A Clinical Trial Investigating the Short-term Relief of Symptoms of Acute Pharyngitis by Treatment With Three Different Doses of MYRAMISTIN™ Oromucosal Spray

Study Overview
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Brief Summary
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In this multi-center, randomized, placebo-controlled, double-blind stuy in which patients with acute pharyngitis will receive Myramistin™ / Placebo, which is provided as a spray. Patients will be randomised at Visit 1 on a 1:1:1:1 basis to one of the three MyramistinTM doses (0.005%, 0.01% and 0.02%) or placebo. The trial duration for an individual patient is 72 hours. The primary objective is to evaluate the short-term efficacy of different MyramistinTM doses (0.005%, 0.01% and 0.02%) compared to placebo in the symptomatic treatment of acute pharyngitis.

Official Title
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A Multi-center, Randomized, Placebo-controlled, Double-blind, Dose-finding Clinical Trial Investigating the Short-term Relief of Symptoms of Acute Pharyngitis Such as Throat Soreness Pain and Difficulty to Swallow by Treatment With Three Different Doses of MYRAMISTIN™ Oromucosal Spray

Conditions
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Acute Pharyngitis

Intervention / Treatment
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* Drug: Myramistin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female at the ages of 18 to 75 years Body Mass Index (BMI): 18-31 kg/m2 Willing and able to give informed consent Clinically diagnosed acute pharyngitis. Onset of symptoms of acute pharyngitis within the past 48 hours prior to Visit 1 Symptoms of acute pharyngitis such as sore throat and difficulty to swallow Sore throat pain intensity scored as at least 60 mm on a 0-100 mm VAS (Visual Analogue Scale) Sore Throat Pain Intensity Scale (STPIS) Difficulty in swallowing of at least 60 mm on a 0-100 mm VAS Difficulty Swallowing Scale (DSS) Tonsillo-Pharyngitis Assessment (TPA) ≥ 6 on 21-point TPA- scale Absence of Group A Streptococcus as confirmed by a rapid swab test before randomization McIsaac - Score <3 Willing to stay in the trial center for at least 2 hours (maximum 3 hrs) after the first dose and return after 72 hours treatment on Day 4 Willing not to take anything by mouth excluding the investigational medical product (IMP) and / or unable to abstain from smoking during the stay in the trial center. Drinking of water is allowed. Female patients must have either a negative pregnancy test at Visit 1 and practicing a reliable method of contraception used consistently and correctly (including oral contraceptives, hormone implant, intrauterine device), or must be postmenopausal (not spontaneous menstrual periods for at least 6 months) or must be surgically sterile (tubal ligation or removal of ovaries or uterus) Exclusion Criteria: Patients with strong suspicion of Group A streptococcus infection. Either swab test is positive OR McIsaac Score ≥ 3 points Presence of signs or symptoms of any acute infection for which treatment with antibiotics is mandatory and/or should not be postponed; i.e. accompanied fever (> 38°C at Visit 1) and/or - if visually identified pharyngeal - presence of seropurulent, purulent, fibro serous or fibrinous exudate from the pharyngeal mucosa Patients with allergies or bronchial asthma who have a history of exacerbations within 30 days prior to trial inclusion The use of any systemic analgesics / local analgesics in the throat area (e.g. Acetyl Salicylic Acid = ASA > 100 mg) during the trial or within 12 hours prior first study medication application. Exception Paracetamol: intake of Paracetamol is allowed up to 6 hours before first application of IMP The use of systemic antibiotics / local antibiotics in the throat area during the trial and within the previous 7 days prior to Visit 1 The use of any systemic or local (i.e. in the throat area) antihistamines started within 2 weeks prior to Visit 1 The use of any systemic anti-inflammatory drug / local anti-inflammatory drug in the throat area (e.g. non-steroidal anti- inflammatory drugs or glucocorticoids) during the trial or within 12 hours prior to first IMP application The use of local anaesthetics for treatment of sore throat during the trial or within 12 hours prior to first IMP application The use of any other 'sore throat medication' (e.g. lozenges, drops, sprays, decongestants) or other 'cold medication' that could interfere the trial results within the previous 12 hours prior to first study medication application Major wounds of the mouth and throat Immunodeficiency disorders (e.g. organ transplantation, HIV infection) Existing cardiac, haematological, hepatic, renal, gastrointestinal, metabolic and / or pathological findings, which might interfere with the drug's safety, tolerability and / or absorption according to the judgement of the Investigator Any neurological or psychiatric conditions, which might give the impression that the patients will not comply with the protocol and trial needs Patients with history (previous 5 years) or present condition of any malignancy Known hypersensitivity to any ingredient of MyramistinTM Previous participation in the trial Parallel participation in any other trial during the previous 90 days before screening History of alcohol or drug abuse Known or suspected of being unable to comply with the clinical trial protocol (e.g. no permanent address, history of drug abuse, known to be non-compliant or presenting an unstable psychiatric history) Legal incapacity and / or other circumstances rendering the patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Myramistin 0.005%<br> | Drug: Myramistin<br>* Oromucosal application<br>|
| Experimental: Myramistin 0.01%<br> | Drug: Myramistin<br>* Oromucosal application<br>|
| Experimental: Myramistin 0.02%<br> | Drug: Myramistin<br>* Oromucosal application<br>|
| Placebo Comparator: Placebo<br> | Drug: Myramistin<br>* Oromucosal application<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Differences | The primary endpoint is the Summed Pain Intensity Differences (SPID-2Pain), defined as Pain Intensity Differences (PID) summarized over the time course of 2 hours after first application on Day 1 (Baseline). The sum is calculated over the time-weighted differences from each measured time point to baseline after dosing using the 100mm Visual Analogue Scale (VAS) Sore Throat Pain Intensity Scale (STPIS). | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Differences | Pain Intensity Differences (PID) is summarized at different defined timepoints after first application on Day 1 (Baseline). The sum is calculated over the time-weighted differences from each measured time point to baseline after dosing using the 100mm VAS Sore Throat Pain Intensity Scale (STPIS). | 72+/-2 hours | 
| Difficulty to Swallow Differences | SPID2-Swallow calculated analogously to the primary endpoint (including sensitivity analysis) using the Difficulty Swallowing Scale (DSS), furthermore it is calculated on different predefined timepoints. | 72+/-2 hours | 
| Time to Pain Relief | Time to 30% and 50% pain relief (30% and 50% reduction in STPIS) compared to baseline. | 72+/-2 hours | 
| Time to relief in Difficulty to Swallow | Time to 30% and 50% relief in difficulty in swallowing (30% and 50% reduction in DSS) compared to baseline. | 72+/-2 hours | 
| Percentage of symptom free patients | in throat pain at Visit 2 (STPIS=0) in difficulty in swallowing at Visit 2 (DSS=0) in throat pain and difficulty in swallowing at Visit 2 (STPIS=0 and DSS=0 - defined as complete | 72+/-2 hours | 
| Tonsillo-Pharyngitis Assessment Scale | Change in Tonsillo-Pharyngitis Assessment (TPA) sum-score and single symptom scores from baseline to Visit 2 Variables (findings like e.g. oral temperature, oropharyngeal colour, size of tonsilles etc.) presented are rated using the values 0, 1, 2 or 3 (points). The points are added together to make a TPA that can range from 0 to 21 points. Pharyngitis is present if a total score of ≥6 is obtained. | 72+/-2 hours |