Trial Outcomes & Findings for Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia (NCT NCT01799993)
NCT ID: NCT01799993
Last Updated: 2018-07-23
Results Overview
The primary efficacy variable is Survival through the late follow-up (LFU) visit. Survival is achieved when the participant is alive through the LFU visit. No other factors are considered in the evaluation of survival.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
725 participants
Primary outcome timeframe
Up to 28-32 days after start of study treatment
Results posted on
2018-07-23
Participant Flow
To shorten the time required to obtain data from the 2 clinical studies of Amikacin Inhale Phase 3 program, Bayer and the FDA decided that the results of studies NCT01799993 and NCT00805168 should be consolidated into a single report. The studies were conducted at 166 centers across 25 countries, between 13 APR 2013 (FPFV) and 07 APR 2017 (LPLV).
A total of 807 participants were screened, of which 725 participants were randomized for the 2 studies (264 for NCT01799993 and 461 for NCT00805168), 712 participants were treated with study treatment per exposure data in EDC; 354 received aerosolized amikacin inhale and 358 received placebo.
Participant milestones
| Measure |
Amikacin Inhale (BAY41-6551)
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Overall Study
STARTED
|
362
|
363
|
|
Overall Study
ITT Population
|
354
|
358
|
|
Overall Study
mITT Population
|
255
|
253
|
|
Overall Study
COMPLETED
|
229
|
235
|
|
Overall Study
NOT COMPLETED
|
133
|
128
|
Reasons for withdrawal
| Measure |
Amikacin Inhale (BAY41-6551)
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Overall Study
Didn't complete CRF page "End of FU"
|
30
|
40
|
|
Overall Study
Death
|
61
|
45
|
|
Overall Study
Withdrawal by Subject
|
23
|
24
|
|
Overall Study
Lost to Follow-up
|
5
|
8
|
|
Overall Study
Withdrawal by parent/guardian/LAR
|
5
|
3
|
|
Overall Study
Protocol driven decision point
|
0
|
3
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Deterioration of general conditions
|
2
|
0
|
|
Overall Study
Screen failure
|
0
|
1
|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lack of Efficacy
|
1
|
0
|
|
Overall Study
Recovery
|
0
|
1
|
|
Overall Study
Logistical difficulties
|
1
|
0
|
|
Overall Study
Protocol deviation
|
1
|
0
|
|
Overall Study
Non-compliance with medical device
|
1
|
0
|
|
Overall Study
Withdrawal by parent/guardian
|
0
|
1
|
|
Overall Study
Other
|
1
|
0
|
|
Overall Study
Subject didn't return for follow-up
|
0
|
1
|
Baseline Characteristics
Inhaled Amikacin Solution BAY41-6551 as Adjunctive Therapy in the Treatment of Gram-Negative Pneumonia
Baseline characteristics by cohort
| Measure |
Amikacin Inhale (BAY41-6551)
n=354 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=358 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
Total
n=712 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.8 Years
STANDARD_DEVIATION 15.78 • n=5 Participants
|
64.1 Years
STANDARD_DEVIATION 17.04 • n=7 Participants
|
63.9 Years
STANDARD_DEVIATION 16.42 • n=5 Participants
|
|
Age, Customized
<18
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
18 to <45
|
38 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
91 Participants
n=5 Participants
|
|
Age, Customized
45 to <65
|
130 Participants
n=5 Participants
|
105 Participants
n=7 Participants
|
235 Participants
n=5 Participants
|
|
Age, Customized
65 to <75
|
92 Participants
n=5 Participants
|
83 Participants
n=7 Participants
|
175 Participants
n=5 Participants
|
|
Age, Customized
>=75
|
94 Participants
n=5 Participants
|
117 Participants
n=7 Participants
|
211 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
107 Participants
n=5 Participants
|
107 Participants
n=7 Participants
|
214 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
247 Participants
n=5 Participants
|
251 Participants
n=7 Participants
|
498 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
49 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
104 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
262 Participants
n=5 Participants
|
250 Participants
n=7 Participants
|
512 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
43 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
96 Participants
n=5 Participants
|
|
APACHE II score
<20
|
187 Participants
n=5 Participants
|
186 Participants
n=7 Participants
|
373 Participants
n=5 Participants
|
|
APACHE II score
>=20
|
167 Participants
n=5 Participants
|
172 Participants
n=7 Participants
|
339 Participants
n=5 Participants
|
|
CPIS
|
7.1 Scores on a scale
STANDARD_DEVIATION 1.38 • n=5 Participants
|
6.9 Scores on a scale
STANDARD_DEVIATION 1.29 • n=7 Participants
|
7.0 Scores on a scale
STANDARD_DEVIATION 1.34 • n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 28-32 days after start of study treatmentPopulation: Modified intent-to-treat (mITT) population (included all subjects who had a culture-confirmed Gram-negative bacteria that had been treated with at least one dose of study treatment, and had an APACHE II score ≥ 10 at the time of diagnosis of pneumonia)
The primary efficacy variable is Survival through the late follow-up (LFU) visit. Survival is achieved when the participant is alive through the LFU visit. No other factors are considered in the evaluation of survival.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=255 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=253 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants Surviving Through LFU Visit
Clinical Success (Survive)
|
191 Participants
|
196 Participants
|
|
Number of Participants Surviving Through LFU Visit
Clinical Failure (Did not survive)
|
64 Participants
|
57 Participants
|
SECONDARY outcome
Timeframe: Up to 28-32 days after start of study treatmentPopulation: Participants who died through LFU visit in mITT population set
Death through LFU visit was adjudicated as pneumonia-related or pneumonia-unrelated for participants in the amikacin inhale group and participants in the placebo group.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=64 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=57 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit
Pneumonia-related mortality
|
43 Participants
|
36 Participants
|
|
Number of Participants With Adjudicated Pneumonia-Related Death Through LFU Visit
Pneumonia-unrelated mortality
|
21 Participants
|
21 Participants
|
SECONDARY outcome
Timeframe: Up to 10 days after start of study treatmentPopulation: mITT population
Early Clinical Response was determined by the following: 1. CPIS scoring at Days 3, 5, and 10 compared to baseline (a. On Day 3, CPIS increase from baseline by at least 2 points was considered a failure. b. On Day 5, CPIS decrease from baseline of at least 1 point was not a failure. CPIS of no change from baseline was considered a failure. Any CPIS increase from baseline was a failure. c. On Day 10, CPIS decrease from baseline of at least 2 points was not a failure. CPIS decrease of only 1 point is a failure. Clinical Pulmonary Infection Score of no change was considered a failure. Any CPIS increase from baseline was a failure). 2. All-cause mortality through EOT visit was a failure. 3. The development of empyema or lung abscess through the EOT visit was a failure.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=255 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=253 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants With Early Clinical Response
Early Clinical Response - Success
|
149 Participants
|
145 Participants
|
|
Number of Participants With Early Clinical Response
Early Clinical Response - Failure
|
106 Participants
|
108 Participants
|
SECONDARY outcome
Timeframe: Up to 28-32 days after start of study treatmentPopulation: mITT population
Number of days on mechanical ventilator was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived through the LFU visit, the ventilation days were actual days on ventilation with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days on ventilator was censored at 28 days. For participants who died or discontinued off ventilation, the number of days on ventilation was actual days on ventilation with a maximum value of 28 days. For participants who died or discontinued on ventilation, the number of days on ventilation was 28 days. Further analysis of the number of days on mechanical ventilator was to be performed with censoring at Day 28 for subset of participants on ventilation without censoring.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=255 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=253 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Days on Mechanical Ventilation Through LFU Visit
|
20.6 day
Standard Deviation 10.09
|
20.2 day
Standard Deviation 10.24
|
SECONDARY outcome
Timeframe: Up to 28-32 days after start of study treatmentPopulation: mITT population without missing start or end dates
Number of days in ICU was summarized by descriptive statistics. Duration was defined as the number of days from the date of first study drug through the LFU visit. For participants who lived in ICU through the LFU visit, the ICU days were actual days in ICU with a maximum value of 28 days. For participants who died after Day 28 but on or before their LFU visit, the days in ICU was censored at 28 days. For participants who died or discontinued in ICU, the number of days in ICU was 28 days. Further analysis of the number of days in ICU was to be performed with censoring at Day 28 for subset of participants on ventilation and without censoring.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=247 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=249 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Days in the ICU Through LFU Visit
|
21.3 day
Standard Deviation 8.17
|
21.9 day
Standard Deviation 7.99
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 17-19 days after start of study treatmentPopulation: mITT population
The number of participants with microbiological response for each pathogen among the total number of participants with baseline pathogen isolates for each pathogen was determined. If a participant had 3 pathogens, all 3 were tabulated. Eradication ( defined as the absence of the original pathogen(s) at the post-treatment test-of-cure \[TOC\] visit culture of specimens from the original site of infection) and presumed eradication (defined as absence of appropriate culture material in a participant judged to be a clinical cure; he or she was unable to produce sputum and invasive procedures were not warranted) rates were reported to reveal the microbiological responses. The data were displayed for each bacterial genus/species. Baseline pathogen was defined as pathogens tested at Screening and Day 1 visit by central laboratory.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=255 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=253 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Haemophilus influenzae
|
8 Participants
|
10 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Providencia stuartii
|
0 Participants
|
1 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Serratia marcescens
|
12 Participants
|
13 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Acinetobacter
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Acinetobacter anitratus
|
46 Participants
|
43 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Achromobacter xylosoxidans
|
0 Participants
|
2 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Acinetobacter junii
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Burkholderia cepacia complex
|
1 Participants
|
1 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Chryseobacterium indologenes
|
0 Participants
|
1 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Citrobacter farmeri
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Citrobacter freundii complex
|
3 Participants
|
4 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Citrobacter koseri
|
3 Participants
|
2 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Corynebacterium argentoratense
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Corynebacterium propinquum
|
0 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Corynebacterium striatum
|
2 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Elizabethkingia meningoceptica
|
1 Participants
|
1 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Enterobacter aerogenes
|
4 Participants
|
2 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Enterobacter cloacae
|
9 Participants
|
10 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Enterococcus faecalis
|
1 Participants
|
2 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Enterococcus faecium
|
1 Participants
|
1 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Escherichia coli
|
21 Participants
|
19 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Ewingella americana
|
0 Participants
|
1 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Haemophilus parahaemolyticus
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Haemophilus parainfluenzae
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Hafnia alvei
|
1 Participants
|
2 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Kerstersia gyiorum
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Klebsiella oxytoca
|
2 Participants
|
5 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Klebsiella pneumoniae
|
38 Participants
|
28 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Kluyvera intermedia
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Moraxella catarrhalis
|
1 Participants
|
3 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Morganella morganii
|
0 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Neisseria
|
2 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Pantoea agglomerans
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Pasteurella multocida
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Proteus mirabilis
|
2 Participants
|
6 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Proteus vulgaris
|
0 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Pseudomonas aeruginosa
|
55 Participants
|
44 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Pseudomonas putida
|
0 Participants
|
1 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Raoultella ornithinolytica
|
0 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Raoultella planticola
|
3 Participants
|
2 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Serratia liquefaciens
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Staphylococcus aureus
|
12 Participants
|
10 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Staphylococcus haemolyticus
|
1 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Stenotrophomonas maltophilia
|
12 Participants
|
10 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Streptococcus agalactiae
|
2 Participants
|
2 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Streptococcus anginosus group
|
0 Participants
|
1 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Streptococcus mitis group
|
2 Participants
|
0 Participants
|
|
Number of Participants With Microbiological Response Per Pathogen at TOC Visit
Streptococcus pneumoniae
|
2 Participants
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 17-19 days after start of study treatmentPopulation: mITT population
The responses of eradication (defined as the absence of the original pathogen(s) at the post-treatment TOC culture of specimens from the original site of infection) and presumed eradication (defined as absence of appropriate culture material in a participant judged to be a clinical cure; he or she was unable to produce sputum and invasive procedures were not warranted) were tabulated for each participant to reveal the microbiological responses. All pathogen isolates from a participant must be eradicated (or presumed eradicated) to tabulate an eradicated (or presumed eradicated) response. Baseline pathogen was defined as pathogens tested at Screening and Day 1 visit by central laboratory.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=255 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=253 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants With Microbiological Response at TOC Visit
|
150 Participants
|
118 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 28-32 days after start of study treatmentPopulation: mITT population
The responses of recurrence were tabulated for each participant. Recurrence was defined as the reappearance of the original pathogen(s) from a specimen taken after the TOC visit. If one or more pathogen reappeared, all isolates from a participant were tabulated as "recurrence". Baseline pathogen was defined as pathogens tested at Screening and Day 1 visit by central laboratory.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=255 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=253 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants With Microbiological Recurrence at LFU Visit
|
12 Participants
|
12 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 10 days after start of study treatmentPopulation: mITT population
New pathogens also denoted as superinfection was defined as the isolation of a new pathogen (not the original baseline pathogen) from a specimen taken while the participant was on antibiotic therapy (Day 1 to EOT) and having a need for alternative antimicrobial therapy. Rates of emergence of any new pathogen by participant after start of study drug were summarized for each treatment group.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=255 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=253 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants With Emergence of New Respiratory Pathogens During the Aerosol Treatment Period
|
21 Participants
|
34 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 28-32 days after start of study treatmentPopulation: mITT population participants with pathogen susceptible to amikacin in pre-treatment period
Resistance to amikacin was determined for the bacterial isolates by using a standardized microbiology laboratory test that generates a minimum inhibitory concentration (MIC) for amikacin and bacterial isolate. The same microbiology resistance standard was used for all bacteria tested against amikacin. Resistant bacteria have a MIC value of 64 μg/mL or greater. Percentages of resistance were calculated based on the percentage of participants infected with any treatment-emergent pathogens resistant to amikacin. If a participant had a more than one occurrence of a specific pathogen during pre-treatment period, the worst case of testing was used.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=186 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=194 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants With Emergence of Resistance Among Pathogens
|
13 Participants
|
17 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 7 days after the end of study treatmentPopulation: ITT for Safety population (included all participants in ITT analysis set who were analyzed as treated for safety analyses)
AE was untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. AEs, occurred any time after the first dose of therapy and through 7 days after the EOT were recorded as treat-emergent AEs (TEAEs).
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=353 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=359 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants Who Received at Least One Dose of Study Drug and Reported an Adverse Event
|
295 Participants
|
303 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 7 days after the end of study treatmentPopulation: ITT for Safety population
AE was untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: AE resulting in following outcomes or deemed significant for any reason: death; life-threatening; inpatient hospitalization or prolongation of existing hospitalization; persistent; significant disability/incapacity; congenital anomaly/birth defect; medical important serious event judged by investigator. SAEs, occurred any time after the first dose of therapy and through 7 days after the EOT were recorded as treat-emergent SAEs (TESAEs).
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=353 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=359 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants Who Received at Least One Dose of Study Drug and Reported a Serious Adverse Event
|
101 Participants
|
97 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 7 days after the end of study treatmentPopulation: ITT for Safety population
The overall number of participants with any organ failure was summarized for each treatment group. Organ failure was defined by a specific organ type and by a collection of MedDRA version 20.0 preferred terms that were determined by the sponsor's clinical team. A participant with multiple AEs within a system organ class or preferred term is counted a single time for that system organ class (SOC) or preferred term.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=353 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=359 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Participants With Organ Failure
|
69 Participants
|
67 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to 10 days and 15 days after start of study treatment, respectivelyPopulation: mITT population
Number of deaths due to any reason through Day 10 and Day 15 were summarized for each treatment group.
Outcome measures
| Measure |
Amikacin Inhale (BAY41-6551)
n=255 Participants
Participants received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via Pulmonary Drug Delivery System (PDDS) Clinical from Day 1 to Day 10.
|
Placebo
n=253 Participants
Participants received 3.2 mL aerosolized placebo solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Number of Death Due to Any Reason Through Day 10 and Day 15
Number of death through Day 10
|
23 Participants
|
32 Participants
|
|
Number of Death Due to Any Reason Through Day 10 and Day 15
Number of death through Day 15
|
32 Participants
|
39 Participants
|
Adverse Events
Amikacin Inhale 400mg q12h
Serious events: 101 serious events
Other events: 207 other events
Deaths: 86 deaths
Placebo
Serious events: 97 serious events
Other events: 214 other events
Deaths: 85 deaths
Serious adverse events
| Measure |
Amikacin Inhale 400mg q12h
n=353 participants at risk
Patients received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
Placebo
n=359 participants at risk
Patients received 3.2 mL placebo solution aerosolized every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Blood and lymphatic system disorders
Coagulopathy
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Blood and lymphatic system disorders
Heparin-induced thrombocytopenia
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Acute myocardial infarction
|
0.85%
3/353 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Arrhythmia
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Atrial fibrillation
|
0.57%
2/353 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Atrioventricular block complete
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Cardiac arrest
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.84%
3/359 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Cardiac failure
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Cardiac failure acute
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Cardiogenic shock
|
0.85%
3/353 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Myocardial infarction
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Ventricular tachycardia
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Acute left ventricular failure
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Cardiovascular insufficiency
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Intestinal ischaemia
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Oesophageal perforation
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
General disorders
Pyrexia
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
General disorders
Catheter site haemorrhage
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
General disorders
Multiple organ dysfunction syndrome
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.4%
5/359 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Bacteraemia
|
0.85%
3/353 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Bronchopulmonary aspergillosis
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Infection
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Lung abscess
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Mediastinitis
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Pathogen resistance
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Peritonitis
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Pneumonia
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.4%
5/359 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Pneumonia pseudomonal
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Postoperative wound infection
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Sepsis
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.1%
4/359 • Number of events 4 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Septic shock
|
2.0%
7/353 • Number of events 7 • After the first dose of study drug and no later than 7 days after end of treatment
|
4.2%
15/359 • Number of events 15 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Urosepsis
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Pulmonary sepsis
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Lung infection
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Device related sepsis
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Bacillus bacteraemia
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Brain herniation
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Multiple injuries
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Pneumonitis chemical
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Anastomotic leak
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Vascular procedure complication
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Gastrointestinal anastomotic leak
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Injury, poisoning and procedural complications
Weaning failure
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Investigations
Respiratory rate decreased
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Investigations
Hepatic enzyme increased
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Musculoskeletal and connective tissue disorders
Muscle haemorrhage
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to lung
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Nervous system disorders
Brain hypoxia
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Nervous system disorders
Cerebral ischaemia
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Nervous system disorders
Cerebrovascular accident
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Nervous system disorders
Haemorrhagic stroke
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Nervous system disorders
Ruptured cerebral aneurysm
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Nervous system disorders
Stroke in evolution
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Psychiatric disorders
Mental status changes
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Renal and urinary disorders
Renal failure
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Renal and urinary disorders
Acute kidney injury
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.1%
4/359 • Number of events 4 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Asphyxia
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
0.57%
2/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.84%
3/359 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.1%
4/353 • Number of events 4 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia aspiration
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory acidosis
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.84%
3/359 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.28%
1/353 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.5%
9/353 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.1%
4/359 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Sputum retention
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Obstructive airways disorder
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Reexpansion pulmonary oedema
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary arterial hypertension
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial hyperreactivity
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Acute interstitial pneumonitis
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.00%
0/359 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Vascular disorders
Hypotension
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Vascular disorders
Shock
|
0.85%
3/353 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Vascular disorders
Shock haemorrhagic
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.84%
3/359 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Vascular disorders
Deep vein thrombosis
|
0.28%
1/353 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Product Issues
Device malfunction
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Product Issues
Device dislocation
|
0.00%
0/353 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.28%
1/359 • Number of events 1 • After the first dose of study drug and no later than 7 days after end of treatment
|
Other adverse events
| Measure |
Amikacin Inhale 400mg q12h
n=353 participants at risk
Patients received 400 mg (3.2 mL) aerosolized Amikacin (BAY41-6551) solution every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
Placebo
n=359 participants at risk
Patients received 3.2 mL placebo solution aerosolized every 12 hours via PDDS Clinical from Day 1 to Day 10.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
10.2%
36/353 • Number of events 38 • After the first dose of study drug and no later than 7 days after end of treatment
|
12.3%
44/359 • Number of events 49 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Blood and lymphatic system disorders
Coagulopathy
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.8%
10/359 • Number of events 11 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Atrial fibrillation
|
2.5%
9/353 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.8%
10/359 • Number of events 10 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Cardiac disorders
Tachycardia
|
1.7%
6/353 • Number of events 6 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.1%
11/359 • Number of events 11 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Constipation
|
8.5%
30/353 • Number of events 30 • After the first dose of study drug and no later than 7 days after end of treatment
|
8.9%
32/359 • Number of events 32 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
7.6%
27/353 • Number of events 30 • After the first dose of study drug and no later than 7 days after end of treatment
|
9.2%
33/359 • Number of events 34 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
3.7%
13/353 • Number of events 13 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.7%
6/359 • Number of events 6 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Gastrointestinal disorders
Vomiting
|
1.7%
6/353 • Number of events 7 • After the first dose of study drug and no later than 7 days after end of treatment
|
4.7%
17/359 • Number of events 18 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
General disorders
Oedema
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.5%
9/359 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
General disorders
Oedema peripheral
|
2.5%
9/353 • Number of events 12 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.6%
13/359 • Number of events 14 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
General disorders
Pyrexia
|
5.1%
18/353 • Number of events 21 • After the first dose of study drug and no later than 7 days after end of treatment
|
5.8%
21/359 • Number of events 24 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
3.4%
12/353 • Number of events 12 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.6%
13/359 • Number of events 13 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Septic shock
|
2.3%
8/353 • Number of events 11 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.4%
5/359 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Infections and infestations
Urinary tract infection
|
2.8%
10/353 • Number of events 11 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.8%
10/359 • Number of events 10 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Investigations
Oxygen saturation decreased
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.2%
8/359 • Number of events 10 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
2.3%
8/353 • Number of events 8 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.8%
10/359 • Number of events 11 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
4.0%
14/353 • Number of events 14 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.8%
10/359 • Number of events 10 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hypernatraemia
|
2.5%
9/353 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.3%
12/359 • Number of events 12 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.4%
5/353 • Number of events 5 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.5%
9/359 • Number of events 12 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
9.1%
32/353 • Number of events 36 • After the first dose of study drug and no later than 7 days after end of treatment
|
10.3%
37/359 • Number of events 40 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
2.3%
8/353 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.9%
7/359 • Number of events 7 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
4.8%
17/353 • Number of events 17 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.3%
12/359 • Number of events 12 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
1.7%
6/353 • Number of events 6 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.1%
11/359 • Number of events 11 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Hypoproteinaemia
|
2.3%
8/353 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.1%
4/359 • Number of events 4 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Metabolism and nutrition disorders
Metabolic alkalosis
|
2.3%
8/353 • Number of events 10 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.8%
10/359 • Number of events 10 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Psychiatric disorders
Agitation
|
2.3%
8/353 • Number of events 8 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.3%
12/359 • Number of events 12 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Psychiatric disorders
Delirium
|
4.0%
14/353 • Number of events 15 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.5%
9/359 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Psychiatric disorders
Insomnia
|
1.7%
6/353 • Number of events 6 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.1%
11/359 • Number of events 11 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Renal and urinary disorders
Oliguria
|
0.85%
3/353 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.2%
8/359 • Number of events 8 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Renal and urinary disorders
Renal impairment
|
1.1%
4/353 • Number of events 4 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.5%
9/359 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Renal and urinary disorders
Acute kidney injury
|
2.5%
9/353 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.9%
7/359 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Bronchospasm
|
2.8%
10/353 • Number of events 15 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.56%
2/359 • Number of events 2 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.0%
7/353 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
2.5%
9/359 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
3.1%
11/353 • Number of events 11 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.9%
14/359 • Number of events 14 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Vascular disorders
Hypertension
|
3.7%
13/353 • Number of events 13 • After the first dose of study drug and no later than 7 days after end of treatment
|
1.9%
7/359 • Number of events 8 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Vascular disorders
Hypotension
|
6.5%
23/353 • Number of events 24 • After the first dose of study drug and no later than 7 days after end of treatment
|
3.3%
12/359 • Number of events 12 • After the first dose of study drug and no later than 7 days after end of treatment
|
|
Vascular disorders
Deep vein thrombosis
|
2.5%
9/353 • Number of events 9 • After the first dose of study drug and no later than 7 days after end of treatment
|
0.84%
3/359 • Number of events 3 • After the first dose of study drug and no later than 7 days after end of treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The PI will not make any publication of the results of the Study before the first multi-center publication, unless otherwise agreed upon by the Parties. In the event there is no multi-center publication within eighteen (18) months after a Study has been completed or terminated as all Study sites, Institution and/or Investigator shall have the right to publish the results from the Study at the Institution subject to the guideline laid out in the contacts.
- Publication restrictions are in place
Restriction type: OTHER