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

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

Sponsors

Lead sponsor: Zambon SpA

Source Zambon SpA
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.

Overall Status Recruiting
Start Date June 25, 2019
Completion Date April 24, 2021
Primary Completion Date April 24, 2021
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Change from baseline to end of 1-week treatment of mean sputum viscosity score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to end of 1-week treatment of mean sputum viscosity score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to end of 1-week treatment of mean sputum viscosity score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to end of 1-week treatment of mean expectoration difficulty score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to end of 1-week treatment of mean expectoration difficulty score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to end of 1-week treatment of mean expectoration difficulty score of NAC and placebo From baseline upto 1-week treatment period
Secondary Outcome
Measure Time Frame
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 in mean expectoration difficulty score of NAC and placebo From baseline to Day 3
Change from baseline to day 3 and to the end of the 1-week treatment period in individual score of mean sputum viscosity score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in individual score of mean expectoration difficulty score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in individual score of mean sputum color score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in individual score of mean cough severity score of NAC and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period of mean sputum volume of NAC and placebo From baseline upto 1-week treatment period
Change from baseline in mean sputum viscosity score of NAC and ambroxol From baseline upto 1-week treatment period
Change from baseline in mean expectoration difficulty score of NAC and ambroxol From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in mean sputum viscosity score of ambroxol and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in individual score of mean sputum viscosity score of ambroxol and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in mean expectoration difficulty score of ambroxol and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in individual score of mean expectoration difficulty score of ambroxol and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in mean sputum color score of ambroxol and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in mean cough severity score of ambroxol and placebo From baseline upto 1-week treatment period
Change from baseline to day 3 and to the end of the 1-week treatment period in mean sputum volume of ambroxol and placebo From baseline upto 1-week treatment period
Enrollment 333
Condition
Intervention

Intervention type: Drug

Intervention name: N-acetylcysteine (NAC) 600 mg

Description: NAC will be administered twice a day, morning and evening, during treatment period.

Arm group label: Active test treatment-NAC

Other name: Fluimucil®

Intervention type: Drug

Intervention name: Ambroxol hydrochloride 30 mg

Description: Ambroxol hydrochloride will be administered twice a day, morning and evening, during treatment period.

Arm group label: Active control treatment-Ambroxol hydrochloride

Intervention type: Other

Intervention name: placebo

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

Arm group label: Placebo

Eligibility

Criteria:

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 ALT and/or AST 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Contact

Last name: Valentina Vaja

Phone: +39 02 665241

Email: [email protected]

Location
facility status contact
Wuxi Peoples' Hospital affiliated to Nanjing Medical University Recruiting Yinying Zhao
Inner Mongolia Baogang Hospital Recruiting Yang杨 Jingping敬平
Beijing Hospital Recruiting Xu Xiaomao
Beijing Tongren Hospital Not yet recruiting Liu 刘 Xiaofang 晓芳
China-Japan Friendship Hospital Not yet recruiting Yang 杨 Ting 汀
Peking University Shougang Hospital Recruiting Xiang 向 PingChao 平超
Jilin Province People's Hospital Recruiting AN 安 Dongshan 东善
Chengdu Fifth People's Hospital Not yet recruiting Chen 陈 Mei 梅
West China Hospital, Sichuan University Not yet recruiting Liang 梁 Zong-An 宗安
The First Affiliated Hospital of Chongqing Medical Universit Not yet recruiting Guo 郭 Shuliang 述良
People's Hospital of Deyang City Recruiting Chen 陈 Xuebing 学兵
People's Hospital of Inner Mongolia Autonomous Region Recruiting Xu徐 Maoye毛冶
The First Hospital of Jilin University Not yet recruiting Hua 华 Shucheng 树成
Jinhua city central hospital/Jinhua hospital ,School of Medicine,Zhejiang UNIVERSITY Not yet recruiting Chen Hui
The Second Affiliated Hospital of Nanchang University Not yet recruiting Yan 颜 Chunsong 春松
Nanjing First Hospital Recruiting Gu谷 Wei伟
Zhongda Hospital, Southeast University - Pulmonology Not yet recruiting Zhu 朱 Xiaoli 晓莉
Jiangxi Pingxiang People's Hospital Recruiting Dong Limin
Qingdao Municipal Hospital Not yet recruiting Han 韩 Wei 伟
Minhang District Central Hospital Not yet recruiting Yan 颜 Zhi Jun 志军
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine Recruiting Qu 瞿 Jieming 介明
Shanghai General Hospital Not yet recruiting Zhang 张 Min 旻
Shanghai Pulmonary Hospital Recruiting Xu 徐 Jinfu 金富
Suining Central Hospital Recruiting He 何 Zhengguang 正光
First Hospital of Shanxi Medical University Recruiting Zhang 张 Xinri 新日
Tongji Hospital, Tongji Medical College of Huazhong University Science and Technology Recruiting Xiong 熊 Shengdao 盛道
Wuxi Peoples' Hospital Not yet recruiting Zhao赵 Yinying寅滢
Yangzhou First People's Hospital Recruiting Wu Feng
General Hospital of Ningxia Medical University Recruiting Zhang 张 Jin 锦
Affiliated Hospital of Guangdong Medical University - Respiration Recruiting Li 黎 Dong-Ming 东明
Zigong First People's Hospital Recruiting Deng 邓 Zhiping 治平
Location Countries

China

Verification Date

May 2020

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 3
Arm Group

Arm group label: Active test treatment-NAC

Arm group type: Experimental

Description: NAC 600mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.

Arm group label: Active control treatment-Ambroxol hydrochloride

Arm group type: Active Comparator

Description: Ambroxol hydrochloride 30 mg will be administered by slow intravenous infusion twice daily for the 1-week treatment period.

Arm group label: Placebo

Arm group type: Placebo Comparator

Description: Placebo will be administered by slow intravenous infusion twice daily for the 1-week treatment period.

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: There will be 3 treatment groups of NAC, ambroxol and placebo. A total of 333 patients will be randomized to NAC or ambroxol or placebo in a 1:1:1 ratio. Approximately 111 patients will be randomized in each treatment group.

Primary purpose: Treatment

Masking: Double (Participant, Outcomes Assessor)

Masking description: Both rater and patient will be blinded.

Source: ClinicalTrials.gov