Trial Outcomes & Findings for Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium. (NCT NCT03460704)

Last Updated: 2023-12-29

Results Overview

The primary efficacy assessment for an individual subject was the frequency of pulmonary exacerbations (exacerbation rate). A pulmonary exacerbation was defined as the presence concurrently of at least three of the following eight symptoms/signs for at least 24 hours: * increased cough; * increased sputum volume and/or consistency; * increased sputum purulence; * new or increased haemoptysis; * increased wheezing; * increased dyspnoea; * increased fatigue/malaise and * episodes of fever (temperature ≥38°C). AND It was clinically determined that the subject required and was prescribed systemic antibiotic therapy. AND The episode of exacerbation lasted for at least 24 hours. The overall episode of exacerbation needs to last at least 24 hours, but individual symptoms/signs can last less than 24 hours (e.g, a temperature)

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

287 participants

Primary outcome timeframe

12 months

Results posted on

2023-12-29

Participant Flow

Recruitment was halted with 287 subjects randomised.

Participant milestones

Participant milestones
Measure	CMS (Colistimethate Sodium) Inhaled colistimethate sodium twice daily. The active pharmaceutical ingredient consisting of pure CMS one million international units (MIU) / 80 mg of CMS / 33 mg colistin base activity (CBA) was provided as a powder for nebuliser solution in 10R Internation Organization for Standardization (ISO) glass vials. CMS: 1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d. dosing). The 1 MIU/ml CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (11 mg CBA) from the device. The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d. (morning and evening) over aperiod of 12 month. At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g. salbutamol/albuterol), supplied by the Sponsor, could be taken to improve tolerability.	Placebo Saline solution inhaled twice daily, provided and administered at the same way of the IMP. Placebo: 1 mL saline solution 0.45%. The placebo was made up of identical empty glass vials to which the same saline solution diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to mantain the blind.
Overall Study NOT COMPLETED	58	46
Overall Study STARTED	152	135
Overall Study Modified Intention to Treat Population - (mITT)	152	135
Overall Study Safety Population - (SAF)	152	135
Overall Study Per-Protocol Population - (PP)	112	98
Overall Study COMPLETED	94	89

Reasons for withdrawal

Reasons for withdrawal
Measure	CMS (Colistimethate Sodium) Inhaled colistimethate sodium twice daily. The active pharmaceutical ingredient consisting of pure CMS one million international units (MIU) / 80 mg of CMS / 33 mg colistin base activity (CBA) was provided as a powder for nebuliser solution in 10R Internation Organization for Standardization (ISO) glass vials. CMS: 1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d. dosing). The 1 MIU/ml CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (11 mg CBA) from the device. The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d. (morning and evening) over aperiod of 12 month. At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g. salbutamol/albuterol), supplied by the Sponsor, could be taken to improve tolerability.	Placebo Saline solution inhaled twice daily, provided and administered at the same way of the IMP. Placebo: 1 mL saline solution 0.45%. The placebo was made up of identical empty glass vials to which the same saline solution diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to mantain the blind.
Overall Study Withdrawal by Subject	11	14
Overall Study Study terminated by the Sponsor	29	19
Overall Study Adverse Event	10	5
Overall Study Death	3	2
Overall Study Non-Compliance with Study Drug	3	0
Overall Study Protocol-Specified Withdrawal Criterion Met	0	5
Overall Study Other	2	1

Baseline Characteristics

Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CMS (Colistimethate Sodium) n=152 Participants Inhaled colistimethate sodium twice daily. The active pharmaceutical ingredient consisting of pure CMS one million international units (MIU) / 80 mg of CMS / 33 mg colistin base activity (CBA) was provided as a powder for nebuliser solution in 10R Internation Organization for Standardization (ISO) glass vials. CMS: 1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d. dosing). The 1 MIU/ml CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (11 mg CBA) from the device. The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d. (morning and evening) over aperiod of 12 month. At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g. salbutamol/albuterol), supplied by the Sponsor, could be taken to improve tolerability.	Placebo n=135 Participants Saline solution inhaled twice daily, provided and administered at the same way of the IMP. Placebo: 1 mL saline solution 0.45%. The placebo was made up of identical empty glass vials to which the same saline solution diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to mantain the blind.	Total n=287 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	85 Participants n=5 Participants	73 Participants n=7 Participants	158 Participants n=5 Participants
Age, Categorical >=65 years	67 Participants n=5 Participants	62 Participants n=7 Participants	129 Participants n=5 Participants
Age, Continuous	59.9 years STANDARD_DEVIATION 15.19 • n=5 Participants	59.6 years STANDARD_DEVIATION 14.73 • n=7 Participants	59.7 years STANDARD_DEVIATION 14.95 • n=5 Participants
Sex: Female, Male Female	104 Participants n=5 Participants	94 Participants n=7 Participants	198 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	41 Participants n=7 Participants	89 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	146 Participants n=5 Participants	130 Participants n=7 Participants	276 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Greece	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment New Zealand	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment Canada	9 participants n=5 Participants	10 participants n=7 Participants	19 participants n=5 Participants
Region of Enrollment Argentina	56 participants n=5 Participants	52 participants n=7 Participants	108 participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants	20 participants n=7 Participants	50 participants n=5 Participants
Region of Enrollment Poland	22 participants n=5 Participants	26 participants n=7 Participants	48 participants n=5 Participants
Region of Enrollment Italy	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Israel	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Australia	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment France	18 participants n=5 Participants	12 participants n=7 Participants	30 participants n=5 Participants
Region of Enrollment Portugal	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Germany	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: The modified Intention-To-Treat (mITT) Population is the Full Analysis Set and comprised all subjects who provided informed consent, were randomised and received at least 1 dose or partial dose of the IMP.

Outcome measures

Outcome measures
Measure	CMS (Colistimethate Sodium) n=152 Participants Inhaled colistimethate sodium twice daily. The active pharmaceutical ingredient consisting of pure CMS one million international units (MIU) / 80 mg of CMS / 33 mg colistin base activity (CBA) was provided as a powder for nebuliser solution in 10R Internation Organization for Standardization (ISO) glass vials. CMS: 1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d. dosing). The 1 MIU/ml CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (11 mg CBA) from the device. The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d. (morning and evening) over aperiod of 12 month. At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g. salbutamol/albuterol), supplied by the Sponsor, could be taken to improve tolerability.	Placebo n=135 Participants Saline solution inhaled twice daily, provided and administered at the same way of the IMP. Placebo: 1 mL saline solution 0.45%. The placebo was made up of identical empty glass vials to which the same saline solution diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to mantain the blind.
Mean Annual Non-cystic Fibrosis Bronchiectasis (NCFB) Pulmonary Exacerbation Rate	0.889 Number of Pulmonary Exacerbations Interval 0.722 to 1.093	0.885 Number of Pulmonary Exacerbations Interval 0.71 to 1.103

Adverse Events

CMS (Colistimethate Sodium) (SAF)

Serious events: 27 serious events

Other events: 123 other events

Deaths: 3 deaths

Placebo (SAF)

Serious events: 17 serious events

Other events: 104 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Michela Meroni - Clinical Trial Manager

Zambon S.p.A.

Phone: +39 02 665241

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	CMS (Colistimethate Sodium) (SAF) n=152 participants at risk Inhaled colistimethate sodium twice daily. The active pharmaceutical ingredient consisting of pure CMS one million international units (MIU) / 80 mg of CMS / 33 mg colistin base activity (CBA) was provided as a powder for nebuliser solution in 10R Internation Organization for Standardization (ISO) glass vials. CMS: 1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d. dosing). The 1 MIU/ml CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (11 mg CBA) from the device. The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d. (morning and evening) over aperiod of 12 month. At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g. salbutamol/albuterol), supplied by the Sponsor, could be taken to improve tolerability.	Placebo (SAF) n=135 participants at risk Saline solution inhaled twice daily, provided and administered at the same way of the IMP. Placebo: 1 mL saline solution 0.45%. The placebo was made up of identical empty glass vials to which the same saline solution diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to mantain the blind.
Infections and infestations Infective exacerbation of bronchiectasis	7.9% 12/152 • Number of events 12 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	7.4% 10/135 • Number of events 11 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations COVID-19	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Brain abscess	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations COVID-19 pneumonia	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Pneumonia	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Pseudomonas infection	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Respiratory syncytial virus infection	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Asthma	1.3% 2/152 • Number of events 2 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Haemoptysis	1.3% 2/152 • Number of events 2 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Bronchial disorder	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Injury, poisoning and procedural complications Forearm fracture	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Injury, poisoning and procedural complications Head injury	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Injury, poisoning and procedural complications Spinal compression fracture	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Cardiac disorders Adams-Stokes syndrome	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Cardiac disorders Cardiac failure	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Cardiac disorders Cardiac failure congestive	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Cardiac disorders Sinus arrest	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Cardiac disorders Sinus node dysfunction	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Constipation	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Diarrhoea	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Ileus	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Intestinal perforation	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
General disorders Death	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial cancer	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Peritoneal neoplasm	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Nervous system disorders Haemorrhagic stroke	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.

Other adverse events
Measure	CMS (Colistimethate Sodium) (SAF) n=152 participants at risk Inhaled colistimethate sodium twice daily. The active pharmaceutical ingredient consisting of pure CMS one million international units (MIU) / 80 mg of CMS / 33 mg colistin base activity (CBA) was provided as a powder for nebuliser solution in 10R Internation Organization for Standardization (ISO) glass vials. CMS: 1 MIU equivalent to 80 mg colistimethate sodium diluted in 1 mL saline solution 0.45%. Investigational Medicinal Product (IMP) glass vials were shrink wrapped in opaque white plastic and provided in boxes of 30 vials (two weeks of b.i.d. dosing). The 1 MIU/ml CMS/0.45% saline solution was transferred from the glass vial into a specific nebuliser system fitted with a 0.3 mL medication chamber, for administration by inhalation. This delivered a nominal dose of 0.3 MIU/24 mg CMS (11 mg CBA) from the device. The first dose of the IMP was administered at the site under the supervision of the site staff and subjects were instructed how to prepare and self-administer the IMP at home via a specific nebuliser system, b.i.d. (morning and evening) over aperiod of 12 month. At least 10 minutes (min) before each administration, an inhaled short-acting bronchodilator (e.g. salbutamol/albuterol), supplied by the Sponsor, could be taken to improve tolerability.	Placebo (SAF) n=135 participants at risk Saline solution inhaled twice daily, provided and administered at the same way of the IMP. Placebo: 1 mL saline solution 0.45%. The placebo was made up of identical empty glass vials to which the same saline solution diluent was added in exactly the same way as the reconstitution of the active treatment by injecting the diluent through the rubber stopper. The glass vials were shrink wrapped with opaque white plastic to mantain the blind.
Respiratory, thoracic and mediastinal disorders Asthma	3.3% 5/152 • Number of events 5 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Sputum increased	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	1.5% 2/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Constipation	2.6% 4/152 • Number of events 5 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Musculoskeletal and connective tissue disorders Arthralgia	1.3% 2/152 • Number of events 4 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 4 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Musculoskeletal and connective tissue disorders Muscoskeletal chest pain	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	1.5% 2/135 • Number of events 2 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Epistaxis	2.0% 3/152 • Number of events 4 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Dry mouth	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Dyspepsia	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.74% 1/135 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
General disorders Non-cardiac chest pain	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
General disorders Pyrexia	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Injury, poisoning and procedural complications Contusion	0.66% 1/152 • Number of events 1 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Nervous system disorders Syncope	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Injury, poisoning and procedural complications Exposure to contaminated device	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Investigations Weight decreased	0.00% 0/152 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Chronic sinusitis	2.0% 3/152 • Number of events 6 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	0.00% 0/135 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Infective exacerbation of bronchiectasis	45.4% 69/152 • Number of events 111 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	49.6% 67/135 • Number of events 103 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Cough	7.2% 11/152 • Number of events 15 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	6.7% 9/135 • Number of events 10 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Nervous system disorders Headache	4.6% 7/152 • Number of events 7 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	5.9% 8/135 • Number of events 8 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.9% 9/152 • Number of events 15 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	3.7% 5/135 • Number of events 8 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.6% 7/152 • Number of events 10 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	4.4% 6/135 • Number of events 7 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations COVID-19	5.3% 8/152 • Number of events 8 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	3.0% 4/135 • Number of events 4 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Sinusitis	3.9% 6/152 • Number of events 7 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	4.4% 6/135 • Number of events 10 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Diarrhoea	3.3% 5/152 • Number of events 8 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	4.4% 6/135 • Number of events 7 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Bronchospasm	4.6% 7/152 • Number of events 8 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 7 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Nasopharyngitis	1.3% 2/152 • Number of events 2 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	4.4% 6/135 • Number of events 6 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
General disorders Fatigue	3.9% 6/152 • Number of events 7 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	1.5% 2/135 • Number of events 2 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Vascular disorders Hypertension	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	3.0% 4/135 • Number of events 4 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Respiratory, thoracic and mediastinal disorders Wheezing	2.0% 3/152 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Influenza	2.6% 4/152 • Number of events 4 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	1.5% 2/135 • Number of events 2 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Infections and infestations Lower respiratory tract infection	2.0% 3/152 • Number of events 4 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	2.2% 3/135 • Number of events 3 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Gastrointestinal disorders Nausea	1.3% 2/152 • Number of events 2 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	3.0% 4/135 • Number of events 6 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.
Musculoskeletal and connective tissue disorders Back pain	1.3% 2/152 • Number of events 4 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.	3.0% 4/135 • Number of events 5 • All AEs occurring from Visit 2 (day 0 = first IMP administration) until the follow-up phone call (2 weeks +/- 3 days after the end of treatment = totally up to 54 weeks +/- 3 days from the study Day 0. An AE is "any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment". An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an IMP, whether or not considered related to the IMP.