Clinical Trial of Efficacy and Safety of Levopront® 30 mg/5 ml in Patients With Dry Cough

Study Overview
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Brief Summary
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Primary objective: To assess the efficacy of Levopront® in comparison with Libexin® based on daytime cough resolution rate by Day 8. The daytime cough symptoms resolution corresponds to 0 or 1 points on the Six-point daytime and nighttime cough assessment scale. Secondary objectives: Treatment effect assessment in terms of the following efficacy and safety parameters: To assess the efficacy of Levopront® in comparison with Libexin® based on nighttime cough resolution rate by Day 8. Daytime and nighttime cough symptoms resolution according to Six-point daytime and nighttime cough assessment scale by Day 4. Change in severity and frequency of daytime and nighttime cough according to Six-point daytime and nighttime cough assessment scale on Day 4 and Day 8 from baseline on Day 1. Cough intensity change according to the visual-analogue scale on Day 4 and Day 8 from baseline on Day 1. Change of FEV1 on Day 8 from baseline values on Day 1. Rate of Adverse events (AE) and Serious Adverse Events (SAE) of the various severity according to subjective complaints, laboratory test results, physical examination, vital signs and spirometry

Detailed Description
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This is a multicenter, open-label, randomized, clinical trial to assess the efficacy and safety of Levopront® syrup 30 mg/5 ml in comparison with Libexin® 100 mg tablets in patients suffering from dry non-productive cough caused by acute upper respiratory infection

Official Title
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Multicenter Open-label Randomized Clinical Trial of the Efficacy and Safety of Levopront® Syrup 30 mg/5 ml in Comparison With Libexin® 100 mg Tablets in Patients With Dry Non-productive Cough Caused by Acute Upper Respiratory Infection

Conditions
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Cough

Intervention / Treatment
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* Drug: Levopront® syrup 30 mg/5 ml
* Drug: Libexin®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects should meet the following inclusion criteria to be included into this clinical trial: Signed Informed Consent Form Male or female aged from 18 to 65 (inclusive) Dry non-productive cough as a symptom of acute upper respiratory infection (IDC codes J00-J06) Daytime cough symptom score ≥ 3 points according to the Six-point daytime and nighttime cough assessment scale Pre-bronchodilator FEV1 ≥ 70% of the predicted values, post-bronchodilator FEV1 increase of ≤ 12% or ≤ 200 ml compared to the baseline, FEV1/FVC (Tiffeneau index) ≥ 0.7 Patient's consent to follow the protocol procedures, including the completion of the patient's diary Patient's consent to use the adequate contraception methods throughout the study period. The adequate birth control methods are as follows: Oral or transdermal contraceptives Condoms or diaphragms (barrier method) with spermicide Intrauterine contraceptive devices Exclusion Criteria: Subjects with any of the following conditions will be excluded from the study: Hypersensitivity or individual contraindications to Levodropropizine, Prenoxdiazine or additives of the study drug Hereditary fructose intolerance, glucose-lactose malabsorption, lactase deficiency, sucrose-isomaltose deficiency Tuberculosis, bronchial asthma, malignant tumors of lungs or bronchi, COPD, severe respiratory failure (cyanosis, need for respiratory support) or other lung pathology at screening or in history Inhalation anesthesia within 3 months before screening Smoking history of more than 10 pack-years Previous use of cough medicines, ACE inhibitors or amiodarone within 30 days before screening Contraindications or inability to perform spirometry Necessity (in the Investigator's opinion) of prescribing mucolytic agents, expectorants, antibiotics or other medications prohibited by the protocol during the study Excessive mucous excretion which (in the Investigator's opinion) could be a contraindication to prescribing anti-cough medicines; decreased mucociliary function (Kartagener's syndrome, ciliary dyskinesia) Malignant tumors in the past 5 years (except for the basal cell carcinoma) Serious cardiovascular disease at the moment or within 12 months prior to screening, including: Chronic heart failure class III or IV (according to the classification of the New York Heart Association), severe arrhythmias requiring treatment with antiarrhythmic drugs class Ia, Ib, Ic or III, unstable angina, myocardial infarction, heart surgery and coronary arteries, serious valvular heart disease, transient ischemic attack or stroke, uncontrolled hypertension with systolic blood pressure > 180 mmHg and diastolic blood pressure > 110 mmHg, pulmonary embolism or deep vein thrombosis Gastric or duodenal ulcers, gastroesophageal reflux disease within a period of 12 months before screening Systemic autoimmune disorders and connective tissue diseases that require (currently or previously) administration of systemic glucocorticosteroids, cytostatic medications or penicillamine Signs of intensive non-controlled concurrent disease, including disorders of the nervous system, endocrine system, kidneys, liver or gastrointestinal tract, which (in the Investigator's opinion) could prevent the patient's participation in the study History of alcohol or drug abuse at screening or in the past, which results in the inability of the patient to participate in the study at the Investigator's discretion Taking part in another clinical trial or use of study drug within 30 days before screening Pregnant or breast-feeding women or women planning pregnancy during the clinical trial; women of childbearing potential (including not sterilized operatively and in postmenopausal period of less than 2 years), not using appropriate methods of contraception Inability to read or write; unwillingness to understand and follow the procedures of the study protocol; violation of the drug administration regimen or procedure execution that, at the discretion of the Investigator, can impact he results of the study or safety of the patient and interfere his further participation in the study; any other concomitant medical or serious mental conditions that make the patient unsuitable for participation in the clinical study, limit the validity of receiving an informed consent or may affect the patient's ability to participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levopront® syrup 30 mg/5 ml<br>Levopront® (levodropropizine) syrup 30 mg/5 ml 10 ml t.i.d. for 7 days The study drugs will be taken t.i.d. (with the interval of not less than 6 hours, between meals) during 7 days. | Drug: Levopront® syrup 30 mg/5 ml<br>* The first study drug administration will be performed at the clinical site on the day of randomization; the last study drug administration will be performed in the evening before Day 8 (±1).<br>* Other names: levodropropizine;|
| Active Comparator: Libexin® 100 mg tablets<br>Libexin® (prenoxdiazine) 100 mg tablets 1 tablet t.i.d. for 7 days. | Drug: Libexin®<br>* The first study drug administration will be performed at the clinical site on the day of randomization; the last study drug administration will be performed in the evening before Day 8 (±1).<br>* Other names: prenoxdiazine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daytime cough resolution rate by Day 8 - Levopront® vs Libexin® | The daytime cough symptoms resolution corresponds to 0 or 1 points on the Six-point daytime and nighttime cough assessment scale. | Daytime by Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nighttime cough resolution rate by Day 8 - Levopront® vs Libexin® | Efficacy comparative assessment | Nighttime by Day 8 | 
| Daytime and nighttime cough symptoms resolution daytime and nighttime cough assessment scale | Daytime cough (scoring during >08:00 up to 22:00 h) evaluated on a 6-point scale: 5 = no cough during the day to 0 = distressing coughs most of the day. Night-time cough (scoring during >22:00 up to 08:00 h) evaluated on a 6-point scale: 5 = no cough during the night to 0 = distressing coughs preventing any sleep. | Daytime by Day 4 | 
| Change in severity and frequency of daytime and nighttime cough according to Six-point daytime and nighttime cough assessment scale | Daytime cough (scoring during >08:00 up to 22:00 h) evaluated on a 6-point scale: 5 = no cough during the day to 0 = distressing coughs most of the day. Night-time cough (scoring during >22:00 up to 08:00 h) evaluated on a 6-point scale: 5 = no cough during the night to 0 = distressing coughs preventing any sleep. | Day 4 and Day 8 | 
| Cough intensity change according to the visual-analogue scale. | A 100 mm scale between 'no cough' (0) and 'the worst cough severity' (100) | Day 4 and Day 8 | 
| Change of FEV1 on Day 8 from baseline values. | Forced expiratory volume in 1 second. | Day 8 |