Single Arm Post Marketing Study to Evaluate Safety and Efficacy of Ambronac Tablets in Adult Bronchitis Patients with Excess Mucus Production

Brief Summary: In bronchitis, bronchial tubes that carry air to the lungs get inflamed or infected. They produce a lot of slimy substance called mucus. To get rid of this excess mucus, usually the patient repeatedly coughs. Thus, persistent coughing is the main symptom of bronchitis. Other symptoms include low-grade fever, shortness of breath and wheezing. There are two types, acute and chronic bronchitis. Acute bronchitis is a transient inflammation of trachea and major bronchi. It is often as a result of exposure to irritants or infections. Usually, acute bronchitis is contagious.  Cigarette smoking is the main cause of chronic bronchitis. A person with chronic bronchitis suffers irreversible scarring of lungs which leads to difficulty in breathing and increased risks for infections. Chronic bronchitis is not contagious. Ambroxol is a mucus modifying drug that is widely used in treating the respiratory tract disorders including bronchitis. Ambroxol has been widely studied for clinical use to assess its effectiveness in respiratory diseases characterized by airway mucus hyper-secretion such as chronic obstructive pulmonary disease (COPD) and prevention of chronic bronchitis exacerbations Unlike other mucolytic agents, ambroxol also activates the surfactant system of the lung. A surfactant is believed to act as an anti-glue factor in the alveoli and bronchi and prevent secretions from sticking to the walls of the bronchial tree, thus facilitating mucus transport. Ambroxol has also demonstrated its antioxidant properties and is documented in several studies protecting against the oxidative stress by free radicals as derived from tobacco smoke and other toxic inhalants. Anti-inflammatory properties of ambroxol were demonstrated in several studies. N-acetyl cysteine (NAC), is a powerful antioxidant with mucolytic action. NAC is a precursor of L-cysteine that results in glutathione elevation biosynthesis. It acts directly as a scavenger of free radicals, especially oxygen radicals. Additionally, NAC is a mucolytic drug that mellows tenacious mucus discharges.

RATIONALE FOR CONDUCTING THIS STUDY:

Ambronac tablet is a fixed-dose combination (FDC) that contains two mucolytic agents N-Acetyl L-Cysteine – 200 mg and Ambroxol hydrochloride 30 mg. It claims to be a very safe and effective treatment for respiratory diseases. It is in the market for the past few years and is useful for ailments like COPD and chronic bronchitis. As a mechanism of mucolytic action of N-Acetylcysteine & Ambroxol is similar, these 2 agents will have an additive effect in mucolytic action. In this phase IV trial, safety and efficacy of aforesaid product will be assessed and the data will be a proof of concept for the claims made. The present study intends to further show the safety and efficacy ofAmbronac claiming a unique cure on bronchitiswith excess mucus productionin 200 subjects.

Two hundred patients with bronchitis selected from OPD of the selected hospitals (sites) will be included in this multi-center, single-arm study. Patients will complete a screening visit (V1) to determine eligibility for the study based on Inclusion & Exclusion Criteria, patient history, and safety measures

The duration of each patient’s participation in the study will be of 1 week (7 days). Scheduled study visits will include:

•           Visit 1 (Screening on Day 0)

•           Telephonic interview (Day 3)

•           Visit 2 (End of study visit on Day 7)

During Visit 1 (Screening), informed consent will be obtained before any study procedures take place. After a patient has consented, medical history will then be documented, including the concomitant medications. All patients will undergo the screening procedure by inclusion and exclusion criteria. Demography, physical examination will be recorded. The patient’s peak expiratory flowwill be measured. Female patients of childbearing age will undergo a urine pregnancy test. Subjective assessment of bronchitis using the SGRQ questionnaire and quality of life assessment using EQ5D- 5L will be done. Patients will be given instructions for the next visit.

Patients will be contacted telephonically on Day 3. They will be asked about adverse events or any other   problem.

At Visit 2 (End of Study Visit), patients will visit the site on Day 7. The patient’s peak expiratory flow will be measured. Subjective assessment of bronchitis using the SGRQ questionnaire and quality of life assessment using EQ5D- 5Lwill be done.

DISCUSSION AND OVERALL CONCLUSIONS-

The objective of thissingle arm, multicentric study was to evaluate safety and efficacy of Ambronactablets in patients with bronchitis and having excess mucus production. Twohundred patients that included 165 male and 35 female patients of bronchitiswere enrolled in the study. All 200 patients completed the study and receivedfull dose of Ambronac tablets. Safety was one of the primary objective of the study.Safety analysis was done on safety population. There were no alarming safetyissues observed during the study period. All the adverse events were mild innature and probably related to the study drug administered. Commonly reportedadverse events were transient. Efficacy was the secondary objective of thestudy. Efficacy analysis was done on ITT population. At the end of 7 days oftreatment with study medication, positive results were observed in all endpoints analyzed except two of the parameters assessed in SGRQ questionnaire.Statistically significant difference was observed in almost all secondaryanalyses with respect to efficacy parameters of oral Ambronac tablets inpatients suffering from bronchitis. Encouraging results were exhibited by treatmentof oral Ambronac tablet in case of bronchitis symptoms showing improvementstatus of all patients. Peak expiratory rate assessing airway obstruction ofthe patient also showed significant improvement after 7 days treatment.Similarly, good results were observed in impact score of SGRQ questionnairewhich is the broadest component of the questionnaires, covering the whole rangeof disturbances that respiratory patients experience in their lives and EQ5D-5L questionnaire assessing health status of the patient before and after thetreatment. Based on statistical analysis of this trial data, we can concludethat Ambronac tablets exhibit impressive efficacy along with acceptable safety.Overall, the incidence of TEAEs in this trial was consistent with the knownsafety profile of Ambronac Tablets and did not reveal any new safety signal forit.