1 SYNOPSIS

Title Objectives A Phase 3 Randomized Double-Blind Study Comparing Study Drug XX. The primary objective is to determine the within 28 days after randomization Secondary objectives: To compare To compare the within 14 days after randomization in To compare the safety profile of Study Drug To assess the population pharmacokinetic (PK) profile of Study Drug XX

Methodology/ Study Design

This is a randomized, double-blind, double-dummy, multicenter, global Phase 3 study of Study Drug XX 200 mg IV 600 mg IV every 12 hours for 10 The Sponsor ( Approximately 300 sites will participate in this global study.

Number of Patients Inclusion Criteria

Approximately ___ patients will be randomized to include ___ evaluable patients

Exclusion Criteria

Patients who meet any of the following criteria are not eligible to participate in this study: 1 1.

Test Product(s), Dose, Mode of Administration, and Duration of Treatment

Duration of Study

Safety Variables Efficacy Outcomes

PK Variables Analysis Sets

Statistical Methods

Appendix A Schedule of Study Procedures

Study Day Study Visits End of Therapy (EOT; 1-3 days after last study drug) 4-10/14a Test of Cure (TOC; 7-14 days after last study drug) Late Follow-Up b (28-32 days after randomization)

Study Procedure

Informed consent (before any study procedures) Verify patient meets inclusion and exclusion criteria Record relevant medical/surgical history (5 years) Record height (estimate if necessary) and weight Perform 12-lead electrocardiogram Determine NYHA class, APACHE Obtain chest x-ray or CT scan Randomize via IVRS Record most abnormal pulse oximetry Record most abnormal minute ventilation and FiO2 Obtain partial pressure of arterial O2 and blood pH from arterial blood gas

Screening (within 24 hours of Day 1) X X X X X X X X X X X

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analysis, if clinically required Determine CPIS and SOFA scores Perform a physical examination c Record prior and/or concomitant medications Perform a chest examination and VNPrelated signs and symptoms assessment Record most abnormal vital signs e Record temperature f Obtain lower respiratory tract or pleural fluid microbiological specimens Collect blood sample for microbiology h Collect urine sample (urinalysis and Legionella antigen) Collect sample for pregnancy test i Collect blood sample for procalcitonin Collect blood samples for chemistry and hematology panels Collect blood samples for PK analysisk Collect blood sample for coagulation panel Calculate PT or INR;

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X X X X X (on-site visit only) X (on-site visit only)

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Xj X X

X X X X (on-site visit only)

Child-Pugh; estimate CLcr Administer study drug Select or re-evaluate gramnegative adjunctive therapy based on microbiology and susceptibility results Determine Investigators assessment of response Determine survival status Assess adverse events (pretreatment, treatmentemergent, or ongoing) X X l X X X X X X X

X X

Abbreviations: