Trial Outcomes & Findings for Liposomal Amikacin for Inhalation (LAI) for Nontuberculous Mycobacteria (NCT NCT01315236)

Last Updated: 2019-08-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

90 participants

Primary outcome timeframe

Baseline and end of double-blind phase of 84 days

Results posted on

2019-08-21

Participant Flow

One patient out of the 90 was randomized but not dosed.

Participant milestones

Participant milestones
Measure	LAI 590 mg QD 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 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.
Double-blind Phase STARTED	44	45
Double-blind Phase COMPLETED	40	45
Double-blind Phase NOT COMPLETED	4	0
Open-label Phase STARTED	35	43
Open-label Phase COMPLETED	34	41
Open-label Phase NOT COMPLETED	1	2
12-Month Follow-up Period STARTED	27	32
12-Month Follow-up Period COMPLETED	26	31
12-Month Follow-up Period NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	LAI 590 mg QD 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 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.
Double-blind Phase Death	1	0
Double-blind Phase Adverse Event	1	0
Double-blind Phase Withdrawal of Consent	1	0
Double-blind Phase Lost to Follow-up	1	0
Open-label Phase Death	1	0
Open-label Phase Adverse Event	0	1
Open-label Phase Other	0	1
12-Month Follow-up Period Death	0	1
12-Month Follow-up Period Did not return to the site for Month 12	1	0

Baseline Characteristics

Liposomal Amikacin for Inhalation (LAI) for Nontuberculous Mycobacteria

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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 n=89 Participants Total of all reporting groups
Age, Continuous	58.0 years STANDARD_DEVIATION 16.61 • n=5 Participants	59.1 years STANDARD_DEVIATION 15.20 • n=7 Participants	58.5 years STANDARD_DEVIATION 15.83 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	40 Participants n=7 Participants	78 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized White (not of Hispanic origin)	42 Participants n=5 Participants	40 Participants n=7 Participants	82 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized African	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and end of double-blind phase of 84 days

Population: mITT

Outcome measures

Outcome measures
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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.
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Baseline: Culture negative	5 Participants	5 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Baseline: Growth in liquid medium only	1 Participants	1 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Baseline: Agar positive	17 Participants	10 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Baseline: 1+ (50-100 colonies)	2 Participants	4 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Baseline: 2+ (> 100-200 colonies)	2 Participants	2 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Baseline: 3+ (> 200-500 colonies)	3 Participants	4 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Baseline: 4+ (> 500 colonies)	14 Participants	19 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: -6 steps from baseline	1 Participants	0 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: -5 steps from baseline	0 Participants	0 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: -4 steps from baseline	1 Participants	0 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: -3 steps from baseline	3 Participants	0 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: -2 steps from baseline	6 Participants	6 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: -1 step from baseline	5 Participants	5 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: no change from baseline	23 Participants	23 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: +1 step from baseline	2 Participants	5 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: +2 steps from baseline	0 Participants	3 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: +3 steps from baseline	1 Participants	0 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: +4 steps from baseline	1 Participants	2 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: +5 steps from baseline	0 Participants	1 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: +6 steps from baseline	0 Participants	0 Participants
Change in Semi-Quantitative Mycobacterial Culture Results From Baseline to Day 84. Day 84: +7 (Death)	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 84 days double-blind phase

Population: mITT

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.

Outcome measures

Outcome measures
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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.
Number of Subjects With Negative NTM Culture for the LAI Arm at Day 84 Compared to the Placebo Arm at Day 84	14 Participants	4 Participants

SECONDARY outcome

Timeframe: 84 days double-blind phase

Population: mITT

Outcome measures

Outcome measures
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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.
Time to Negative NTM Culture….During the 84-day Double-blind Treatment Phase	NA days Interval 85.0 to The median time to a negative NTM culture was not able to be estimated due to insufficient number of participants.	NA days The median time to a negative NTM culture was not able to be estimated due to insufficient number of participants.

SECONDARY outcome

Timeframe: Baseline and end of double-blind phase of 84 days

Population: mITT

The ordinal, 3-level response are (1) improvement (2) no change (3) worsening or death

Outcome measures

Outcome measures
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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.
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 Improvement (a decrease of 1 step or more)	16 Participants	11 Participants
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 No change	20 Participants	23 Participants
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 Worsening (an increase of 1 step or more) or death	5 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline to day 84.

Population: mITT

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.

Outcome measures

Outcome measures
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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.
Change From Baseline in Respiratory and Systemic Symptoms Questionnaire (RSSQ) Score at Day 84 for the LAI Arm Compared to the Placebo Arm	-0.80 units on a score Standard Deviation 0.992	-0.60 units on a score Standard Deviation 0.736

SECONDARY outcome

Timeframe: Baseline and end of double-blind phase of 84 days

Population: mITT Subjects with missing data were excluded

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.

Outcome measures

Outcome measures
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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.
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm No change: Excellent -> Excellent	2 Participants	2 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm No change: Good -> Good	15 Participants	21 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm No change: Fair -> Fair	8 Participants	5 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm No change: Poor -> Poor	1 Participants	1 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase	4 Participants	6 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase: By 3 Categories (Poor -> Excellent)	0 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase by 2 Categories	0 Participants	1 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase: By 2 Categories (Poor -> Good)	0 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase: By 2 Categories (Fair -> Excellent)	0 Participants	1 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase by 1 Category	4 Participants	5 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase: By 1 Category (Poor -> Fair)	2 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase: By 1 Category (Fair -> Good)	2 Participants	5 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Increase: By 1 Category (Good -> Excellent)	0 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease	9 Participants	10 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease: By 3 Categories (Excellent --> Poor)	0 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease: By 2 Categories	0 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease: By 2 Categories (Excellent -> Fair)	0 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease: By 2 Categories (Good -> Poor)	0 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease: By 1 Category	9 Participants	10 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease: By 1 Category (Excellent -> Good)	2 Participants	0 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease: By 1 Category (Good -> Fair)	5 Participants	7 Participants
Change From Baseline in Global Rating of Health (GRH) at Day 84 for the LAI Arm Compared to the Placebo Arm Decrease: By 1 Category (Fair -> Poor)	2 Participants	3 Participants

SECONDARY outcome

Timeframe: 84 days double-blind phase

Population: mITT

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.

Outcome measures

Outcome measures
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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.
Number of Participants Requiring "Rescue" Anti-mycobacterial or Other "Rescue" Drugs During the 84-day Double-blind Phase	21 participants	11 participants

SECONDARY outcome

Timeframe: 84 days double-blind phase

Population: mITT

Outcome measures

Outcome measures
Measure	LAI 590 mg QD n=44 Participants 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 n=45 Participants 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.
Number of Subject for "Rescue" Anti-mycobacterial or Other "Rescue" Drugs During the 84-day Double-blind Phase Number of subjects with the event	21 participants	11 participants
Number of Subject for "Rescue" Anti-mycobacterial or Other "Rescue" Drugs During the 84-day Double-blind Phase Number censored	23 participants	34 participants

Adverse Events

LAI 590 mg QD - Double Blind

Serious events: 8 serious events

Other events: 41 other events

Deaths: 1 deaths

Placebo - Double Blind

Serious events: 4 serious events

Other events: 39 other events

Deaths: 0 deaths

LAI 590 mg QD - Open Label

Serious events: 5 serious events

Other events: 31 other events

Deaths: 1 deaths

Placebo - Open Label

Serious events: 5 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Kevin Mange (Senior VP, Clinical Development)

Insmed Incorporated

Phone: 908-947-2651

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	LAI 590 mg QD - Double Blind n=44 participants at risk 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 - Double Blind n=45 participants at risk 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 - Open Label n=35 participants at risk 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 - Open Label n=43 participants at risk 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.
Infections and infestations Infective exacerbation of bronchiectasis	4.5% 2/44 • Number of events 2 • 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..	2.2% 1/45 • Number of events 1 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Infections and infestations Pneumonia	2.3% 1/44 • Number of events 1 • 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..	4.4% 2/45 • Number of events 2 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Infections and infestations Gastroenteritis viral	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Respiratory, thoracic and mediastinal disorders Eosinophilic pneumonia	0.00% 0/44 • 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..	2.2% 1/45 • Number of events 1 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Respiratory, thoracic and mediastinal disorders Haemoptysis	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Respiratory, thoracic and mediastinal disorders Respiratory disorder	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Injury, poisoning and procedural complications Femur fracture	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Injury, poisoning and procedural complications Humerus fracture	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Cardiac disorders Supraventricular tachycardia	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	0.00% 0/35 • 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..	2.3% 1/43 • Number of events 1 • 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..
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/44 • 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..	2.2% 1/45 • Number of events 1 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Metabolism and nutrition disorders Dehydration	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	0.00% 0/35 • 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..	0.00% 0/43 • 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..
Infections and infestations Infective pulmonary exacerbation of cystic fibrosis	2.3% 1/44 • Number of events 1 • 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..	0.00% 0/45 • 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..	5.7% 2/35 • Number of events 2 • 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..	7.0% 3/43 • Number of events 3 • 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..
Infections and infestations Urinary Tract Infection	0.00% 0/44 • 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..	0.00% 0/45 • 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..	2.9% 1/35 • Number of events 1 • 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..	0.00% 0/43 • 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..
Infections and infestations Urosepsis	0.00% 0/44 • 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..	0.00% 0/45 • 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..	2.9% 1/35 • Number of events 1 • 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..	0.00% 0/43 • 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..
Cardiac disorders Acute coronary syndrome	0.00% 0/44 • 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..	0.00% 0/45 • 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..	2.9% 1/35 • Number of events 1 • 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..	0.00% 0/43 • 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..
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/44 • 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..	0.00% 0/45 • 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..	2.9% 1/35 • Number of events 1 • 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..	2.3% 1/43 • Number of events 1 • 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..
Ear and labyrinth disorders Vertigo	0.00% 0/44 • 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..	0.00% 0/45 • 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..	2.9% 1/35 • Number of events 1 • 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..	0.00% 0/43 • 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..
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/44 • 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..	0.00% 0/45 • 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..	2.9% 1/35 • Number of events 1 • 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..	0.00% 0/43 • 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..
General disorders Multi-organ failure	0.00% 0/44 • 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..	0.00% 0/45 • 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..	2.9% 1/35 • Number of events 1 • 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..	0.00% 0/43 • 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..
Vascular disorders Deep Vein Thrombosis	0.00% 0/44 • 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..	0.00% 0/45 • 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..	2.9% 1/35 • Number of events 1 • 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..	0.00% 0/43 • 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..