E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Inflammation of the nasal mucosa (called also “rhinitis“) and of the paranasal sinuses (“sinusitis”). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052106 |
E.1.2 | Term | Rhinosinusitis |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the present trial is the assessment of the efficacy of three different total daily doses of the investigational product containing 600 mg acetylcysteine per effervescent tablet compared to placebo for the treatment of acute uncomplicated rhinosinusitis. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the present trial is the assessment of safety and tolerability of three different total daily doses of the investigational product containing 600 mg acetylcysteine per effervescent tablet compared to placebo for the treatment of acute uncomplicated rhinosinusitis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
[1] Male or female subjects aged between 18 and 75 years inclusive on the date of consent [2] Diagnosis of acute, uncomplicated rhinosinusitis defined at screening Visit 1 and at Visit 2 as: a) major symptom score (MSS) assessed by the patient ≥8 and ≤12 points for the following: rhinorrhea/ anterior discharge, postnasal drip, nasal congestion, headache, and facial pain/pressure, whereupon the nasal congestion is mandatory and no more than 3 of the 5 symptoms are rated as severe b) individual score for facial pain/pressure ≥1 (mild) and ≤2 (moderate) c) presence of symptoms ≤3 days prior to screening visit [3] Informed consent to participate in the trial provided in written form. |
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E.4 | Principal exclusion criteria |
[1] History of hypersensitivity or intolerance to the active substance or any of the excipients of the trial medication [2] Patient with history of hereditary fructose intolerance, galactose intolerance, lactase deficiency or glucose-galactose malabsorption [3] Chronic rhinosinusitis (symptoms lasting longer than 3 months) [4] Subjects who have undergone sinus or nasal surgery for chronic rhinosinusitis in the 6 months prior to screening visit [5] Sinus lavage within 7 days prior to screening visit [6] Odontogenic rhinosinusitis [7] Allergic (perennial or seasonal) rhinitis [8] Bronchial asthma or chronic obstructive pulmonary disease [9] Nasal polyposis or clinically relevant nasal septum deviation [10] Concomitant otitis [11] Intranasal or systemic use of corticosteroids within 30 days prior to screening visit [12] Intranasal or systemic use of antibiotics within 30 days prior to screening visit [13] Use of nasal decongestants within 2 days prior to screening visit [14] Concomitant treatment of common cold-like symptoms within 7 days prior to screening visit with any of the following: a) Analgesics b) Non-steroidal anti-inflammatory drugs c) Antihistamines [15] Concomitant use of intranasal saline irrigation [16] Use of immunosuppressive agents within 30 days prior to screening visit [17] Immunocompromised state [18] Suspicion for acute bacterial rhinosinusitis (defined as presence of purulence for 3 to 4 days with fever ≥ 38.3°C) [19] Pregnant or breast-feeding female patient [20] Female patient of childbearing potential (not surgically sterilized/ hysterectomized or postmenopausal for at least 1 year) who is not currently using (documented at screening visit) and not willing to use medically reliable methods of contraception for the entire trial duration such as oral, injectable or implantable contraceptives, intrauterine contraceptive devices (IUD), sexual abstinence or vasectomized partner [21] Any other condition of the patient (e.g. serious or unstable medical or psychological condition, acute psychosis) that in the opinion of the investigator may compromise evaluation of the trial treatment or may jeopardize patient’s safety, compliance or adherence to protocol requirements [22] Participation in ANY research study involving another investigational medicinal product (IMP) within 30 days prior to screening visit, or simultaneous participation in another clinical study or previous participation in present study [23] Suspected alcohol/ drug dependence or abuse (including heavy smoking: ≥ 20 cigarettes daily) [24] Use of snuff tobacco [25] Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the trial [26] Subjects who are known or suspected: - not to comply with the trial directives - not to be reliable or trustworthy - to be a dependent person, e.g. a relative, family member, or member/ employee of the investigator’s or sponsor’s staff - subject is in custody or submitted to an institution due to a judicial order.
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline in the daily MSS over the entire treatment period. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After the end of the clinical part of the trial, following database lock and unblinding. |
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E.5.2 | Secondary end point(s) |
Secondary endpoints are: Time to onset of action defined as first day of active treatment on which MSS shows statistically significant difference from placebo; MSS (major symptom score) development over the course of the study; SNOT-22 (sino-nasal outcome test) by visit and changes versus baseline; Percentage of responders and non-responders to treatment based on the assessment of overall response to treatment by the investigator.
The safety endpoints are: • Incidence and severity of adverse events • Incidence and severity of drug-related adverse events • Clinically relevant changes in laboratory parameters, vital signs, physical and ENT examination parameters from Visit 1 to Visit 6 (or early termination) • Overall assessment of tolerability by patient and by investigator. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After the end of the clinical part of the trial, following database lock and unblinding. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Germany |
Moldova, Republic of |
Russian Federation |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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VISIT 6 on Day 15 (+3) is the last regular visit (LVLS). A FOLLOW-UP PHONE CALL (within 7 days after Visit 6) is planned to be performed. During the phone call the investigator will check if any AE occurred after Visit 6 and if medically required the patient can be invited for additional (not trial related) visits. The date of the last follow up call of the last patient in the trial will be defined as the end of the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |