A Study to Assess the Pharmacokinetic Profile, the Safety, and the Tolerability of ME1100 Inhalation Solution in Patients With Mechanically Ventilated Bacterial Pneumonia

Recruitment & Eligibility

Inclusion Criteria

Participants must meet all of the following inclusion criteria in order to be eligible for the study:

Is a hospitalized male or female, ≥ 18 years of age at the Screening Visit;
Is on mechanical ventilation;
Has a known or suspected mechanically ventilated bacterial pneumonia with at least 1 of the following:
- Fever (> 38.5ﾟC or > 101.3ﾟF);
- Hypothermia (≤ 35.0ﾟC or ≤ 95.0ﾟF);
- Leukopenia (≤ 4500 cells/mm3);
- Leukocytosis (≤ 10000 cells/mm3);
- White blood cell count with left shift defined as > 15% immature polymorphonuclear leukocytes (bands) on peripheral blood smear; or
- Procalcitonin > 0.25 µg/mL;
Plus at least 2 of the following:
- Respiratory failure requiring mechanical ventilation;
- New onset of expectorated or suctioned purulent sputum production or respiratory secretions, or a change in the character of sputum;
- Auscultatory findings on pulmonary examination of rales and/or evidence of pulmonary consolidation;
- Dyspnea, tachypnea, or signs of respiratory distress as evidenced by an increase in respiratory support or oxygen requirement, particularly if any or all of these are progressive in nature; or
- Hypoxemia by pulse oximetry or arterial blood gas requiring an increase in supplemental oxygen;
Has a chest X-ray with a new consolidation consistent with pneumonia or significant worsening of previous findings consistent with pneumonia; and
Has an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and ≤ 30 at the Screening Visit.

Exclusion Criteria

Participants who meet any of the following exclusion criteria will not be enrolled in the study:

Has a requirement of inhaled non-study antibiotic;
Has been treated with any inhaled antibiotic (including inhaled aminoglycosides) within 72 hours of study entry;
Has renal insufficiency at Screening as evidenced by an estimated creatinine clearance <50 mL/min based on the Cockcroft-Gault formula;
Is at risk of rapidly fatal illness and death within the next 72 hours;
Is a pregnant or nursing female. Females of childbearing potential must have a serum pregnancy test prior to enrollment. If results of the serum pregnancy test are not available prior to the Day 1 Treatment Visit, the patients may be enrolled on the basis of a negative urine pregnancy test; however, the results of the serum pregnancy test must still be obtained. If either test is positive, the patients must be excluded;
Has myasthenia gravis, parkinsonism, or any other progressive neuromuscular disorder;
Has a history of epilepsy or known seizure disorder;
Has a history of sensorineural hearing loss resulting from any therapy known as ototoxic (eg, aminoglycosides, cisplatin, loop diuretics, or quinine);
Has received any investigational medication in the last 30 days (or 5 half-lives of the investigational medication, whichever is longer) prior to the Screening Visit; or
Has known hypersensitivity to ME1100, aminoglycosides, or any of the specified Best Available Therapy agents or their excipients.

Study & Design

Arm && Interventions

Group	Intervention	Description
Low dose of ME1100	ME1100 inhalation solution	-
High dose of ME1100	ME1100 inhalation solution	-

Primary Outcome Measures

Name	Time	Method
Arbekacin concentrations in respiratory fluids collected via bronchoalveolar lavage (BAL) for epithelial lining fluid (ELF)	Day 3
Plasma arbekacin concentrations	Day 1 to Day 5
Urinary elimination of arbekacin	Day 2
Arbekacin concentrations in tracheal aspirate	Day 2

Secondary Outcome Measures

Name	Time	Method
Number of participants with adverse events	Screening through 14 days after the end of treatment

Recruitment & Eligibility