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

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.

Time frame: 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).

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).

Time frame: 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.

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.

Time frame: 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.

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.

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

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).

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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.

Time frame: 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.

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

Time frame: 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)