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

Respiratory Tract Diseases Clinical Trial

Official title:

A Phase III, Multi-centre, Randomized, Rater- and Patient-blind, Placebo- and Active-controlled, Parallel Group Clinical Trial to Compare the Efficacy and Safety of 1-week Treatment of Intravenous N-acetylcysteine (NAC) 600 mg Twice Daily (Active Test Treatment), Ambroxol Hydrochloride 30 mg Twice Daily (Active Control Treatment) and Placebo as Expectorant Therapies in Adult Chinese Patients With Respiratory Tract Diseases and Abnormal Mucus Secretions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03843541
• Other study ID #: Z7244L01
• Status: Completed
• Phase: Phase 3
• Start date: June 25, 2019
• Est. completion date: February 5, 2021

Study information

• Verified date: April 2022
• Source: Zambon SpA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 3, multicenter, randomized, rater- and patient-blind, placebo- and active-controlled, 3-arm parallel group clinical trial. Patients will be randomized to N-acetylcysteine (NAC) or ambroxol or placebo in a 1:1:1 ratio. A total of approximately 333 patients in China will be randomized. The total study duration will be approximately 8 months including the enrolment period of approximately 7 months and the patient participation duration of 1 month or 4 weeks. Each patient will undergo a screening period of up to 1 week, a 1-week treatment period and a 2-week follow-up period. This study will be conducted in approximately 15-25 sites in China.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 333
• Est. completion date: February 5, 2021
• Est. primary completion date: January 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female adult (=18 years old) hospitalized patients with respiratory tract diseases and abnormal mucus secretions such as: acute bronchitis, chronic bronchitis and exacerbations, emphysema, mucoviscidosis and bronchiectasis.

2. Chinese ethnicity and/or Chinese

3. Signed the informed consent form before any study-related procedure

4. Sputum viscosity score = 2 at randomization visit

5. Expectoration difficulty score = 2 at randomization visit

6. Willingness and ability to comply with study procedures

Exclusion Criteria:

1. Intolerance or contra-indication to treatment with NAC or ambroxol or allergy to any component of the study treatments

2. (For female patients) ongoing pregnancy or lactation, or childbearing potential but unwillingness to adopt abstinence or contraception measures during the study

3. Intake of an investigational drug within 1 month before the screening visit

4. Use of expectorants or drugs with expectorant effect within 2 days before randomization visit

5. Diagnosis of active tuberculosis, lung cancer, pulmonary fibrosis, acute pulmonary thromboembolism or any other respiratory condition that might, in the opinion of the investigator, compromise the safety of the patient or affect the interpretation of the results

6. Medical history of and/or illness (including laboratory abnormality) and/or treatment that in the investigator's opinion may interfere with the patient's safety, compliance, or study evaluations

7. Serum alanine aminotransferase and/or aspartate transaminase more than 3 times above the upper limit of normal at screening visit

8. Serum creatinine more than 3 times above the upper limit of normal at screening visit

9. Addiction to alcohol or drugs

10. Mental illness, or other reasons for non-cooperation in the investigator's opinion

Related Conditions & MeSH terms

• Abnormal Mucus Secretions
• Respiratory Tract Diseases

Intervention

Drug:
• N-acetylcysteine (NAC) 600 mg
NAC will be administered twice a day, morning and evening, during treatment period.
• Ambroxol hydrochloride 30 mg
Ambroxol hydrochloride will be administered twice a day, morning and evening, during treatment period.

Other:
• placebo
Placebo will be administered twice a day, morning and evening, during treatment period.

Locations

Country	Name	City	State
China	Inner Mongolia Baogang Hospital	Baotou
China	Beijing Hospital	Beijing
China	Beijing Tongren Hospital	Beijing
China	China-Japan Friendship Hospital	Beijing
China	Peking University Shougang Hospital	Beijing
China	Jilin Province People's Hospital	Changchun
China	The First Bethune Hospital of Jilin University	Changchun
China	Chengdu Fifth People's Hospital	Chengdu
China	West China Hospital, Sichuan University	Chengdu
China	The First Affiliated Hospital of Chongqing Medical University	Chongqing
China	Deyang People's Hospital	Deyang
China	Inner Mongolia People's Hospital	Hohhot
China	Jinhua city central hospital/Jinhua hospital ,School of Medicine,Zhejiang UNIVERSITY	Jinhua
China	Nanchang University-The Second Affiliated Hospital	Nanchang
China	Nanjing First Hospital	Nanjing
China	Zhongda Hospital, Southeast University - Pulmonology	Nanjing
China	Jiangxi Pingxiang People's Hospital	Pingxiang
China	Qingdao Municipal Hospital	Qingdao
China	Minhang District Central Hospital	Shanghai
China	Ruijin Hospital, Shanghai Jiao Tong University School of Medicine	Shanghai
China	Shanghai General Hospital	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai
China	Suining Central Hospital	SuiNing
China	First Hospital of Shanxi Medical University	Taiyuan
China	The First Hospital of Shanxi Medical University	Taiyuan
China	Tongji Hospital, Tongji Medical College of Huazhong University Science and Technology	Wuhan
China	Wuxi Peoples' Hospital affiliated to Nanjing Medical University	Wuxi
China	Wuxi Peoples' Hospital affiliated to Nanjing Medical University	Wuxi	No. 299, Qing Yang Rd., Wuxi City, Jiangsu
China	Yangzhou First People's Hospital	Yangzhou
China	General Hospital of Ningxia Medical University	Yinchuan
China	Affiliated Hospital of Guangdong Medical University - Respiration	Zhanjiang
China	The First People's Hospital of Zigong	Zigong

Sponsors (1)

Lead Sponsor	Collaborator
Zambon SpA

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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]
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.	From baseline upto Day 7
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.	From Baseline upto Day 7
Secondary	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.	From Baseline to Day 3
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.	From Baseline to Day 3
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.	From Baseline upto Day 3 and Day 7
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.	From Baseline upto Day 3 and Day 7
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.	From Baseline upto Day 3 and Day 7
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.	From baseline upto Day 7
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	From Baseline upto Day 7
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.	From Baseline upto Day 3 and Day 7
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.	From Baseline upto Day 3 and Day 7
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.	From Baseline upto Day 3 and Day 7
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.	From Baseline upto Day 3 and Day 7
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.	From Baseline upto Day 3 and Day 7