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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Pneumonia

Intervention / Treatment
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* Drug: Amikacin inhalation solution (BAY41-6551)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amikacin inhalation solution<br>Subjects received 125 mg/mL of aerosolized amikacin via the PDDS clinical device at a nominal dose of 400 mg every 12 h for 7-14 days | Drug: Amikacin inhalation solution (BAY41-6551)<br>* Daily dose of 800 mg of aerosolized amikacin delivered in two divided doses of 400 mg per aerosol treatment 12 hour<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum serum amikacin concentration observed from time 0 to 12 h | Pre-dose and up to 12 h post-dose after the start of dosing and also at 1 h and 12 h after the administration of the second dose | 
| Tmax | Time that Cmax occurred | Pre-dose and up to 12 h post-dose after the start of dosing and also at 1 h and 12 h after the administration of the second dose | 
| AUC0-12h | Area under the serum amikacin concentration vs time curve from time 0 to 12 h | Pre-dose and up to 12 h post-dose after the start of dosing and also at 1 h and 12 h after the administration of the second dose | 
| Xu0-12h | Amount of amikacin excreted in urine from 0 to 12 h after dosing | On Day 3 at the start of dose and up to 12 h after both first and second dose | 
| Xu12-24h | Amount of amikacin excreted in urine from 12 to 24 h after dosing | On Day 3 at the start of dose and up to 12 h after both first and second dose | 
| Xu0-24h | Amount of amikacin excreted in urine from 0 to 24 h after dosing | On Day 3 at the start of dose and up to 12 h after both first and second dose | 
| Tracheal aspirate |  | Day 3 | 
| Epithelial lining fluid (ELF) concentration |  | Approximately 15-30 min after completion of the morning dose of study medication on Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | Approximately 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumonia, Gram-negative bacteria