Clinical trial NCT03837938: Clinical Trial of Efficacy and Safety of Levopront® 30 mg/5 ml in Patients With Dry Cough
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cough
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2019-02-12
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: Inclusion Criteria:

Subjects should meet the following inclusion criteria to be included into this clinical trial:

1. Signed Informed Consent Form
2. Male or female aged from 18 to 65 (inclusive)
3. Dry non-productive cough as a symptom of acute upper respiratory infection (IDC codes J00-J06)
4. Daytime cough symptom score ≥ 3 points according to the "Six-point daytime and nighttime cough assessment scale"
5. 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
6. Patient's consent to follow the protocol procedures, including the completion of the patient's diary
7. 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:

1. Hypersensitivity or individual contraindications to Levodropropizine, Prenoxdiazine or additives of the study drug
2. Hereditary fructose intolerance, glucose-lactose malabsorption, lactase deficiency, sucrose-isomaltose deficiency
3. 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
4. Inhalation anesthesia within 3 months before screening
5. Smoking history of more than 10 pack-years
6. Previous use of cough medicines, ACE inhibitors or amiodarone within 30 days before screening
7. Contraindications or inability to perform spirometry
8. Necessity (in the Investigator's opinion) of prescribing mucolytic agents, expectorants, antibiotics or other medications prohibited by the protocol during the study
9. 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)
10. Malignant tumors in the past 5 years (except for the basal cell carcinoma)
11. 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
12. Gastric or duodenal ulcers, gastroesophageal reflux disease within a period of 12 months before screening
13. Systemic autoimmune disorders and connective tissue diseases that require (currently or previously) administration of systemic glucocorticosteroids, cytostatic medications or penicillamine
14. 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
15. 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
16. Taking part in another clinical trial or use of study drug within 30 days before screening
17. 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
18. 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.

Primary outcomes:
measure: Number of Participants With Daytime Cough Resolution Rate by Day 8 in the PP Population
timeFrame: At Visit 3, Day 8
measure: Number of Participants With Daytime Cough Resolution Rate by Day 8 in the ITT Population
timeFrame: At Visit 3, Day 8
Secondary outcomes:
measure: Number of Participants With Nighttime Cough Resolution Rate by Day 8 in the ITT Population
timeFrame: At Visit 3, Day 8
measure: Number of Participants With Daytime & Nighttime Cough Symptoms Resolution in the ITT Population
timeFrame: At Visit 2, Day 4
measure: Change From Baseline in Severity and Frequency of Daytime and Nighttime Cough According to "Six-point Daytime and Nighttime Cough Assessment Scale" in the ITT Population
timeFrame: Baseline, At visit 2 Day 4; at visit 3, Day 8
measure: Change From Baseline in Cough Intensity According to the Visual-analogue Scale (VAS) in the ITT Population.
timeFrame: Baseline, At visit 2 (Day 4); at visit 3 (Day 8)
measure: Change From Baseline in Pre-bronchodilator FEV1 Values on Day 8 in the ITT Population.
timeFrame: At Visit 3 (Day 8)
measure: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) of the Various Severity According to Subjective Complaints
timeFrame: From the moment of signing Informed Consent Form (prior to administration of the first dose of the study drug) to Day 30 after the last visit of the patient or last procedure per protocol, up to day 10"
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: State Public Healthcare Institution of Moscow "City Clinical Hospital # 71 of Moscow Healthcare Department"
city: Moscow
country: Russian Federation
facility: The Laboratory of Pulmonology, State Budgetary Educational Institution of Higher Professional Education "Moscow State Medical-Stomatological University n.a. A.I. Evdokimov" under Ministry of Health of the Russian Federation (Clinical base of state budget
city: Ryazan
country: Russian Federation
facility: State Budgetary Educational Institution of Higher Professional Education "Ryazan' State Medical University n.a. academician I.P. Pavlov" under Ministry of Health of the Russian Federation
city: Saint-Petersburg
country: Russian Federation
facility: "Institute of Medical Research" LLC
city: Saint-Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution "Nikolaevskaya Hospital"
city: Saratov
country: Russian Federation
facility: State Healthcare Institution "Regional Clinical Hospital"
city: Smolensk
country: Russian Federation
facility: LLC Treatment-and-prophylactic institution on the "Smolensk clinic"
city: Yaroslavl
country: Russian Federation
facility: State Autonomous Healthcare Institution of Yaroslavl Region "Clinical Hospital of Emergency care n.a. N.V. Solovyev"
Study officials:
affiliation: Dompé SpA Milan
name: Federico Saibene, MD
role: STUDY_DIRECTOR
References: