Trial Outcomes & Findings for A Study Of Intravenous Sulopenem And Oral PF-03709270 In Community Acquired Pneumonia That Requires Hospitalization (NCT NCT00797108)

Last Updated: 2016-03-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

7 to 14 days after end of treatment

Results posted on

2016-03-10

Participant Flow

Participant milestones

Participant milestones
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Overall Study STARTED	12	11	12
Overall Study Treated	10	11	12
Overall Study COMPLETED	8	9	6
Overall Study NOT COMPLETED	4	2	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Overall Study Adverse Event	1	0	3
Overall Study Did Not Meet Entrance Criteria	0	1	0
Overall Study Global Deterioration of Health Status	0	1	0
Overall Study Lack of Efficacy	1	0	1
Overall Study Other	0	0	2
Overall Study Randomized but not Treated	2	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=10 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=11 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=12 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Total n=33 Participants Total of all reporting groups
Age, Customized 18 to 44 years	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Age, Customized 45 to 64 years	2 participants n=5 Participants	4 participants n=7 Participants	5 participants n=5 Participants	11 participants n=4 Participants
Age, Customized greater than or equal to (>=) 65 years	8 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	21 participants n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants	18 Participants n=4 Participants

PRIMARY outcome

Timeframe: 7 to 14 days after end of treatment

Population: Clinically evaluable: all ITT participants who received at least 80% of study drug, no concomitant systemic antibiotic with activity against relevant pathogens, diagnosed with pneumonia as defined by protocol inclusion criteria, assignment of pneumonia severity index (PSI) score III (low: score range 71-90)-IV(high: score range 91-130).

Outcome measures

Outcome measures
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=10 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=8 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=8 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Percentage of Participants With Clinical Response at Test of Cure (TOC) Visit Indeterminate	0 percentage of participants	0 percentage of participants	12.5 percentage of participants
Percentage of Participants With Clinical Response at Test of Cure (TOC) Visit Cure	90.0 percentage of participants	87.5 percentage of participants	62.5 percentage of participants
Percentage of Participants With Clinical Response at Test of Cure (TOC) Visit Failure	10.0 percentage of participants	12.5 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: EOT (Day 7 to 10) , Follow-up (15 to 28 days after EOT)

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.

Outcome measures

Outcome measures
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=10 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=8 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=8 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit EOT: Cure	60.0 percentage of participants	75.0 percentage of participants	75.0 percentage of participants
Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit EOT: Improvement	30.0 percentage of participants	25.0 percentage of participants	12.5 percentage of participants
Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit EOT: Failure	10.0 percentage of participants	0.0 percentage of participants	12.5 percentage of participants
Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit Follow-up: Cure	90.0 percentage of participants	87.5 percentage of participants	62.5 percentage of participants
Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit Follow-up: Failure	0.0 percentage of participants	0.0 percentage of participants	12.5 percentage of participants
Percentage of Participants With Clinical Response at End of Treatment (EOT) and Follow-up Visit Follow-up: Indeterminate	10.0 percentage of participants	12.5 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: 7 to 14 days after EOT

Population: Microbiologic clinically evaluable population included all microbiologic ITT participants (all ITT participants in whom a pathogen was isolated at baseline) who also met criteria for the clinically evaluable subset.

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.

Outcome measures

Outcome measures
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=4 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=5 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=4 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Number of Participants With Microbiological Response at Test of Cure (TOC) Visit Eradication	4 participants	4 participants	3 participants
Number of Participants With Microbiological Response at Test of Cure (TOC) Visit Persistence	0 participants	0 participants	0 participants
Number of Participants With Microbiological Response at Test of Cure (TOC) Visit Not Applicable	0 participants	1 participants	1 participants

SECONDARY outcome

Timeframe: Baseline, TOC (7 to 14 days after end of treatment), Follow-up (15 to 28 days after EOT)

Population: Clinically evaluable population. Here 'n' signifies participants evaluable for this measure at specified time points for each arm, respectively.

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).

Outcome measures

Outcome measures
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=10 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=8 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=8 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Change From Baseline in Community Acquired Pneumonia (CAP) Symptom Questionnaire at Test of Cure (TOC) and Follow-up Visit Baseline (n=10, 8, 8)	2.17 units on a scale Standard Deviation 0.70	2.75 units on a scale Standard Deviation 1.01	2.57 units on a scale Standard Deviation 0.65
Change From Baseline in Community Acquired Pneumonia (CAP) Symptom Questionnaire at Test of Cure (TOC) and Follow-up Visit Change at TOC (n=9, 7, 6)	-1.43 units on a scale Standard Deviation 0.85	-2.02 units on a scale Standard Deviation 1.23	-1.74 units on a scale Standard Deviation 0.86
Change From Baseline in Community Acquired Pneumonia (CAP) Symptom Questionnaire at Test of Cure (TOC) and Follow-up Visit Change at Follow-up Visit (n=10, 8, 8)	-1.39 units on a scale Standard Deviation 0.86	-1.89 units on a scale Standard Deviation 1.08	-1.52 units on a scale Standard Deviation 1.00

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 15 to 28 days after EOT

Population: ITT population included all randomized participants who received at least 1 dose of double blind study drug.

Outcome measures

Outcome measures
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=10 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=11 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=12 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Number of Participants Who Died	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 15 to 28 days after EOT

Criteria for laboratory abnormalities: hemoglobin (Hb), hematocrit, red blood cell (RBC) (less than \[\<\] 0.8\*lower limit of normal \[LLN\]); reticulocyte (absolute and percentage) (\<0.5\*LLN or greater than \[\>\] 1.5\*upper LN \[ULN\]); platelet (\<0.5\*LLN or \>1.75\*ULN); white blood cell (WBC) (\<0.6\*LLN or \>1.5\*ULN); lymphocyte, neutrophil (\<0.8\*LLN or \>1.2\*ULN); eosinophil, monocyte, basophil (\>1.2\*ULN); bilirubin (BR) (\>1.5\*ULN); aspartate and alanine aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, lactate dehydrogenase (\>3.0\*ULN); total protein, albumin (\<0.8\*LLN or \>1.2\*ULN);blood urea nitrogen, creatinine (\>1.3\*ULN); sodium (\<0.95\*LLN or \>1.05\*ULN); potassium, chloride, calcium, magnesium, bicarbonate (\<0.9\*LLN or \>1.1\*ULN); glucose (\<0.6\*LLN or \>1.5\*ULN); urine (pH \[\<4.5 or \>8\], glucose, protein, blood, ketone \[\>=1\]). Total number of participants with abnormal laboratory values were reported.

Outcome measures

Outcome measures
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=10 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=11 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=11 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Number of Participants With Abnormal Laboratory Test Findings	7 participants	8 participants	9 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Last observation (up to 15-28 days after EOT, approximately 38 days)

Population: ITT population included all randomized participants who received at least 1 dose of double blind study drug.

A physical examination included an examination of the general appearance, skin, heart, head, eyes, ears, nose, throat, breasts, abdomen, musculoskeletal, neck, neurological, extremities, and others. Criteria for abnormal physical findings were based on investigator's discretion.

Outcome measures

Outcome measures
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=10 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=11 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=12 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Number of Participants With Abnormal Physical Examination Findings	0 participants	1 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 15 to 28 days after EOT

Population: ITT population included all randomized participants who received at least 1 dose of double blind study drug. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies participants evaluable for this measure for specified category for each arm, respectively.

Participants who met the categorical criteria for increase in vital signs data were reported. Categorical criteria for increase from baseline vital signs data: supine and sitting systolic blood pressure (BP) of greater than or equal to (\>=) 30 millimeter of mercury (mmHg); supine and sitting diastolic BP of \>=20 mmHg.

Outcome measures

Outcome measures
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=7 Participants Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=6 Participants Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=6 Participants Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Number of Participants With Categorical Change From Baseline in Vital Signs Sitting Systolic BP >=30 mmHg (n=7, 6, 6)	2 participants	1 participants	1 participants
Number of Participants With Categorical Change From Baseline in Vital Signs Supine Systolic BP >=30 mmHg (n=3, 5, 4)	0 participants	2 participants	1 participants
Number of Participants With Categorical Change From Baseline in Vital Signs Supine Diastolic BP >=20 mmHg (n=3, 5, 4)	0 participants	2 participants	2 participants
Number of Participants With Categorical Change From Baseline in Vital Signs Sitting Diastolic BP >=20 mmHg (n=7, 6, 6)	4 participants	1 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 0.5 to 1 hours, 1.5 to 3 hours, 3 to 5 hours after initiation of first intravenous dose; 0.5 to 2.5 hours, 4 to 6 hours following administration of oral dose on the day of IV to oral switch (minimum of 2 days equivalent on intravenous dose)

Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline up to 15 to 28 days after EOT

Population: This assessment was not performed due to the small sample size and hence data for this outcome measure is not reported.

Healthcare resource utilization was to be evaluated using the assessment of the following: date and duration of index admission, duration of hospitalization, date of discharge, location of discharge, type/length of treatment inside and outside of the hospital, healthcare professional visits outside of the hospital, emergency room visits, and other hospitalizations.

Outcome measures

Outcome data not reported

Adverse Events

Sulopenem (Single Intravenous Dose) and PF-03709270

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Sulopenem (Multi Intravenous Dose) and PF-03709270

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Ceftriaxone and Amoxicillin/Clavulanate

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sulopenem (Single Intravenous Dose) and PF-03709270 n=10 participants at risk Single loading dose of sulopenem 600 milligram (mg) intravenous infusion over 1 hour, followed by oral PF-03709270 (5\200 mg tablets) 12 hours after loading dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion), along with placebo intravenous infusion over 1 hour and then twice daily for minimum of 3 doses, followed by placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Sulopenem (Multi Intravenous Dose) and PF-03709270 n=11 participants at risk Sulopenem 600 mg intravenous infusion over 1 hour twice daily for minimum of 4 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 30 minutes once daily for minimum of 2 doses. After in-patient period, switched to oral PF-03709270 1000 mg (5\*200 mg tablets) twice daily along with oral placebo suspension twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.	Ceftriaxone and Amoxicillin/Clavulanate n=12 participants at risk Ceftriaxone 2 gram (g) intravenous infusion over 30 minutes once daily for minimum of 2 doses, followed by oral placebo tablets 12 hours after first intravenous dose, twice daily during in-patient period (minimum of 2 days equivalent on intravenous dose or as per investigator's discretion) along with placebo intravenous infusion over 1 hour twice daily for minimum of 4 doses. After in-patient period, stepped down to oral amoxicillin/clavulanate potassium suspension (800 mg/10 milliliter) twice daily along with oral placebo tablets twice daily. Total treatment duration of 7 to 10 days was at the discretion of the investigator.
Gastrointestinal disorders Enterocolitis	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 1/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Abscess limb	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pneumonia	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyothorax	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	8.3% 1/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Psychiatric disorders Suicidal ideation	0.00% 0/10 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	9.1% 1/11 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/12 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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Restriction type: OTHER