Mucolytic Effectiveness of Tacholiquine ® in Chronic Bronchitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the mucolytic activity of Tacholiquine® compared to saline (0.9%) in chronic bronchitis patients. Lung function parameters, biomarker profiles in sputum and serum, and clinical symptoms by standardized questionnaires [COPD activity index (CAT), Baseline Dyspnea Index (BDI) & Transition Dyspnea Index (TDI)and the St. George's Respiratory Questionnaire (SGRQ)] will be evaluated in response to Tacholiquine® vs. saline in chronic bronchitis patients.

Detailed Description
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The aim of the study is to compare Tacholiquine ® and saline (0.9%) regarding their ability to promote the discharge of mucus from the respiratory passages in patients with chronic bronchitis (COPD). Alleviated discharge of mucus should ease breathing, improve subjective wellbeing, reduce inflammation in the air passages and improve lung function. Determine the magnitude of the effect of Tacholiquine ® compared to saline (0.9%) in chronic bronchitis patients. Lung function parameters, biomarker profiles in sputum and serum, and clinical symptoms and quality of life by standardized questionnaires [COPD activity index (CAT), Baseline Dyspnea Index (BDI) & Transition Dyspnea Index (TDI), St George's respiratory Quality of Life Questionnaire] will be evaluated in response to Tacholiquine ® vs. saline at day one and at end of treatment.

Official Title
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A Double-blind, Placebo Controlled, Randomized Crossover Trial to Characterize the Mucolytic Effectiveness of Tacholiquine® in Chronic Bronchitis

Conditions
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Bronchitis, Chronic, Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tacholiquine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures. Female or male subjects aged 40-85 years inclusive at Visit 1. Documented history of COPD with a post-bronchodilator FEV1/FVC<0.70 and a post-bronchodilator FEV1<80% of predicted normal value at screening (spirometry will be used for this criteria assessment). Current smoker or ex-smoker with a tobacco history of ≥10 pack-years (1 pack year = 20 cigarettes smoked per day for 1 year). Women of childbearing potential (WOCBP) must use a highly effective form of birth control (confirmed by the Investigator). - Women >50 years old would be considered postmenopausal At least a CAT value > 10 at Visit 1. Presence of chronic cough and sputum production either several days per week or almost every day Exclusion Criteria: Clinically important pulmonary disease other than COPD (e.g. active lung infection, clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency and primary ciliary dyskinesia) or another diagnosed pulmonary or systemic disease that is associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome). Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: Affect the safety of the subject throughout the study Influence the findings of the study or their interpretation Impede the subject's ability to complete the entire duration of study Documented Unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure, renal failure, uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator that in Investigator's judgment may put the patient at risk or negatively affect the outcome of the study. Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 4 weeks prior to (Visit 1). Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 4 weeks prior to (Visit 1). Pneumonia within 4 weeks prior to (Visit 1), based on the last day of antibiotic treatment or hospitalization date, whatever occurred later. The subject cannot be re-screened if this exclusion criterion is met. History of anaphylaxis to Tacholiquine®. Long term oxygen therapy (LTOT) defined as need for oxygen > 4L 02 flow with signs and/or symptoms of cor pulmonale, right ventricular failure or evidence by echocardiogram or pulmonary artery catheterization of moderate to severe pulmonary hypertension. In order to be admitted to the trial subjects on LTOT have to be ambulatory and be able to attend clinic visits. Any clinically significant abnormal findings in physical examination, vital signs, hematology, or urinalysis during Visit 1, which, in the opinion of the Investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to complete entire duration of the study. Use of immunosuppressive medication, including rectal corticosteroids, high potency topical corticosteroids and systemic steroids within 28 days prior to (Visit 1).

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tacholiquine<br>Inhalation | Drug: Tacholiquine<br>* Inhaled Tacholiquine ®1% - 5ml<br>|
| Placebo Comparator: Saline Solution 0,9%<br>Inhalation | Other: Placebo<br>* Inhaled Placebo<br>* Other names: isotonic saline solution (0.9%);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of sputum weight before, during and after treatment | Active Treatment for 3 weeks compared with Placebo (Saline solution 0.9%), 3 inhalations with 5 ml solution via nebulizer per day of study treatment during 21 consecutive days | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COPD Assessment Test (CAT) | Symptom Score | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| Baseline Dyspnoea Index (BDI) | Symptom Score | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| transition dyspnoea index (TDI) | Symptom Score | Visit 1 (day 0), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 6 (day 21±3 after Visit 4) | 
| ease of sputum production | Ease is measured by analog scale | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| Change in Forced vital capacity (FVC) | lung function parameter | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| change in forced expiratory volume at one second (FEV1) | lung function parameter | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| Forced Expiratory Flow at 75% (FEF25) | lung function parameter | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| Residual Volume (RV) | lung function parameter | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| Ratio of Residual Volume to Total Lung Capacity( RV/TLC) | lung function parameter | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| Sputum biomarker profiles (IL-1, IL-6, IL-8) |  | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| CrP | Plasma biomarker profile | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| Lipopolysaccharide-binding protein (LBP) | Plasma biomarker profile | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) | 
| Interleukin 6 (IL-6) | Plasma biomarker profile | Visit 1 (day 0), Visit 2 (day 7 ±1), Visit 3 (day 21±3), Visit 4 (day 28±3), Visit 5 (day 7±1 after Visit 4), Visit 6 (day 21±3 after Visit 4) |