Urease Breath Test for Rapid Characterization of Pneumonia

This is a Phase 1, open-label evaluation of an inhaled 13C-urea breath test in the identification of urease positive bacteria in patients diagnosed with pneumonia in the emergency department (ED). This study will enroll up to 75 adult male and female subjects in two cohorts. Adult subjects will be screened for participation in two dosing cohorts to be enrolled sequentially. Cohort A will enroll 15 subjects presenting to the ED with clinical concern for pneumonia and plan for outpatient treatment. Following enrollment and review of the safety of dosing in Cohort A, subjects receiving a diagnosis of pneumonia in the ED that are planned for admission will be screened for enrollment in Cohort B. Eligible subjects will provide informed consent, medical history, and samples for laboratory testing (including pregnancy testing for females of childbearing potential) during screening. Subjects will be evaluated for their CURB-65 Pneumonia Severity Score, and Community-Acquired Pneumonia Severity Index (PSI) where required data are available.

Prior to breath test administration, subjects will provide a sputum sample for bacterial culture; sample may be induced, or collected as part of initial ED workup if appropriate culture has been ordered. Subjects will undergo breath test with collection of baseline breath samples (up to 6), followed by complete nebulization of 13C-urea solution. Immediately following the end of nebulization, breath collection bag samples will be collected at up to 6 time points with at least 1 minute intervals within 10 minutes post-nebulization. Exhaled breath bags will be centrally processed to determine the change in exhaled 13CO2 levels. Vital signs, including resting blood pressure, resting pulse, respiratory rate, peripheral oxygen saturation, and temperature will be collected prior to, and following completion of, nebulization treatment. In the event of bronchospasm, during or following nebulization, albuterol rescue will be available for treatment at the discretion of the investigator.

Once required tests are complete, the subject will be treated/followed according to standard institutional protocol/practice. The subjects' clinical course will be followed for at least 24 hours, where possible, to document the final diagnosis and outcome.

Inclusion criteria

• Cohort A Only: be a man or woman age 18-65, inclusive, with suspected bacterial pneumonia on presentation to the ED based on clinical signs and symptoms AND be planned for outpatient treatment

OR

Cohort B Only: be a man or woman age 18-85, inclusive, with a diagnosis of suspected bacterial pneumonia in the ED based on findings of a positive chest x-ray and clinical signs and symptoms AND be planned for admission to the hospital ward/floor

• be capable of providing a spontaneous or induced sputum sample for analysis
• be capable of completing the breath test according to the clinical judgement of the investigator
• be able to understand the study procedures, agree to participate in the study program, and voluntarily provide written informed consent

Exclusion criteria

• have a known allergy to urea or any excipient in the nebulized solution
• be pregnant or have a positive urine pregnancy test
• have evidence of active oral infection, such as abscess or dense exudate, that requires antibiotic therapy
• have known diagnosis of cystic fibrosis or bronchiectasis
• have a known or suspected acute asthma exacerbation on presentation to the ED
• have received treatment with oral or intravenous (IV) antibiotics in the preceding 2 days prior to screening, unless antibiotic failure is suspected

OR

have received treatment in the ED with oral or IV antibiotics greater than 4 hours prior to breath test

• have an acute illness or other condition that, as determined by the investigator, would preclude participation in the study