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Trial record 2 of 3 for:    "Nontuberculous Mycobacterial Lung Disease" | "Anti-Infective Agents"

Liposomal Amikacin for Inhalation (LAI) for Nontuberculous Mycobacteria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01315236
Recruitment Status : Completed
First Posted : March 15, 2011
Results First Posted : August 21, 2019
Last Update Posted : August 21, 2019
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Insmed Incorporated

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Mycobacterium Infections, Nontuberculous
Interventions Drug: Liposomal amikacin for inhalation (LAI)
Drug: placebo
Enrollment 90
Recruitment Details One patient out of the 90 was randomized but not dosed.
Pre-assignment Details  
Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Period Title: Double-blind Phase
Started 44 45
Completed 40 45
Not Completed 4 0
Reason Not Completed
Death             1             0
Adverse Event             1             0
Withdrawal of Consent             1             0
Lost to Follow-up             1             0
Period Title: Open-label Phase
Started 35 [1] 43 [1]
Completed 34 41
Not Completed 1 2
Reason Not Completed
Death             1             0
Adverse Event             0             1
Other             0             1
[1]
Some subjects did not consent to the open label after the double blind phase.
Period Title: 12-Month Follow-up Period
Started 27 [1] 32 [1]
Completed 26 31
Not Completed 1 1
Reason Not Completed
Death             0             1
Did not return to the site for Month 12             1             0
[1]
Some subjects did not consent to the 12 month safety.
Arm/Group Title LAI 590 mg QD Placebo Total
Hide Arm/Group Description

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Total of all reporting groups
Overall Number of Baseline Participants 44 45 89
Hide Baseline Analysis Population Description
Double-blind Phase
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 44 participants 45 participants 89 participants
58.0  (16.61) 59.1  (15.20) 58.5  (15.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 89 participants
Female
38
  86.4%
40
  88.9%
78
  87.6%
Male
6
  13.6%
5
  11.1%
11
  12.4%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 44 participants 45 participants 89 participants
White (not of Hispanic origin)
42
  95.5%
40
  88.9%
82
  92.1%
Hispanic
0
   0.0%
2
   4.4%
2
   2.2%
African
0
   0.0%
1
   2.2%
1
   1.1%
Asian
2
   4.5%
2
   4.4%
4
   4.5%
1.Primary Outcome
Title Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84.
Hide Description The endpoint used the 7-step semi-quantitative scale (SQS) for mycobacterial culture reporting in both solid and liquid growth media, with step 1 = culture negative in both solid and liquid media, step 2 = growth in liquid medium only, 3 = solid medium positive, 4 = 50 to 100 colonies in solid medium & growth in liquid, 5 = >100 to 200 colonies in solid medium & growth in liquid, 6 = >200 to 500 colonies in solid medium & growth in liquid, 7 = >500 colonies in solid medium & growth in liquid. Full scale range is 1 (best score) to 7 (worst score). The change in step measures the growth at Day 84 compared to the growth at Baseline. The negative values represent reduction in colony growth.
Time Frame Baseline and end of double-blind phase of 84 days
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description:

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Overall Number of Participants Analyzed 44 45
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline: Culture negative
5
  11.4%
5
  11.1%
Baseline: Growth in liquid medium only
1
   2.3%
1
   2.2%
Baseline: Agar positive
17
  38.6%
10
  22.2%
Baseline: 1+ (50-100 colonies)
2
   4.5%
4
   8.9%
Baseline: 2+ (> 100-200 colonies)
2
   4.5%
2
   4.4%
Baseline: 3+ (> 200-500 colonies)
3
   6.8%
4
   8.9%
Baseline: 4+ (> 500 colonies)
14
  31.8%
19
  42.2%
Day 84: -6 steps from baseline
1
   2.3%
0
   0.0%
Day 84: -5 steps from baseline
0
   0.0%
0
   0.0%
Day 84: -4 steps from baseline
1
   2.3%
0
   0.0%
Day 84: -3 steps from baseline
3
   6.8%
0
   0.0%
Day 84: -2 steps from baseline
6
  13.6%
6
  13.3%
Day 84: -1 step from baseline
5
  11.4%
5
  11.1%
Day 84: no change from baseline
23
  52.3%
23
  51.1%
Day 84: +1 step from baseline
2
   4.5%
5
  11.1%
Day 84: +2 steps from baseline
0
   0.0%
3
   6.7%
Day 84: +3 steps from baseline
1
   2.3%
0
   0.0%
Day 84: +4 steps from baseline
1
   2.3%
2
   4.4%
Day 84: +5 steps from baseline
0
   0.0%
1
   2.2%
Day 84: +6 steps from baseline
0
   0.0%
0
   0.0%
Day 84: +7 (Death)
1
   2.3%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LAI 590 mg QD, Placebo
Comments

The primary efficacy analysis tested the following hypotheses:

  • H0: There is no difference at Day 84 between the LAI arm and the placebo arm
  • Ha: There is a difference at Day 84 between the LAI arm and the placebo arm

Statistical analysis applies to all day 84 rows.

Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments Conducted in the mITT population using a stratified Wilcoxon rank sum test, to compare the treatment arms at a 2-sided significance level of 0.05, adjusting for the randomization strata (presence/absence of CF and MAC versus Mycobacterium abscessus).
Method Wilcoxon rank sum test
Comments [Not Specified]
2.Secondary Outcome
Title Number of Subjects With Negative NTM Culture for the LAI Arm at Day 84 Compared to the Placebo Arm at Day 84
Hide Description Sputum specimens were cultured in liquid media in addition to solid media (agar). If results were negative on agar, the liquid media was held for 6 weeks before reporting as culture negative. Culture was negative when confirmed with no growth in liquid medium.
Time Frame 84 days double-blind phase
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description:

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Overall Number of Participants Analyzed 44 45
Measure Type: Count of Participants
Unit of Measure: Participants
14
  31.8%
4
   8.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LAI 590 mg QD, Placebo
Comments stratified Cochran-Mantel-Haenszel test
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
3.Secondary Outcome
Title Time to Negative NTM Culture….During the 84-day Double-blind Treatment Phase
Hide Description Sputum specimens were cultured in liquid media in addition to solid media (agar). If results were negative on agar, the liquid media was held for 6 weeks before reporting as culture negative. Culture was negative when confirmed with no growth in liquid medium.
Time Frame 84 days double-blind phase
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description:

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Overall Number of Participants Analyzed 44 45
Median (Inter-Quartile Range)
Unit of Measure: days
NA [1] 
(85.0 to NA)
NA [1] 
(NA to NA)
[1]
The median time to a negative NTM culture was not able to be estimated due to insufficient number of participants.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LAI 590 mg QD, Placebo
Comments Cox proportional hazard model
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0129
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 5.68
Confidence Interval (2-Sided) 95%
1.25 to 25.79
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Ordinal, 3-level Response From Baseline on the SQS for Mycobacterial Culture for the LAI Arm at Day 84 Compared to the Placebo Arm at Day 84
Hide Description The ordinal, 3-level response are (1) improvement (2) no change (3) worsening or death
Time Frame Baseline and end of double-blind phase of 84 days
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description:

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Overall Number of Participants Analyzed 44 45
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement (a decrease of 1 step or more)
16
  36.4%
11
  24.4%
No change
20
  45.5%
23
  51.1%
Worsening (an increase of 1 step or more) or death
5
  11.4%
11
  24.4%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LAI 590 mg QD, Placebo
Comments Ordinal Logistic Regressions Model
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.077
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Respiratory and Systemic Symptoms Questionnaire (RSSQ) Score at Day 84 for the LAI Arm Compared to the Placebo Arm
Hide Description The RSSQ was administered to gather information from the subject about the types of symptoms that the subject has experienced since the last contact. A reduction in score indicates improvement. The range of values for the scores are -2 (best) to +2 (worst) in whole numbers. The composite score was calculated by averaging the scores of the subscales.
Time Frame Baseline to day 84.
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description:

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Overall Number of Participants Analyzed 44 45
Mean (Standard Deviation)
Unit of Measure: units on a score
-0.80  (0.992) -0.60  (0.736)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LAI 590 mg QD, Placebo
Comments Stratified Wilcoxon-rank sum
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4545
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm
Hide Description The assessing physician asked the subject to rate his/her assessment of health according to the GRH. Subject responses to, “How would you rate your health at the present time?” included: Excellent, Good, Fair, or Poor.
Time Frame Baseline and end of double-blind phase of 84 days
Hide Outcome Measure Data
Hide Analysis Population Description

mITT

Subjects with missing data were excluded

Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description:

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Overall Number of Participants Analyzed 44 45
Measure Type: Count of Participants
Unit of Measure: Participants
No change: Excellent -> Excellent Number Analyzed 39 participants 45 participants
2
   5.1%
2
   4.4%
No change: Good -> Good Number Analyzed 39 participants 45 participants
15
  38.5%
21
  46.7%
No change: Fair -> Fair Number Analyzed 39 participants 45 participants
8
  20.5%
5
  11.1%
No change: Poor -> Poor Number Analyzed 39 participants 45 participants
1
   2.6%
1
   2.2%
Increase Number Analyzed 39 participants 45 participants
4
  10.3%
6
  13.3%
Increase: By 3 Categories (Poor -> Excellent) Number Analyzed 39 participants 45 participants
0
   0.0%
0
   0.0%
Increase by 2 Categories Number Analyzed 39 participants 45 participants
0
   0.0%
1
   2.2%
Increase: By 2 Categories (Poor -> Good) Number Analyzed 39 participants 45 participants
0
   0.0%
0
   0.0%
Increase: By 2 Categories (Fair -> Excellent) Number Analyzed 39 participants 45 participants
0
   0.0%
1
   2.2%
Increase by 1 Category Number Analyzed 39 participants 45 participants
4
  10.3%
5
  11.1%
Increase: By 1 Category (Poor -> Fair) Number Analyzed 39 participants 45 participants
2
   5.1%
0
   0.0%
Increase: By 1 Category (Fair -> Good) Number Analyzed 39 participants 45 participants
2
   5.1%
5
  11.1%
Increase: By 1 Category (Good -> Excellent) Number Analyzed 39 participants 45 participants
0
   0.0%
0
   0.0%
Decrease Number Analyzed 39 participants 45 participants
9
  23.1%
10
  22.2%
Decrease: By 3 Categories (Excellent --> Poor) Number Analyzed 39 participants 45 participants
0
   0.0%
0
   0.0%
Decrease: By 2 Categories Number Analyzed 39 participants 45 participants
0
   0.0%
0
   0.0%
Decrease: By 2 Categories (Excellent -> Fair) Number Analyzed 39 participants 45 participants
0
   0.0%
0
   0.0%
Decrease: By 2 Categories (Good -> Poor) Number Analyzed 39 participants 45 participants
0
   0.0%
0
   0.0%
Decrease: By 1 Category Number Analyzed 39 participants 45 participants
9
  23.1%
10
  22.2%
Decrease: By 1 Category (Excellent -> Good) Number Analyzed 39 participants 45 participants
2
   5.1%
0
   0.0%
Decrease: By 1 Category (Good -> Fair) Number Analyzed 39 participants 45 participants
5
  12.8%
7
  15.6%
Decrease: By 1 Category (Fair -> Poor) Number Analyzed 39 participants 45 participants
2
   5.1%
3
   6.7%
7.Secondary Outcome
Title Number of Participants Requiring “Rescue” Anti-mycobacterial or Other “Rescue” Drugs During the 84-day Double-blind Phase
Hide Description Per the study protocol, study subjects were on a stable, multi-drug, anti-mycobacterial regimen based on the 2007 ATS/IDSA Guidelines; the regimen should not have changed during the study period except for safety concerns. The need for changes to the concurrent anti-mycobacterial regimen or “rescue” therapy was at the discretion of the Investigator and was tracked as a study outcome.
Time Frame 84 days double-blind phase
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description:

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Overall Number of Participants Analyzed 44 45
Measure Type: Number
Unit of Measure: participants
21 11
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LAI 590 mg QD, Placebo
Comments Cox Proportional Hazard Model
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0076
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 2.69
Confidence Interval (2-Sided) 95%
1.28 to 5.64
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Subject for “Rescue” Anti-mycobacterial or Other “Rescue” Drugs During the 84-day Double-blind Phase
Hide Description Per the study protocol, study subjects were on a stable, multi-drug, anti-mycobacterial regimen based on the 2007 ATS/IDSA Guidelines; the regimen should not have changed during the study period except for safety concerns. The need for changes to the concurrent anti-mycobacterial regimen or “rescue” therapy was at the discretion of the Investigator and was tracked as a study outcome.
Time Frame 84 days double-blind phase
Hide Outcome Measure Data
Hide Analysis Population Description
mITT
Arm/Group Title LAI 590 mg QD Placebo
Hide Arm/Group Description:

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.
Overall Number of Participants Analyzed 44 45
Measure Type: Number
Unit of Measure: participants
Number of subjects with the event 21 11
Number censored 23 34
Time Frame Up to Day 196 (84 days double-blind phase + 84 days open label phase + 28 days post discontinuation of study drug). Adverse events (AEs) were not collected during the 12-month follow-up period..
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title LAI 590 mg QD - Double Blind Placebo - Double Blind LAI 590 mg QD - Open Label Placebo - Open Label
Hide Arm/Group Description

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

  • 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.
  • Administration time is approximately 13 minutes.
  • Liposomal amikacin for inhalation will be administered for 84 days in the double-blind, randomized portion of the study.
  • Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

  • Administration procedures, volume and administration time are similar to LAI.
  • Placebo will be administered for 84 days only during the double-blind, randomized portion of the study.

LAI 590 mg QD

Liposomal amikacin for inhalation (LAI): - Liposomal amikacin for inhalation is provided as a sterile aqueous liposomal dispersion for inhalation via nebulization.

- 590 mg of liposomal amikacin for inhalation is administered once daily using the PARI Investigational eFlow® Nebulizer.

Subjects can continue with 84 additional days of dosing in the open label extension.

placebo QD

placebo: - Placebo is provided as a sterile aqueous lipid dispersion for inhalation via nebulization.

Subjects can continue with 84 additional days of dosing in the open label extension.

All-Cause Mortality
LAI 590 mg QD - Double Blind Placebo - Double Blind LAI 590 mg QD - Open Label Placebo - Open Label
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/44 (2.27%)      0/45 (0.00%)      1/35 (2.86%)      0/43 (0.00%)    
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LAI 590 mg QD - Double Blind Placebo - Double Blind LAI 590 mg QD - Open Label Placebo - Open Label
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/44 (18.18%)      4/45 (8.89%)      5/35 (14.29%)      5/43 (11.63%)    
Cardiac disorders         
Supraventricular tachycardia  1  1/44 (2.27%)  1 0/45 (0.00%)  0 0/35 (0.00%)  0 1/43 (2.33%)  1
Acute coronary syndrome  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 0/43 (0.00%)  0
Ear and labyrinth disorders         
Vertigo  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 0/43 (0.00%)  0
Gastrointestinal disorders         
Small intestinal obstruction  1  0/44 (0.00%)  0 1/45 (2.22%)  1 0/35 (0.00%)  0 0/43 (0.00%)  0
Intestinal ischaemia  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 0/43 (0.00%)  0
General disorders         
Multi-organ failure  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 0/43 (0.00%)  0
Infections and infestations         
Infective exacerbation of bronchiectasis  1  2/44 (4.55%)  2 1/45 (2.22%)  1 0/35 (0.00%)  0 0/43 (0.00%)  0
Pneumonia  1  1/44 (2.27%)  1 2/45 (4.44%)  2 0/35 (0.00%)  0 0/43 (0.00%)  0
Gastroenteritis viral  1  1/44 (2.27%)  1 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Infective pulmonary exacerbation of cystic fibrosis  1  1/44 (2.27%)  1 0/45 (0.00%)  0 2/35 (5.71%)  2 3/43 (6.98%)  3
Urinary Tract Infection  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 0/43 (0.00%)  0
Urosepsis  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 0/43 (0.00%)  0
Injury, poisoning and procedural complications         
Femur fracture  1  1/44 (2.27%)  1 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Humerus fracture  1  1/44 (2.27%)  1 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Metabolism and nutrition disorders         
Dehydration  1  1/44 (2.27%)  1 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Acute respiratory distress syndrome  1  1/44 (2.27%)  1 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Eosinophilic pneumonia  1  0/44 (0.00%)  0 1/45 (2.22%)  1 0/35 (0.00%)  0 0/43 (0.00%)  0
Haemoptysis  1  1/44 (2.27%)  1 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Respiratory disorder  1  1/44 (2.27%)  1 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Pneumonitis  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 1/43 (2.33%)  1
Vascular disorders         
Deep Vein Thrombosis  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 0/43 (0.00%)  0
1
Term from vocabulary, MedDRA 15.0
Indicates events were collected by systematic assessment
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Frequency Threshold for Reporting Other Adverse Events 5%
LAI 590 mg QD - Double Blind Placebo - Double Blind LAI 590 mg QD - Open Label Placebo - Open Label
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   41/44 (93.18%)      39/45 (86.67%)      31/35 (88.57%)      42/43 (97.67%)    
Ear and labyrinth disorders         
Ear pain  1  3/44 (6.82%)  3 0/45 (0.00%)  0 3/35 (8.57%)  4 0/43 (0.00%)  0
Gastrointestinal disorders         
Nausea  1  5/44 (11.36%)  5 4/45 (8.89%)  4 3/35 (8.57%)  3 5/43 (11.63%)  6
Abdominal discomfort  1  3/44 (6.82%)  3 0/45 (0.00%)  0 2/35 (5.71%)  2 0/43 (0.00%)  0
Diarrhoea  1  0/44 (0.00%)  0 3/45 (6.67%)  3 1/35 (2.86%)  1 4/43 (9.30%)  5
General disorders         
Fatigue  1  7/44 (15.91%)  8 4/45 (8.89%)  4 0/35 (0.00%)  0 0/43 (0.00%)  0
Pyrexia  1  4/44 (9.09%)  5 3/45 (6.67%)  6 3/35 (8.57%)  4 1/43 (2.33%)  1
Chest discomfort  1  5/44 (11.36%)  5 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Infections and infestations         
Infective exacerbation of bronchiectasis  1  17/44 (38.64%)  21 9/45 (20.00%)  9 9/35 (25.71%)  9 15/43 (34.88%)  16
Pneumonia  1  2/44 (4.55%)  2 3/45 (6.67%)  3 0/35 (0.00%)  0 0/43 (0.00%)  0
Infective pulmonary exacerbation of cystic fibrosis  1  3/44 (6.82%)  3 1/45 (2.22%)  1 4/35 (11.43%)  5 6/43 (13.95%)  8
Laryngitis  1  3/44 (6.82%)  3 1/45 (2.22%)  1 1/35 (2.86%)  1 4/43 (9.30%)  4
Nasopharyngitis  1  3/44 (6.82%)  3 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Upper Respiratory Tract Infection  1  0/44 (0.00%)  0 0/45 (0.00%)  0 1/35 (2.86%)  1 3/43 (6.98%)  3
Oral Candidiasis  1  0/44 (0.00%)  0 0/45 (0.00%)  0 0/35 (0.00%)  0 3/43 (6.98%)  3
Urinary Tract Infection  1  0/44 (0.00%)  0 0/45 (0.00%)  0 3/35 (8.57%)  3 0/43 (0.00%)  0
Nervous system disorders         
Headache  1  3/44 (6.82%)  4 3/45 (6.67%)  7 2/35 (5.71%)  2 5/43 (11.63%)  5
Aphonia  1  0/44 (0.00%)  0 0/45 (0.00%)  0 2/35 (5.71%)  3 2/43 (4.65%)  2
Psychiatric disorders         
Insomnia  1  3/44 (6.82%)  3 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Dysphonia  1  19/44 (43.18%)  25 4/45 (8.89%)  4 3/35 (8.57%)  3 12/43 (27.91%)  12
Cough  1  14/44 (31.82%)  17 6/45 (13.33%)  6 3/35 (8.57%)  3 8/43 (18.60%)  10
Oropharyngeal pain  1  9/44 (20.45%)  9 1/45 (2.22%)  1 3/35 (8.57%)  6 3/43 (6.98%)  3
Haemoptysis  1  4/44 (9.09%)  4 5/45 (11.11%)  6 5/35 (14.29%)  5 5/43 (11.63%)  5
Wheezing  1  4/44 (9.09%)  4 1/45 (2.22%)  1 0/35 (0.00%)  0 0/43 (0.00%)  0
Dyspnoea  1  3/44 (6.82%)  4 1/45 (2.22%)  2 0/35 (0.00%)  0 4/43 (9.30%)  4
Nasal congestion  1  3/44 (6.82%)  3 0/45 (0.00%)  0 0/35 (0.00%)  0 0/43 (0.00%)  0
1
Term from vocabulary, MedDRA 15.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Per the signed Investigator Agreement in the protocol and protocol amendments, the PI agreed that the information presented in the study protocol is confidential, and assured that no information based on the conduct of the study was released without prior Insmed Incorporated Consent, unless the requirement is superseded by the Food and Drug Administration or other regulatory authority.
Results Point of Contact
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Name/Title: Kevin Mange (Senior VP, Clinical Development)
Organization: Insmed Incorporated
Phone: 908-947-2651
EMail: kevin.mange@insmed.com
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Responsible Party: Insmed Incorporated
ClinicalTrials.gov Identifier: NCT01315236     History of Changes
Other Study ID Numbers: TR02-112
First Submitted: March 11, 2011
First Posted: March 15, 2011
Results First Submitted: April 3, 2019
Results First Posted: August 21, 2019
Last Update Posted: August 21, 2019