sulopenem with switch to oral PF-03709270 | Drug: sulopenem and PF-03709270<br>* Sulopenem - 600 mg infused over 1 hour, single loading dose and switch to oral PF-03709270 - 1000 mg twice a day<br>|
| Experimental: 2<br>IV sulopenem with switch to oral PF-03709270 | Drug: Sulopenem and PF-03709270<br>* Sulopenem - 600 mg infused over 1 hour twice daily for a minimum of 2 days and switch to oral PF-03709270 - 1000 mg twice a day<br>|
| Active Comparator: 3<br>IV ceftriaxone with switch to oral amoxicillin/clavulanate potassium comparator | Drug: Ceftriaxone and amoxicillin/clavulanate<br>* IV ceftriaxone (2g) infused over 30 minutes QD (once daily) for minimum of 2 days Step down oral amoxicillin/clavulanate potassium suspension (400 mg/5 ml) BID (every 12 hours)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response at Test of Cure (TOC) Visit | Clinical response (CR) was based primarily on global assessment of clinical presentation of participant made by investigator at evaluation time point. At TOC (7 to 14 days after end of treatment [EOT]) CR was evaluated as cure=resolution of clinical signs and symptoms related to the acute infection, or clinical improvement in which no additional antibiotics were deemed necessary when compared to baseline; failure=persistence or progression of baseline signs and symptoms of pneumonia (for example: body temperature, white blood cell [WBC] count, respiratory rate, auscultatory findings, cough, sputum production), development of new pulmonary or extrapulmonary clinical findings consistent with active infection and those participants that were not assessed for clinical response due to early discontinuation; indeterminate=extenuating circumstances precluded classification to 1 of the above. | 7 to 14 days after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit | CR was based primarily on global assessment of clinical presentation of participant made by investigator at evaluation time point. At EOT (Day 7 to 10) and follow-up (15 to 28 days after EOT), CR was evaluated as cure=resolution of clinical signs and symptoms related to the acute infection, or clinical improvement in which no additional antibiotics were deemed necessary when compared to baseline; failure=persistence or progression of baseline signs and symptoms of pneumonia, development of new pulmonary or extrapulmonary clinical findings consistent with active infection and those participants that were not assessed for clinical response due to early discontinuation; with additional CR evaluated as improvement= of few not all signs and symptoms of pneumonia when compared to baseline and no additional antibacterial treatment required at EOT and indeterminate=extenuating circumstances precluded classification to 1 of the above at follow-up. | EOT (Day 7 to 10) , Follow-up (15 to 28 days after EOT) | 
| Number of Participants With Microbiological Response at Test of Cure (TOC) Visit | Microbiological response assessed at participant level. Eradication=the absence of the original pathogens from the post-treatment TOC culture of specimen from the original site of infection. Presumed eradication=the complete resolution of signs and symptoms associated with cessation of culturable specimen (for example, sputum). Persistence=the presence of the original pathogen in the post-treatment TOC culture specimen from the original site of infection. Presumed persistence=in a participant who was judged to be a clinical failure and a culture of specimen was not possible or was not done, it was presumed that there was persistence of the pathogen. Not applicable microbiologic response included participants that did not have post-treatment microbiologic cultures due to early discontinuation. Data reported for eradication is combination of eradication and presumed eradication data and data reported for persistence is combination of persistence and presumed persistence data. | 7 to 14 days after EOT | 
| Change From Baseline in Community Acquired Pneumonia (CAP) Symptom Questionnaire at Test of Cure (TOC) and Follow-up Visit | The CAP Symptom Questionnaire was a participant reported questionnaire administered by interview. It consisted of 12 items (coughing, chest pains, shortness of breath, sweating, chills, headache, nausea, muscle pain, lack of appetite, trouble concentrating, trouble sleeping, and fatigue). Depending on if the participant had or not had symptoms/problems, they were asked how much they had been bothered by the symptoms/problems over the previous 24 hours. CAP items were rated on the 6-point response scale (0 = participant did not have symptom/problem: 1 = not at all, 2 = a little, 3 = moderately, 4 = quite a bit, 5 = extremely; if the participant had the symptom/problem and were bothered). All 12 items score were summed and averaged to produce a CAP symptom score (range, 0 to 6). High values indicated poorer outcomes (higher symptom bothersomeness). | Baseline, TOC (7 to 14 days after end of treatment), Follow-up (15 to 28 days after EOT) |