A Clinical Trial to Compare the Efficacy and Safety of 1-... | NCT03843541

Label	Type	Description	Intervention Names
Active test treatment-NAC	Experimental	NAC 600mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.	Drug: N-acetylcysteine (NAC) 600 mg
Active control treatment-Ambroxol hydrochloride	Active Comparator	Ambroxol hydrochloride 30 mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.	Drug: Ambroxol hydrochloride 30 mg
Placebo	Placebo Comparator	Placebo will be administered by slow intravenous infusion twice daily for the 1-week treatment period.	Other: placebo

Name	Type	Description	Arm Group Labels	Other Names
N-acetylcysteine (NAC) 600 mg	Drug	NAC will be administered twice a day, morning and evening, during treatment period.	Active test treatment-NAC

Measure	Description	Time Frame
Change From Baseline to Day 7 of Mean Sputum Viscosity Score of NAC and Placebo	The superiority of slow intravenous infusion of NAC to placebo in terms of change from baseline in sputum viscosity score was demonstrated. Sputum viscosity was assessed by ordinal categorical 4-point scales [0 = Liquid (normal viscosity), 1= Fluid (mildly increased viscosity), 2 = Viscous (moderately increased viscosity), 3 = Sticky (severely increased viscosity)] with 0 = best and 3= worst.	From baseline upto Day 7
Change From Baseline to Day 7 Treatment of Mean Expectoration Difficulty Score of NAC and Placebo	The superiority of slow intravenous infusion of NAC 600 mg twice daily to placebo in terms of change from baseline in expectoration difficulty score was demonstrated. Expectoration difficulty was assessed by ordinal categorical 4-point scales [0 = No difficulty, 1 = Mild difficulty, 2 = Moderate difficulty, 3 = Marked difficulty] with 0 = best and 3 = worst.	From Baseline upto Day 7

Measure	Description	Time Frame
Change From Baseline to Day 3 in Mean Sputum Viscosity Score of NAC and Placebo	The superiority of slow intravenous infusion of NAC to placebo in terms of change from baseline in sputum viscosity score was demonstrated. Sputum viscosity was assessed by ordinal categorical 4-point scales [0 = Liquid (normal viscosity), 1= Fluid (mildly increased viscosity), 2 = Viscous (moderately increased viscosity), 3 = Sticky (severely increased viscosity)] with 0 = best and 3= worst.

Measure	Description	Time Frame
Number of Participants With Adverse Events	The safety and tolerability of intravenous NAC 600 mg twice daily was demonstrated.	From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]

Facility	Status	City	State	ZIP	Country	Contacts
Wuxi Peoples' Hospital affiliated to Nanjing Medical University		Wuxi	No. 299, Qing Yang Rd., Wuxi City, Jiangsu		China

ID	Title	Description
FG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg slow intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
FG001	Ambroxol Hydrochloride

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 19, 2018	Jan 19, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Day 7 of Mean Sputum Viscosity Score of NAC and Placebo

The superiority of slow intravenous infusion of NAC to placebo in terms of change from baseline in sputum viscosity score was demonstrated. Sputum viscosity was assessed by ordinal categorical 4-point scales [0 = Liquid (normal viscosity), 1= Fluid (mildly increased viscosity), 2 = Viscous (moderately increased viscosity), 3 = Sticky (severely increased viscosity)] with 0 = best and 3= worst.

mITT population - The Modified ITT (mITT) Population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From baseline upto Day 7

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants	OG000108 OG001110

Title

Denominators

Categories

Title	Measurements
	OG000-1.2± 0.74 OG001-1.0± 0.78

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	For the superiority comparisons of NAC vs. placebo, the Bonferroni correction was used.	Wilcoxon (Mann-Whitney)		<0.001		Mean Difference (Net)	-0.24	Standard Deviation	0.763	2-Sided								Superiority

Primary

Change From Baseline to Day 7 Treatment of Mean Expectoration Difficulty Score of NAC and Placebo

The superiority of slow intravenous infusion of NAC 600 mg twice daily to placebo in terms of change from baseline in expectoration difficulty score was demonstrated. Expectoration difficulty was assessed by ordinal categorical 4-point scales [0 = No difficulty, 1 = Mild difficulty, 2 = Moderate difficulty, 3 = Marked difficulty] with 0 = best and 3 = worst.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline upto Day 7

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 in Mean Sputum Viscosity Score of NAC and Placebo

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline to Day 3

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 in Mean Expectoration Difficulty Score of NAC and Placebo

The superiority of slow intravenous infusion of NAC to placebo in terms of change from baseline in expectoration difficulty score was demonstrated. Expectoration difficulty was assessed by ordinal categorical 4-point scales [0 = No difficulty, 1 = Mild difficulty, 2 = Moderate difficulty, 3 = Marked difficulty] with 0 = best and 3 = worst.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline to Day 3

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of NAC and Placebo

The superiority of the slow intravenous infusion of NAC to placebo in terms of change from baseline in sputum color score was demonstrated. Sputum color was assessed by means of ordinal categorical 4-point scales [0 = Mostly white, 1= Mostly pale yellow, 2 = Mostly dark yellow, 3 = Very dark yellow /green] with 0 = best and 3= worst.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline upto Day 3 and Day 7

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of NAC and Placebo

The superiority of the slow intravenous infusion of NAC to placebo in terms of change from baseline in cough score was demonstrated. Cough score was assessed by means of ordinal categorical 4-point scales [0 = No cough, 1= Sporadic and mild cough, 2 = Moderate cough, 3 = Severe Cough] with 0 = best and 3= worst.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline upto Day 3 and Day 7

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 and to Day 7 of Mean Sputum Volume of NAC and Placebo

The superiority of the slow intravenous infusion of NAC to placebo in terms of change from baseline in sputum volume was demonstrated. Patients collected 24-hour sputum (morning to same time of the following morning) in a graduated cup and volume was expressed as mL/24h.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

mL/24h

From Baseline upto Day 3 and Day 7

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 7 in Mean Sputum Viscosity Score of NAC and Ambroxol Hydrochloride

The non-inferiority of NAC versus ambroxol in terms of change from baseline to Day 7 of mean sputum viscosity score was demonstrated. Sputum viscosity was assessed by ordinal categorical 4-point scales [0 = Liquid (normal viscosity), 1= Fluid (mildly increased viscosity), 2 = Viscous (moderately increased viscosity), 3 = Sticky (severely increased viscosity)] with 0 = best and 3= worst.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From baseline upto Day 7

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 7 in Mean Expectoration Difficulty Score of NAC and Ambroxol Hydrochloride

The non-inferiority of NAC versus ambroxol in terms of change from baseline to Day 7 of mean expectoration difficulty score was demonstrated. Expectoration difficulty was assessed by ordinal categorical 4-point scales [0 = No difficulty, 1 = Mild difficulty, 2 = Moderate difficulty, 3 = Marked difficulty] with 0 = best and 3= worst

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline upto Day 7

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 and to Day 7 in Mean Sputum Viscosity Score of Ambroxol Hydrochloride and Placebo

The superiority of the slow intravenous infusion ambroxol hydrochloride to placebo in terms of change from baseline in sputum viscosity score was demonstrated. Sputum viscosity was assessed by ordinal categorical 4-point scales [0 = Liquid (normal viscosity), 1= Fluid (mildly increased viscosity), 2 = Viscous (moderately increased viscosity), 3 = Sticky (severely increased viscosity)] with 0 = best and 3= worst.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline upto Day 3 and Day 7

ID	Title	Description
OG000	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 and to Day 7 in Mean Expectoration Difficulty Score of Ambroxol Hydrochloride and Placebo

The superiority of the slow intravenous infusion of ambroxol hydrochloride to placebo in terms of change from baseline in expectoration difficulty score was demonstrated. Expectoration difficulty was assessed by ordinal categorical 4-point scales [0 = No difficulty, 1 = Mild difficulty, 2 = Moderate difficulty, 3 = Marked difficulty] with 0 = best and 3 = worst.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline upto Day 3 and Day 7

ID	Title	Description
OG000	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of Ambroxol Hydrochloride and Placebo

The superiority of slow intravenous infusion of ambroxol hydrochloride to placebo in terms of change from baseline in sputum color was demonstrated. Sputum color was assessed by means of ordinal categorical 4-point scales [0 = Mostly white, 1= Mostly pale yellow, 2 = Mostly dark yellow, 3 = Very dark yellow /green] with 0 = best and 3= worst.

mITT population - The Modified ITT (mITT) Population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline upto Day 3 and Day 7

ID	Title	Description
OG000	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of Ambroxol Hydrochloride and Placebo

The superiority of slow intravenous infusion of ambroxol hydrochloride to placebo in terms of change from baseline in cough score was demonstrated. Cough score was assessed by means of ordinal categorical 4-point scales [0 = No cough, 1= Sporadic and mild cough, 2 = Moderate cough, 3 = Severe Cough] with 0 = best and 3= worst.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

Score

From Baseline upto Day 3 and Day 7

ID	Title	Description
OG000	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Secondary

Change From Baseline to Day 3 and to Day 7 in Mean Sputum Volume of Ambroxol Hydrochloride and Placebo

The superiority of slow intravenous infusion of ambroxol hydrochloride to placebo in terms of change from baseline in mean sputum volume was demonstrated. Patients collected 24-hour sputum (morning to same time of the following morning) in a graduated cup and volume was expressed as mL/24h.

mITT population - The mITT population comprised all participants in the ITT population who received at least 1 dose or partial dose of the IMP.

Posted

Mean

Standard Deviation

mL/24h

From Baseline upto Day 3 and Day 7

ID	Title	Description
OG000	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
OG001	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Units	Counts
Participants

Other Pre-specified

Number of Participants With Adverse Events

The safety and tolerability of intravenous NAC 600 mg twice daily was demonstrated.

The safety population included all subjects who provided informed consent and received at least 1 dose or partial dose of the IMP. Subjects were analyzed according to the treatment they actually received.

Posted

Count of Participants

Participants

From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]

ID	Title	Description
OG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg slow intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
OG001	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
OG002	Placebo	Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Constipation	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0014 events4 affected110 at risk EG0022 events2 affected110 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0003 events3 affected108 at risk EG0010 events0 affected110 at risk EG0025 events4 affected110 at risk
Nausea	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0013 events3 affected110 at risk EG0022 events2 affected110 at risk
Chronic gastritis	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0004 events4 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0022 events2 affected110 at risk
Dry mouth	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0013 events3 affected110 at risk EG0020 events0 affected110 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0022 events2 affected110 at risk
Vomiting	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0022 events2 affected110 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0022 events2 affected110 at risk
Ascites	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Epigastric discomfort	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Gastritis	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Gastrointestinal disorder	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Gastrointestinal mucosal disorder	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Gastroptosis	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Gingival disorder	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Leukoplakia oral	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Mouth ulceration	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Rectal polyp	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Tongue dry	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG00013 events13 affected108 at risk EG0019 events9 affected110 at risk EG0029 events9 affected110 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0023 events3 affected110 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected110 at risk EG0022 events1 affected110 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Hypochloraemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0022 events2 affected110 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0022 events2 affected110 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Gout	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Pulmonary mass	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0014 events4 affected110 at risk EG0021 events1 affected110 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0012 events2 affected110 at risk EG0020 events0 affected110 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0003 events3 affected108 at risk EG0012 events2 affected110 at risk EG0020 events0 affected110 at risk
Pulmonary hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0012 events2 affected110 at risk EG0022 events2 affected110 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0013 events1 affected110 at risk EG0020 events0 affected110 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Bronchial hyperreactivity	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Hypoventilation	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Nasal septum deviation	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Oropharyngeal discomfort	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Paranasal cyst	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Pharyngeal disorder	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Pulmonary arterial hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Respiratory acidosis	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Tachypnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Pneumonia	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0004 events4 affected108 at risk EG0013 events3 affected110 at risk EG0023 events2 affected110 at risk
Sinusitis	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0013 events3 affected110 at risk EG0020 events0 affected110 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0012 events2 affected110 at risk EG0020 events0 affected110 at risk
Nasopharyngitis	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0022 events2 affected110 at risk
Asymptomatic bacteriuria	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Bronchopulmonary aspergillosis allergic	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Infective exacerbation of bronchiectasis	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Respiratory tract infection fungal	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Chronic sinusitis	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Infectious pleural effusion	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0022 events1 affected110 at risk
Influenza	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Kidney infection	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Lymph node tuberculosis	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Pharyngitis	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Urinary tract infection	Infections and infestations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Alanine aminotransferase increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0012 events2 affected110 at risk EG0021 events1 affected110 at risk
Blood potassium decreased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0012 events2 affected110 at risk EG0020 events0 affected110 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Blood pressure increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0022 events2 affected110 at risk
Electrocardiogram abnormal	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Platelet count increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Respiratory rate increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Urinary occult blood positive	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
White blood cell count decreased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Beta 2 microglobulin increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Blood glucose decreased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Blood pressure systolic decreased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Carbohydrate antigen 19-9 increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Carbon dioxide increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Carcinoembryonic antigen increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Electrocardiogram Q wave abnormal	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Electrocardiogram ST segment depression	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Electrocardiogram T wave abnormal	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Electrocardiogram T wave inversion	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Fibrin D dimer increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Heart rate increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
International normalised ratio increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Neutrophil count decreased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Neutrophil count increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Rheumatoid factor increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Transaminases increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Tumour marker increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
White blood cell count increased	Investigations	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Hepatic cyst	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0013 events3 affected110 at risk EG0024 events4 affected110 at risk
Hepatic steatosis	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0003 events3 affected108 at risk EG0012 events2 affected110 at risk EG0021 events1 affected110 at risk
Gallbladder polyp	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0012 events2 affected110 at risk EG0022 events2 affected110 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0012 events2 affected110 at risk EG0022 events2 affected110 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0022 events2 affected110 at risk
Liver disorder	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Biliary dilatation	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Gallbladder cholesterolosis	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Hepatic calcification	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Cardiac failure	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0003 events2 affected108 at risk EG0012 events2 affected110 at risk EG0022 events2 affected110 at risk
Supraventricular extrasystoles	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0012 events2 affected110 at risk EG0021 events1 affected110 at risk
Arrhythmia	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Atrial fibrillation	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Sinus tachycardia	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0022 events2 affected110 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Bundle branch block right	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Cardiomegaly	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Cor pulmonale	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Cor pulmonale chronic	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Coronary artery disease	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Left ventricular dysfunction	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Pericardial effusion	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Sinus bradycardia	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Sinus node dysfunction	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Tricuspid valve incompetence	Cardiac disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0004 events4 affected108 at risk EG0013 events3 affected110 at risk EG0023 events3 affected110 at risk
Renal cyst	Renal and urinary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0016 events6 affected110 at risk EG0023 events3 affected110 at risk
Glycosuria	Renal and urinary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Renal failure	Renal and urinary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0012 events2 affected110 at risk EG0020 events0 affected110 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Dizziness	Nervous system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0003 events3 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Headache	Nervous system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0003 events3 affected108 at risk EG0012 events2 affected110 at risk EG0020 events0 affected110 at risk
Carotid arteriosclerosis	Nervous system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Cerebral atrophy	Nervous system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Hypoxic-ischaemic encephalopathy	Nervous system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Poor quality sleep	Nervous system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Spinal meningeal cyst	Nervous system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Hypertension	Vascular disorders	MedDRA (23.1)	Non-systematic Assessment	EG0003 events2 affected108 at risk EG0011 events1 affected110 at risk EG0022 events2 affected110 at risk
Arteriosclerosis	Vascular disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Phlebitis	Vascular disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Aortic arteriosclerosis	Vascular disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Arterial stiffness	Vascular disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Ischaemia	Vascular disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Varicose vein	Vascular disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Chest discomfort	General disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Pyrexia	General disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events1 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Asthenia	General disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Face oedema	General disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Fatigue	General disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Non-cardiac chest pain	General disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Oedema peripheral	General disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Peripheral swelling	General disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0012 events2 affected110 at risk EG0024 events3 affected110 at risk
Calculus prostatic	Reproductive system and breast disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0013 events3 affected110 at risk EG0021 events1 affected110 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0022 events2 affected110 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Palmoplantar keratoderma	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Purpura	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Skin discomfort	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Thyroid mass	Endocrine disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0013 events3 affected110 at risk EG0022 events2 affected110 at risk
Goitre	Endocrine disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Secondary hypothyroidism	Endocrine disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0014 events4 affected110 at risk EG0020 events0 affected110 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0012 events2 affected110 at risk EG0020 events0 affected110 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Degenerative bone disease	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0002 events2 affected108 at risk EG0012 events2 affected110 at risk EG0020 events0 affected110 at risk
Coagulopathy	Blood and lymphatic system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Granulocytopenia	Blood and lymphatic system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Leukocytosis	Blood and lymphatic system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Adrenal adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Metastases to lymph nodes	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Renal hemangioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Age-related macular degeneration	Eye disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Cataract	Eye disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Corneal leukoma	Eye disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Dry eye	Eye disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Xerophthalmia	Eye disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Hypersensitivity	Immune system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0020 events0 affected110 at risk
Immunodeficiency	Immune system disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA (23.1)	Non-systematic Assessment	EG0001 events1 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk
Foreign body in respiratory tract	Injury, poisoning and procedural complications	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0020 events0 affected110 at risk
Insomnia	Psychiatric disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0011 events1 affected110 at risk EG0021 events1 affected110 at risk
Agitation	Psychiatric disorders	MedDRA (23.1)	Non-systematic Assessment	EG0000 events0 affected108 at risk EG0010 events0 affected110 at risk EG0021 events1 affected110 at risk

ID	Term
D012140	Respiratory Tract Diseases
D001991	Bronchitis
D003550	Cystic Fibrosis
D003371	Cough
D029424	Pulmonary Disease, Chronic Obstructive

ID	Term
D012141	Respiratory Tract Infections
D007239	Infections
D001982	Bronchial Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D010182	Pancreatic Diseases
D004066	Digestive System Diseases
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D007232	Infant, Newborn, Diseases
D012120	Respiration Disorders
D012818	Signs and Symptoms, Respiratory
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes

ID	Term
D003545	Cysteine
D000603	Amino Acids, Sulfur
D013457	Sulfur Compounds
D009930	Organic Chemicals
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D001964	Bromhexine
D000814	Aniline Compounds
D000588	Amines
D003514	Cyclohexylamines

ID	Title	Description
BG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.
BG001	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
BG002	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	N-Acetylcysteine	Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	1	108	2	108	67	108
EG001	Ambroxol Hydrochloride	Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	0	110	5	110	66	110
EG002	Placebo	Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	0	110	7	110	58	110