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

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT01021436

Collaborator

Nektar Therapeutics (Industry)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Pneumonia	Drug: Amikacin inhalation solution (BAY41-6551)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

Aug 1, 2007

Actual Study Completion Date :

Aug 1, 2007

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Cmax [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]
Maximum serum amikacin concentration observed from time 0 to 12 h
Tmax [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]
Time that Cmax occurred
AUC0-12h [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]
Area under the serum amikacin concentration vs time curve from time 0 to 12 h
Xu0-12h [On 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
Xu12-24h [On 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
Xu0-24h [On 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 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

Number of participants with adverse events [Approximately 6 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Birminghan	Alabama	United States	35233
2	Cincinnati	Ohio	United States	45267
3	Memphis	Tennessee	United States	38163
4	Houston	Texas	United States	77030
5	Paris	Cedex 13	France	75651
6	Limoges	Cedex	France	87046