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
Overview
- Phase
- Phase 3
- Intervention
- N-acetylcysteine (NAC) 600 mg
- Conditions
- Respiratory Tract Diseases
- Sponsor
- Zambon SpA
- Enrollment
- 333
- Locations
- 31
- Primary Endpoint
- Change From Baseline to Day 7 of Mean Sputum Viscosity Score of NAC and Placebo
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Chinese ethnicity and/or Chinese
- •Signed the informed consent form before any study-related procedure
- •Sputum viscosity score ≥ 2 at randomization visit
- •Expectoration difficulty score ≥ 2 at randomization visit
- •Willingness and ability to comply with study procedures
Exclusion Criteria
- •Intolerance or contra-indication to treatment with NAC or ambroxol or allergy to any component of the study treatments
- •(For female patients) ongoing pregnancy or lactation, or childbearing potential but unwillingness to adopt abstinence or contraception measures during the study
- •Intake of an investigational drug within 1 month before the screening visit
- •Use of expectorants or drugs with expectorant effect within 2 days before randomization visit
- •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
- •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
- •Serum alanine aminotransferase and/or aspartate transaminase more than 3 times above the upper limit of normal at screening visit
- •Serum creatinine more than 3 times above the upper limit of normal at screening visit
- •Addiction to alcohol or drugs
- •Mental illness, or other reasons for non-cooperation in the investigator's opinion
Arms & Interventions
Active test treatment-NAC
NAC 600mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.
Intervention: N-acetylcysteine (NAC) 600 mg
Active control treatment-Ambroxol hydrochloride
Ambroxol hydrochloride 30 mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.
Intervention: Ambroxol hydrochloride 30 mg
Placebo
Placebo will be administered by slow intravenous infusion twice daily for the 1-week treatment period.
Intervention: placebo
Outcomes
Primary Outcomes
Change From Baseline to Day 7 of Mean Sputum Viscosity Score of NAC and Placebo
Time Frame: From baseline upto Day 7
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.
Change From Baseline to Day 7 Treatment of Mean Expectoration Difficulty Score of NAC and Placebo
Time Frame: From Baseline upto Day 7
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.
Secondary Outcomes
- Change From Baseline to Day 3 in Mean Expectoration Difficulty Score of NAC and Placebo(From Baseline to Day 3)
- Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of NAC and Placebo(From Baseline upto Day 3 and Day 7)
- Change From Baseline to Day 7 in Mean Sputum Viscosity Score of NAC and Ambroxol Hydrochloride(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(From Baseline upto Day 3 and Day 7)
- Change From Baseline to Day 3 in Mean Sputum Viscosity Score of NAC and Placebo(From Baseline to Day 3)
- Change From Baseline to Day 3 and to Day 7 in Mean Cough Severity Score of NAC and Placebo(From Baseline upto Day 3 and Day 7)
- Change From Baseline to Day 7 in Mean Expectoration Difficulty Score of NAC and Ambroxol Hydrochloride(From Baseline upto Day 7)
- Change From Baseline to Day 3 and to Day 7 in Mean Sputum Color Score of Ambroxol Hydrochloride and Placebo(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(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(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(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(From Baseline upto Day 3 and Day 7)