Efficacy and Safety of Dioxidin Versus Miramistin in Superficial Pyoderma

Study Overview
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Brief Summary
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The study is aimed to: evaluate the effectiveness of 10-day therapy with Dioxidin® compared with Miramistin® in the treatment of superficial pyoderma, evaluate the safety and tolerability of 10-day therapy with Dioxidin® compared with Miramistin® for the treatment of superficial pyoderma.

Official Title
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Opened, Multicenter, Randomized, in Parallel Groups Comparative Study to Assess Efficacy and Safety of Dioxidin®, Solution for Topical and External Application 0.025% (Valenta Farm, Russia) and Miramistin®, Solution for Topical Application 0.01% (Infamed K LLC, Russia) in Treatment of Superficial Pyoderma

Conditions
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Pyoderma

Intervention / Treatment
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* Drug: Hydroxymethylquinoxalindioxyde
* Drug: Benzyl-dimethyl-[3-(tetradecanoylamino)propyl]azanium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women between the ages of 18 and 65 years inclusive. Signed informed consent form to participate in the study. Patients with superficial pyoderma of different localization. Body surface lesion area ≤ 5%. Patient's willingness and ability to comply with protocol requirements throughout the study (in particular, willingness to adhere strictly to the prescribed treatment regimen and to record the time of drug administration in the patient's diary). Consent of study participant with preserved reproductive potential to use adequate methods of contraception (e.g., dual barrier method) throughout the study and for 3 weeks after study completion. Exclusion Criteria: Hypersensitivity to the active and/or excipients of the studied drugs. Presence of signs of acute respiratory infections. Deep pyoderma (furunculus, carbuncle, abscess, hydradenitis, etc.). Use of local and systemic antibacterials, antiseptics, glucocorticosteroids, and antifungal agents less than 14 days prior to the screening visit. Presence of infectious diseases requiring topical and/or systemic antibacterial therapy. Vaccination of the patient less than 1 week prior to the screening visit. Adrenal insufficiency. Body temperature >37C. Fungal, viral skin infections, severe generalized bacterial skin lesions, other skin diseases. Immunodeficiency states. Positive HIV, Hepatitis B and C, or syphilis, or SARS-CoV-2 rapid test (COVID-19) Presence of at least one of the following epidemiologic indicators: Return from foreign travel 7 days prior to screening; Close contact in the last 7 days prior to screening with an individual under observation for COVID-19 who subsequently became ill; Close contact in the last 7 days prior to screening with an individual with a laboratory confirmed diagnosis of COVID-19; Professional contacts in the last 7 days prior to screening with individuals who have a suspected or confirmed case of COVID-19. Scalp lesion (where treatment procedures and effectiveness cannot be adequately evaluated due to thick/long hair). Allergic reactions to antibacterial drugs, antiseptic drugs in history. Diabetes mellitus type 1 or 2. Any other comorbidities or conditions that, in the opinion of the investigator, make it difficult to interpret treatment results or make it impossible to perform procedures in this clinical trial or pose a risk to the patient when participating in the study (e.g., a history of severe allergies, atopic dermatitis in case the affected area overlaps with the area of pyoderma). History of malignancy, with the exception of patients who have not had the disease in the past 5 years, patients with fully cured basal cell carcinoma of the skin, or fully cured carcinoma in situ. Severe, decompensated, or unstable somatic diseases (any disease or condition that is life-threatening or worsens the patient's prognosis, or makes it impossible for the patient to participate in a clinical trial). The need for concomitant therapy with any of the drugs listed as Prohibited Concomitant Treatment. History of alcohol and/or drug dependence. Participation in another clinical trial less than 3 months prior to the Screening Visit. Pregnancy. Breastfeeding period. Withdrawal Criteria: Withdrawal of Informed Consent by the patient. Patient does not meet inclusion criteria. Patient is found to have non-inclusion criteria. Patient's desire to stop their participation in the study at any stage of the study. Researcher's decision that continued participation in the study is contrary to the patient's best interests. The investigator's decision to exclude the patient from the study due to a serious deviation from/breach of protocol. Identification of a probable or confirmed COVID- 19 case (according to the Standard COVID-19 case definition). An undesirable event requiring withdrawal of study therapy, or prescription of drugs from the Prohibited Complementary Treatment section, or limiting protocol procedures. Patient's failure to show up for any visit and loss of communication with the patient. Patient's omission of a cumulative total of more than 5 doses of medication throughout the treatment period or 3 consecutive doses. Pregnancy. Termination of the study by the sponsor. Termination of the study by the investigator. Termination of the study by the regulatory agency.

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: Dioxidin<br>Patients will apply Dioxidin® 3 times a day (in the morning, afternoon and evening) by spraying (4 pressings of the spray nozzle on each affected area corresponding to 1% of the body area) on the affected skin areas from a distance of about 10 cm, so that the entire affected surface is covered with the solution. After application, you should wait until the preparation is completely dry. The therapy duration will be 10 days. | Drug: Hydroxymethylquinoxalindioxyde<br>* Dioxidin®, 0.025% solution for local and external use (Valenta Farm, Russia).<br>* Other names: Dioxidin;|
| Active Comparator: Miramistin<br>Patients will apply Miramistin® to the affected areas of the skin by wiping with sterile gauze swabs liberally moistened with the preparation three times a day (in the morning, lunchtime, and evening). The therapy duration will be 10 days. | Drug: Benzyl-dimethyl-[3-(tetradecanoylamino)propyl]azanium<br>* Miramistin®, topical solution 0.01% (Infamed K LLC, Russia)<br>* Other names: Miramistin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who experienced complete cure of the disease at Visit 4 | In this study, cure will be considered achieved if the severity of each pyoderma symptom (painfulness on palpation, pustules/fluketens, hyperemia, inflammatory infiltration, edema) does not exceed 0 points (assessed from 0 [the absence of symptom] to 3 [maximal severity of the symptom]) | Day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in the arithmetic mean change in pyoderma symptom severity scale, to Visits 2, 3, and 4 compared to baseline. | Each symptom will be assessed from 0 (the absence of symptom) to 3 (maximal severity of the symptom) | Day 1, Day 4, Day 7, Day 10 | 
| Mean change in severity for the symptom soreness on palpation to Visits 2, 3 and 4 compared to baseline | The symptom will be assessed from 0 (the absence of symptom) to 3 (maximal severity of the symptom) | Day 1, Day 4, Day 7, Day 10 | 
| Average change in the severity for the symptom presence of pustules/flukteness to Visits 2, 3 and 4 compared to baseline | The symptom will be assessed from 0 (the absence of symptom) to 3 (maximal severity of the symptom) | Day 1, Day 4, Day 7, Day 10 | 
| Average change in the expression for the symptom hyperemia to Visits 2, 3 and 4 compared to baseline | The symptom will be assessed from 0 (the absence of symptom) to 3 (maximal severity of the symptom) | Day 1, Day 4, Day 7, Day 10 | 
| Mean change in severity for the symptom inflammatory infiltration to Visits 2, 3 and 4 compared to baseline | The symptom will be assessed from 0 (the absence of symptom) to 3 (maximal severity of the symptom) | Day 1, Day 4, Day 7, Day 10 | 
| Mean change in severity for the symptom swelling to Visits 2, 3 and 4 compared to baseline | The symptom will be assessed from 0 (the absence of symptom) to 3 (maximal severity of the symptom) | Day 1, Day 4, Day 7, Day 10 | 
| Average patient satisfaction with treatment at Visit 2, 3 and 4 | The satisfaction will be assessed from 0 (not satisfied) to 3 (absolutely satisfied) | Day 4, Day 7, Day 10 | 
| Safety and Tolerability: vital signs - systolic blood pressure (SBP) | SBP, mmHg | Screening, Day 1, Day 4, Day 7, Day 10 | 
| Safety and Tolerability: vital signs - diastolic blood pressure (DBP) | DBP, mmHg | Screening, Day 1, Day 4, Day 7, Day 10 | 
| Safety and Tolerability: vital signs - heart rate (HR) | HR, beats per minute | Screening, Day 1, Day 4, Day 7, Day 10 | 
| Safety and Tolerability: vital signs - body temperature | Body temperature, centigrade scale | Screening, Day 1, Day 4, Day 7, Day 10 | 
| Safety and Tolerability: physical examination results | Physical examination will follow the general rules of internal medicine: general examination, examination of mucous membranes and skin, including palpation of lymph nodes, evaluation of the musculoskeletal system, palpation, percussion, and auscultation of the main organ systems (cardiovascular, respiratory, digestive, and urinary systems) will be performed sequentially. The findings (if any) will be reported as the rate of clinically significant findings by each system level assessed. | Screening, Day 1, Day 4, Day 7, Day 10 | 
| Safety and Tolerability: complete blood count - hemoglobin | Hemoglobin, g/dL | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - red blood cells | Red blood cells, 10^6/uL | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - hematocrit | Hematocrit, % | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - platelets | Platelets, 10^3/uL | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - white blood cells | White blood cells, 10^3/uL | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - erythrocyte sedimentation rate | Erythrocyte sedimentation rate, mm per hour | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - lymphocytes | Lymphocytes, % | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - eosinophils | Eosinophils, % | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - monocytes | Monocytes, % | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - basophils | Basophils, % | Screening, Day 10 | 
| Safety and Tolerability: complete blood count - neutrophils | Neutrophils, % (segmented and stab) | Screening, Day 10 | 
| Safety and Tolerability: blood test results - glucose | Glucose in blood serum, mmol/L | Screening, Day 10 | 
| Safety and Tolerability: blood test results - total cholesterol | Total cholesterol in blood serum, mmol/L | Screening, Day 10 | 
| Safety and Tolerability: blood test results - total bilirubin | Total bilirubin in blood serum, umol/L | Screening, Day 10 | 
| Safety and Tolerability: blood test results - total protein | Total protein in blood serum, g/L | Screening, Day 10 | 
| Safety and Tolerability: blood test results - creatinine | Creatinine in blood serum, umol/L | Screening, Day 10 | 
| Safety and Tolerability: blood test results - urea | Urea in blood serum, mmol/L | Screening, Day 10 | 
| Safety and Tolerability: blood test results - aspartate transaminase (AST) | AST in blood serum, U/L | Screening, Day 10 | 
| Safety and Tolerability: blood test results - alanine transaminase (ALT) | ALT in blood serum, U/L | Screening, Day 10 | 
| Safety and Tolerability: blood test results - alkaline phosphatase (ALP) | ALP in blood serum, U/L | Screening, Day 10 | 
| Safety and Tolerability: urinalysis - specific gravity | Specific gravity of the urine | Screening, Day 10 | 
| Safety and Tolerability: urinalysis - color | Color of the urine, visual assessment (pale yellow, yellow, amder, brown etc.) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis - transparency | Transparency of the urine, visual assessment (transparent or cloudy) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis - pH | pH of the urine | Screening, Day 10 | 
| Safety and Tolerability: urinalysis - protein | Protein in the urine (g/L) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis - glucose | Glucose in the urine (mmol/L) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis (microscopy) - red blood cells | Red blood cells in the urine (number in sight) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis (microscopy) - white blood cells | White blood cells in the urine (number in sight) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis (microscopy) - epithelial cells | Epithelial cells in the urine (number in sight) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis (microscopy) - cylinders | Cylinders in the urine (number in sight) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis (microscopy) - bacteria | Bacteria in the urine (number in sight) | Screening, Day 10 | 
| Safety and Tolerability: urinalysis (microscopy) - mucus | Presence of mucus in the urine | Screening, Day 10 | 
| Safety and Tolerability: adverse event (AE) rate | Number and frequency of adverse events (AEs) or serious AEs (SAEs) | From the date of screening (and signing informed consent form) to the end of the study (Day 17) | 
| Safety and Tolerability: local reactions | Local reactions at the site of application will be evaluated separately on a 4-point scale (0 - no local reaction, 1 - weak local reaction in a limited area at the site of application, 2 - moderate local reaction in a limited/all area of application, 3 - strong local reaction in the whole area of application or going beyond it) | From the date of screening (and signing informed consent form) to the end of the study (Day 17) |