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

Study Overview

• Status: Completed
• Conditions: Pneumonia
• Intervention / Treatment: Drug: Amikacin inhalation solution (BAY41-6551)

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Cedex
    • Limoges, Cedex, France, 87046
  • Cedex 13
    • Paris, Cedex 13, France, 75651
• United States
  • Alabama
    • Birminghan, Alabama, United States, 35233
  • Ohio
    • Cincinnati, Ohio, United States, 45267
  • Tennessee
    • Memphis, Tennessee, United States, 38163
  • Texas
    • Houston, Texas, United States, 77030

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amikacin inhalation solution; 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); Daily dose of 800 mg of aerosolized amikacin delivered in two divided doses of 400 mg per aerosol treatment 12 hour

What is the study measuring?

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	Time Frame
Number of participants with adverse events	Approximately 6 weeks

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Nektar Therapeutics

Publications and helpful links

General Publications

• Luyt CE, Clavel M, Guntupalli K, Johannigman J, Kennedy JI, Wood C, Corkery K, Gribben D, Chastre J. Pharmacokinetics and lung delivery of PDDS-aerosolized amikacin (NKTR-061) in intubated and mechanically ventilated patients with nosocomial pneumonia. Crit Care. 2009;13(6):R200. doi: 10.1186/cc8206. Epub 2009 Dec 10.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): August 1, 2007

Study Registration Dates

• First Submitted: November 25, 2009
• First Submitted That Met QC Criteria: November 25, 2009
• First Posted (Estimate): November 30, 2009

Study Record Updates

• Last Update Posted (Estimate): February 18, 2016
• Last Update Submitted That Met QC Criteria: February 17, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Pneumonia; Gram-negative bacteria
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Anti-Infective Agents; Anti-Bacterial Agents; Amikacin
• Other Study ID Numbers: 06-IN-AK004; 2006-005079-17 (EudraCT Number)