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

Zambon SpA333 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

333

Conditions

Respiratory Tract Diseases Abnormal Mucus Secretions

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (32)

Wuxi Peoples' Hospital affiliated to Nanjing Medical University

Wuxi, No. 299, Qing Yang Rd., Wuxi City, Jiangsu, 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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: From Baseline upto Day 7

Secondary Outcomes

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

Time frame: From Baseline to Day 3

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.

Time frame: From Baseline to Day 3

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.

Time frame: From Baseline upto Day 3 and Day 7

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.

Time frame: From Baseline upto Day 3 and Day 7

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.

Time frame: From Baseline upto Day 3 and Day 7

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.

Time frame: From baseline upto Day 7

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

Time frame: From Baseline upto Day 7

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.

Time frame: From Baseline upto Day 3 and Day 7

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.

Time frame: From Baseline upto Day 3 and Day 7

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.

Time frame: From Baseline upto Day 3 and Day 7

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.

Time frame: From Baseline upto Day 3 and Day 7

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.

Time frame: From Baseline upto Day 3 and Day 7