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

Phase 2
Completed
Conditions
Pneumonia
Interventions
Registration Number
NCT01021436
Lead Sponsor
Bayer
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
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.
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Amikacin inhalation solutionAmikacin inhalation solution (BAY41-6551)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
Primary Outcome Measures
NameTimeMethod
CmaxPre-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

Maximum serum amikacin concentration observed from time 0 to 12 h

TmaxPre-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

Time that Cmax occurred

AUC0-12hPre-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

Area under the serum amikacin concentration vs time curve from time 0 to 12 h

Xu0-12hOn Day 3 at the start of dose and up to 12 h after both first and second dose

Amount of amikacin excreted in urine from 0 to 12 h after dosing

Xu12-24hOn Day 3 at the start of dose and up to 12 h after both first and second dose

Amount of amikacin excreted in urine from 12 to 24 h after dosing

Xu0-24hOn Day 3 at the start of dose and up to 12 h after both first and second dose

Amount of amikacin excreted in urine from 0 to 24 h after dosing

Tracheal aspirateDay 3
Epithelial lining fluid (ELF) concentrationApproximately 15-30 min after completion of the morning dose of study medication on Day 3
Secondary Outcome Measures
NameTimeMethod
Number of participants with adverse eventsApproximately 6 weeks
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