Safety, Tolerability and Pharmacokinetics of Aerosolized Amikacin in Intubated and Mechanically-ventilated Patients With Nosocomial Pneumonia

An Open-Label, Multicenter, Multinational Study to Assess the Safety,Tolerability and Pharmacokinetics of Aerosolized Amikacin Delivered Via the Pulmonary Drug Delivery System (NKTR-061) in Intubated and Mechanically- Ventilated Patients With Nosocomial Pneumonia

This study is to understand how the inhaled form of amikacin is spread throughout the human body and how it is eliminated from the body and to make sure that giving an inhaled form of Amikacin to patients is safe and well tolerated

Inclusion Criteria:

• Male or female subjects with confirmed pneumonia, defined as the presence of a new progressive infiltrate(s) on chest radiograph and the presence of gram-negative organism by either culture or Gram stain of respiratory secretions. The subject must be intubated and mechanically ventilated and expected to remain so for at least 3 days after the start of study treatment. Subjects with a tracheostomy were also eligible.

Exclusion Criteria:

• Subjects with compromised or suppressed Immune systems, severe hypoxemia, neutropenia, serum creatinine > 2mg/dl and chronic liver disease
• Had primary lung cancer or another malignancy metastatic to the lungs
• Were known or suspected to have active tuberculosis, cystic fibrosis, acquired immunodeficiency syndrome, or Pneumocystis carinii pneumonia
• Were receiving immunosuppressive therapy, defined as chronic treatment with known immunosuppressant medications
• Had a body mass index of ≥30 kg/m2
• Had burns >40% of total body surface area
• Had known local or systemic hypersensitivity to amikacin or aminoglycosides
• Had a diagnosis of end-stage renal failure or were currently on dialysis treatment
• Had a serum albumin level <2 g/dL at Screening
• Used amikacin by any route within 7 days before the start of study treatment
• Had a presence of any concomitant condition that, in the opinion of the investigator, would preclude completion of study evaluations or make it unlikely that the contemplated course of therapy and Follow-Up could be completed
• Had known respiratory colonization with amikacin-resistant gram-negative rods