Trial Outcomes & Findings for A Clinical Trial to Compare the Efficacy and Safety of 1-week Treatment of Intravenous N-acetylcysteine (NAC) 600 mg Twice Daily, Ambroxol Hydrochloride 30 mg Twice Daily and Placebo as Expectorant Therapies in Adult Chinese Patients With Respiratory Tract Diseases and Abnormal Mucus Secretions (NCT NCT03843541)

Last Updated: 2025-09-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

333 participants

Primary outcome timeframe

From baseline upto Day 7

Results posted on

2025-09-05

Participant Flow

The study was conducted between 21-June-2019 and 5-February-2021 in 28 sites in China.

Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All procedures were performed as per the trial flow chart.

Participant milestones

Participant milestones
Measure	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.	Ambroxol Hydrochloride Participants received Ambroxol hydrochloride 30 mg slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Overall Study STARTED	111	111	111
Overall Study Modified ITT	108	110	110
Overall Study COMPLETED	96	95	97
Overall Study NOT COMPLETED	15	16	14

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	Ambroxol Hydrochloride Participants received Ambroxol hydrochloride 30 mg slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Overall Study Adverse Event	4	2	3
Overall Study Death	1	0	0
Overall Study Lack of adherence to study medication	0	0	1
Overall Study Physician Decision	1	2	2
Overall Study Study subject withdrawal by parent or guardian	1	0	0
Overall Study Withdrawal by Subject	6	9	7
Overall Study Administration of rescue mucolytic	0	0	1
Overall Study Reporting drug over temperature, patients plan to transfer to hospital, and discharge from hospital.	2	3	0

Baseline Characteristics

A Clinical Trial to Compare the Efficacy and Safety of 1-week Treatment of Intravenous N-acetylcysteine (NAC) 600 mg Twice Daily, Ambroxol Hydrochloride 30 mg Twice Daily and Placebo as Expectorant Therapies in Adult Chinese Patients With Respiratory Tract Diseases and Abnormal Mucus Secretions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Ambroxol Hydrochloride n=110 Participants Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Total n=328 Participants Total of all reporting groups
Age, Continuous	64.7 years STANDARD_DEVIATION 11.65 • n=5 Participants	64.7 years STANDARD_DEVIATION 12.76 • n=7 Participants	64.5 years STANDARD_DEVIATION 12.79 • n=5 Participants	64.6 years STANDARD_DEVIATION 12.38 • n=4 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	31 Participants n=7 Participants	32 Participants n=5 Participants	99 Participants n=4 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	79 Participants n=7 Participants	78 Participants n=5 Participants	229 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	108 Participants n=5 Participants	110 Participants n=7 Participants	110 Participants n=5 Participants	328 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: From baseline upto Day 7

Population: 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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 7 of Mean Sputum Viscosity Score of NAC and Placebo	-1.2 Score Standard Deviation 0.74	-1.0 Score Standard Deviation 0.78	—

PRIMARY outcome

Timeframe: From Baseline upto Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 7 Treatment of Mean Expectoration Difficulty Score of NAC and Placebo	-1.4 Score Standard Deviation 0.78	-1.1 Score Standard Deviation 0.78	—

SECONDARY outcome

Timeframe: From Baseline to Day 3

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

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 in Mean Sputum Viscosity Score of NAC and Placebo	-0.6 Score Standard Deviation 0.59	-0.6 Score Standard Deviation 0.64	—

SECONDARY outcome

Timeframe: From Baseline to Day 3

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 in Mean Expectoration Difficulty Score of NAC and Placebo	-0.8 Score Standard Deviation 0.61	-0.7 Score Standard Deviation 0.64	—

SECONDARY outcome

Timeframe: From Baseline upto Day 3 and Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of NAC and Placebo Change from baseline to Day 3	-0.5 Score Standard Deviation 0.72	-0.5 Score Standard Deviation 0.82	—
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of NAC and Placebo Change from baseline to Day 7	-0.8 Score Standard Deviation 0.89	-0.8 Score Standard Deviation 0.97	—

SECONDARY outcome

Timeframe: From Baseline upto Day 3 and Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of NAC and Placebo Change from baseline to Day 3	-0.4 Score Standard Deviation 0.55	-0.5 Score Standard Deviation 0.60	—
Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of NAC and Placebo Change from baseline to Day 7	-0.8 Score Standard Deviation 0.77	-0.6 Score Standard Deviation 0.72	—

SECONDARY outcome

Timeframe: From Baseline upto Day 3 and Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 and to Day 7 of Mean Sputum Volume of NAC and Placebo Change from baseline to Day 3	-1.601 mL/24h Standard Deviation 16.2611	-4.144 mL/24h Standard Deviation 12.2348	—
Change From Baseline to Day 3 and to Day 7 of Mean Sputum Volume of NAC and Placebo Change from baseline to Day 7	-9.405 mL/24h Standard Deviation 35.2191	-7.391 mL/24h Standard Deviation 15.9992	—

SECONDARY outcome

Timeframe: From baseline upto Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 7 in Mean Sputum Viscosity Score of NAC and Ambroxol Hydrochloride	-1.2 Score Standard Deviation 0.74	-1.2 Score Standard Deviation 0.78	—

SECONDARY outcome

Timeframe: From Baseline upto Day 7

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

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

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 7 in Mean Expectoration Difficulty Score of NAC and Ambroxol Hydrochloride	-1.4 Score Standard Deviation 0.78	-1.3 Score Standard Deviation 0.75	—

SECONDARY outcome

Timeframe: From Baseline upto Day 3 and Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=110 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Viscosity Score of Ambroxol Hydrochloride and Placebo Change from baseline to Day 3	-0.6 Score Standard Deviation 0.55	-0.6 Score Standard Deviation 0.64	—
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Viscosity Score of Ambroxol Hydrochloride and Placebo Change from baseline to Day 7	-1.2 Score Standard Deviation 0.78	-1.0 Score Standard Deviation 0.78	—

SECONDARY outcome

Timeframe: From Baseline upto Day 3 and Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=110 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 and to Day 7 in Mean Expectoration Difficulty Score of Ambroxol Hydrochloride and Placebo Change from baseline to Day 7	-1.3 Score Standard Deviation 0.75	-1.1 Score Standard Deviation 0.78	—
Change From Baseline to Day 3 and to Day 7 in Mean Expectoration Difficulty Score of Ambroxol Hydrochloride and Placebo Change from baseline to Day 3	-0.7 Score Standard Deviation 0.57	-0.7 Score Standard Deviation 0.64	—

SECONDARY outcome

Timeframe: From Baseline upto Day 3 and Day 7

Population: 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.

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=110 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of Ambroxol Hydrochloride and Placebo Change from baseline to Day 7	-0.9 Score Standard Deviation 0.99	-0.8 Score Standard Deviation 0.97	—
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of Ambroxol Hydrochloride and Placebo Change from baseline to Day 3	-0.5 Score Standard Deviation 0.77	-0.5 Score Standard Deviation 0.82	—

SECONDARY outcome

Timeframe: From Baseline upto Day 3 and Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=110 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of Ambroxol Hydrochloride and Placebo Change from baseline to Day 3	-0.4 Score Standard Deviation 0.52	-0.5 Score Standard Deviation 0.60	—
Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of Ambroxol Hydrochloride and Placebo Change from baseline to Day 7	-0.7 Score Standard Deviation 0.68	-0.6 Score Standard Deviation 0.72	—

SECONDARY outcome

Timeframe: From Baseline upto Day 3 and Day 7

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

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.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=110 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Volume of Ambroxol Hydrochloride and Placebo Change from baseline to Day 3	-4.53 mL/24h Standard Deviation 12.018	-4.14 mL/24h Standard Deviation 12.235	—
Change From Baseline to Day 3 and to Day 7 in Mean Sputum Volume of Ambroxol Hydrochloride and Placebo Change from baseline to Day 7	-9.73 mL/24h Standard Deviation 15.149	-7.39 mL/24h Standard Deviation 15.999	—

OTHER_PRE_SPECIFIED outcome

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

Population: 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.

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

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=108 Participants Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo n=110 Participants Participants received placebo slow intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Number of Participants With Adverse Events At least one AE	82 Participants	76 Participants	71 Participants
Number of Participants With Adverse Events At least one TESAE	2 Participants	5 Participants	7 Participants
Number of Participants With Adverse Events At least one TESAE leading to fatal outcome	1 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events At least one TESAE of COVID-19	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events At least one TEAE	67 Participants	66 Participants	58 Participants
Number of Participants With Adverse Events At least one IMP-related TEAE	11 Participants	11 Participants	0 Participants
Number of Participants With Adverse Events At least one TEAE leading to drug withdrawal	5 Participants	2 Participants	3 Participants
Number of Participants With Adverse Events At least one TEAE leading to drug interruption	0 Participants	0 Participants	1 Participants
Number of Participants With Adverse Events At least one TEAE leading to fatal outcome	1 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events At least one severe TEAE	5 Participants	4 Participants	7 Participants
Number of Participants With Adverse Events At least one TEAE of COVID-19	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events At least one SAE	2 Participants	5 Participants	7 Participants
Number of Participants With Adverse Events At least one TESAE leading to drug withdrawal	1 Participants	1 Participants	1 Participants
Number of Participants With Adverse Events At least one TESAE leading to drug interruption	0 Participants	0 Participants	1 Participants

Adverse Events

N-Acetylcysteine

Serious events: 2 serious events

Other events: 67 other events

Deaths: 1 deaths

Ambroxol Hydrochloride

Serious events: 5 serious events

Other events: 66 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	N-Acetylcysteine n=108 participants at risk Participants received N-Acetylcysteine (NAC) 600 mg intravenous (IV) infusion twice daily (BD - morning and evening) for the 1-week treatment period.	Ambroxol Hydrochloride n=110 participants at risk Participants received Ambroxol hydrochloride 30 mg intravenous infusion twice daily (morning and evening) for the 1-week treatment period.	Placebo n=110 participants at risk Participants received placebo intravenous infusion twice daily (morning and evening) for the 1-week treatment period.
Cardiac disorders Cardiac failure	0.93% 1/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small lung cancer	0.93% 1/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Immune system disorders Anti-neutrophil cytoplasmic antibody positive vasculitis	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Cardiac disorders Coronary artery disease	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Infections and infestations Bronchopulmonary aspergillosis allergic	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	1.8% 2/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Endocrine disorders Thyroid mass	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Congenital, familial and genetic disorders Congenital cerebrovascular anomaly	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/108 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.00% 0/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.	0.91% 1/110 • From screening to follow-up after the last administration of the investigational medicinal product (IMP) [assessed up to 19 months]. The Safety Population has been considered to report AEs. It comprised 328 subjects who provided informed consent and received at least 1 dose or partial dose of the IMP.

Other adverse events

Additional Information

Valentina Zanin

Zambon S.p.A.

Phone: +39026652441

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee This document contains confidential information of Zambon S.p.A. Do not copy or distribute without written permission from the sponsor.
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