Safety and Pharmacokinetics of Dioxidin, Solution for Topical and External Use, 0.25 mg/ml and Dioxidin, Solution for Infusion and External Use, 5 mg/ml in Healthy Volunteers

Open Randomized Comparative Crossover Study of the Safety and Pharmacokinetics of Dioxidin, Solution for Topical and External Use, 0.25 mg/ml and Dioxidin, Solution for Infusion and External Use, 5 mg/ml in Healthy Volunteers

The study aimed for:

1. To study the safety of the drug Dioxidin, solution for topical and external use;
2. To determine the concentrations of the active substance of the studied drugs Dioxidin, solution for topical and external use, and Dioxidin, solution for infusion and external use in discrete time intervals;
3. To study pharmacokinetics of the drug Dioxidin, solution for topical and external application;
4. To determine the absolute bioavailability of the drug Dioxidine, solution for topical and external use.

Study Overview

• Status: Completed
• Conditions: Infections
• Intervention / Treatment: Drug: Hydroxymethylquinoxalindioxyde

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 194156
    • Limited Liability Company "X7 Clinical Research"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Voluntary and handwritten informed consent form signed by a healthy volunteer to participate in the study before any of the study procedures
• Age from 18 to 45 years (inclusive)
• Verified diagnosis "healthy" by standard clinical, laboratory, instrumental methods of examination
• Blood pressure level: systolic from 100 to 130 mmHg, diastolic from 60 to 90 mmHg (inclusive)
• Heart rate 60 to 90 beats per minute (inclusive)
• Body mass index (BMI) is 18.5 ≤ BMI ≤ 30.0 kg/m², with a body weight of ≥55 kg for men and ≥45 kg for women
• Volunteers must behave appropriately, coherent speech must be observed
• For women of childbearing potential, negative pregnancy test; consent of volunteers to either abstain from sexual intercourse or use a dual barrier method of contraception for the duration of study participation, beginning with the Screening Period, and for 3 weeks after study termination
• Ability to follow the daily routine and dietary regimen of the study protocol
• Ability to attend all scheduled appointments and stay at the Research Center for all Study Periods

Exclusion Criteria:

• A history of allergic reactions
• A history of drug intolerance to the active and/or excipients in the study medications
• Inability to successfully perform oropharyngeal rinse test
• Any chronic illnesses
• History of gastrointestinal surgery (except appendectomy)
• Acute infectious diseases less than 4 weeks prior to screening
• Taking medications that significantly affect hemodynamics and medications that affect liver function (barbiturates, omeprazole, cimetidine, etc.) less than 2 months before screening
• Regularly taking medications less than 2 weeks before screening and taking a single medication 7 days before screening
• Donating blood (450 mL of blood or plasma or more) less than 3 months before screening
• For women, the last intake of oral contraceptives at least 2 months prior to screening
• Pregnant and lactating women, and women and men of childbearing age who cannot or do not abstain from sexual intercourse or use a dual barrier method of contraception for the duration of study participation, beginning with the Screening Period, and for 3 weeks after the study ends
• Participation in another clinical trial less than 3 months before screening or concurrently with this study
• Taking more than 10 units of alcohol (1 unit of alcohol is equivalent to 330 ml of beer, 150 ml of wine, or 40 ml of spirits) in the week in the last month before inclusion in the study or anamnestic evidence of alcoholism, drug abuse, or medication abuse
• Smoking more than 10 cigarettes per day currently, or a history of smoking this number of cigarettes in the 6 months prior to screening
• A positive blood test for HIV, syphilis, hepatitis B/C
• A positive urine test for narcotics and powerful drugs
• Positive breath alcohol test
• Positive COVID-19 test
• Scheduled inpatient hospitalization during the study for any reason other than hospitalization as required by this protocol
• Inability or inability to meet the requirements of the protocol, including for physical, mental or social reasons, in the opinion of the Researcher
• Work/study regimen that is likely to make it impossible for the volunteer to complete the study and/or comply with the schedule of procedures
• Other conditions that, in the opinion of the Researcher, prevent the inclusion of the volunteer in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: ABCD-sequence; Hydroxymethylquinoxalindioxyde administration in a sequence A-B-C-D during the corresponding study periods 1, 2, 3, and 4	Drug: Hydroxymethylquinoxalindioxyde; Dioxidin (Hydroxymethylquinoxalindioxyde), solution for topical and external use, 0.25 mg/ml, applied as: A - single rinsing of the oropharynx with 15.0 ml of the drug solution for at least 30 seconds B - single irrigation of the oropharynx by spraying the preparation 4 times with a spray nozzle C - irrigation of the skin on the back by spraying the preparation 4 times from a distance of 10 cm on 1% of the body surface using a spray nozzle and exposing the solution for 30 minutes or D - Dioxidin (Hydroxymethylquinoxalindioxyde), solution for infusion and external application, 5 mg/ml, single intravenous 5 mg/ml in 1 ml; Other Names: Dioxidin
Other: BCDA-sequence; Hydroxymethylquinoxalindioxyde administration in a sequence B-C-D-A during the corresponding study periods 1, 2, 3, and 4	Drug: Hydroxymethylquinoxalindioxyde; Dioxidin (Hydroxymethylquinoxalindioxyde), solution for topical and external use, 0.25 mg/ml, applied as: A - single rinsing of the oropharynx with 15.0 ml of the drug solution for at least 30 seconds B - single irrigation of the oropharynx by spraying the preparation 4 times with a spray nozzle C - irrigation of the skin on the back by spraying the preparation 4 times from a distance of 10 cm on 1% of the body surface using a spray nozzle and exposing the solution for 30 minutes or D - Dioxidin (Hydroxymethylquinoxalindioxyde), solution for infusion and external application, 5 mg/ml, single intravenous 5 mg/ml in 1 ml; Other Names: Dioxidin
Other: CDAB-sequence; Hydroxymethylquinoxalindioxyde administration in a sequence C-D-A-B during the corresponding study periods 1, 2, 3, and 4	Drug: Hydroxymethylquinoxalindioxyde; Dioxidin (Hydroxymethylquinoxalindioxyde), solution for topical and external use, 0.25 mg/ml, applied as: A - single rinsing of the oropharynx with 15.0 ml of the drug solution for at least 30 seconds B - single irrigation of the oropharynx by spraying the preparation 4 times with a spray nozzle C - irrigation of the skin on the back by spraying the preparation 4 times from a distance of 10 cm on 1% of the body surface using a spray nozzle and exposing the solution for 30 minutes or D - Dioxidin (Hydroxymethylquinoxalindioxyde), solution for infusion and external application, 5 mg/ml, single intravenous 5 mg/ml in 1 ml; Other Names: Dioxidin
Other: DABC-sequence; Hydroxymethylquinoxalindioxyde administration in a sequence D-A-B-C during the corresponding study periods 1, 2, 3, and 4	Drug: Hydroxymethylquinoxalindioxyde; Dioxidin (Hydroxymethylquinoxalindioxyde), solution for topical and external use, 0.25 mg/ml, applied as: A - single rinsing of the oropharynx with 15.0 ml of the drug solution for at least 30 seconds B - single irrigation of the oropharynx by spraying the preparation 4 times with a spray nozzle C - irrigation of the skin on the back by spraying the preparation 4 times from a distance of 10 cm on 1% of the body surface using a spray nozzle and exposing the solution for 30 minutes or D - Dioxidin (Hydroxymethylquinoxalindioxyde), solution for infusion and external application, 5 mg/ml, single intravenous 5 mg/ml in 1 ml; Other Names: Dioxidin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax	Maximum plasma concentration (Cmax) of Hydroxymethylquinoxalindioxyde (HMQD)	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - tmax	Time to reach Cmax (tmax) of HMQD	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - tlag	Time from administration to first accessible concentration of HMQD	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - Vd	Volume of distribution of HMQD	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - AUC0-t	Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of HMQD	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - AUC0-inf	Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of HMQD	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - AUCextr	Extrapolated AUC of HMQD, defined as (AUC0-inf - AUC0-t)/AUC0-inf	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - kel	Elimination constant (kel) of HMQD	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - t1/2	Elimination half-life (t1/2) of HMQD	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study
Pharmacokinetics - MRT	Mean residence time (MRT) of HMQD	From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 or to an early termination visit, whichever came first, assessed up to 43 days for each participant
Safety and Tolerability: serious adverse event (AE) rate	Number and frequency of serious AEs (SAEs)	From the date of screening (and signing informed consent form) to the end of the study or to an early termination visit, whichever came first, assessed up to 43 days for each participant
Safety and Tolerability: vital signs - systolic blood pressure (SBP)	SBP, mmHg	Screening, -10 h, -1 h, 2 h, 12, and 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: vital signs - diastolic blood pressure (DBP)	DBP, mmHg	Screening, -10 h, -1 h, 2 h, 12, and 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: vital signs - respiratory rate (RR)	RR, breaths per minute	Screening, -10 h, -1 h, 2 h, 12, and 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: vital signs - heart rate (HR)	HR, beats per minute	Screening, -10 h, -1 h, 2 h, 12, and 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: vital signs - body temperature	Body temperature, centigrade scale	Screening, -10 h, -1 h, 2 h, 12, and 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
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.	Screening, -10 h, -1 h, 2 h, and 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: heart rate (beats per minute)	Screening and the end of the study or an early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: PQ interval (ms)	Screening and the end of the study or an early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: QRS complex (ms)	Screening and the end of the study or an early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval (QTc)	12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: QTc (ms)	Screening and the end of the study or an early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - hemoglobin	Hemoglobin, g/dL	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - red blood cells	Red blood cells, 10^6/uL	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - hematocrit	Hematocrit, %	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - platelets	Platelets, 10^3/uL	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - white blood cells	White blood cells, 10^3/uL	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and at the end of the study or at early termination visit within the time frame of the study
Safety and Tolerability: complete blood count - erythrocyte sedimentation rate	Erythrocyte sedimentation rate, mm per hour	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - lymphocytes	Lymphocytes, %	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - eosinophils	Eosinophils, %	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - monocytes	Monocytes, %	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - basophils	Basophils, %	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: complete blood count - neutrophils	Neutrophils, % (segmented and stab)	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - glucose	Glucose in blood serum, mmol/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - total cholesterol	Total cholesterol in blood serum, mmol/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - total protein	Total protein in blood serum, g/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - total bilirubin	Total bilirubin in blood serum, umol/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - creatinine	Creatinine in blood serum, umol/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - alkaline phosphatase (ALP)	ALP in blood serum, U/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - alanine transaminase (ALT)	ALT in blood serum, U/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - aspartate transaminase (AST)	AST in blood serum, U/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - aldosterone	Aldosterone in blood serum, pmol/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: blood test results - cortisol	Cortisol in blood serum, pmol/L	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and at the end of the study or at early termination visit within the time frame of the study
Safety and Tolerability: urinalysis - specific gravity	Specific gravity of the urine	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis - color	Color of the urine	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis - transparency	Transparency of the urine	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis - pH	pH of the urine	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis - protein	Protein in the urine (g/L)	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis - glucose	Glucose in the urine (mmol/L)	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis (microscopy) - red blood cells	Red blood cells in the urine (number in sight)	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis (microscopy) - white blood cells	White blood cells in the urine (number in sight)	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis (microscopy) - epithelial cells	Epithelial cells in the urine (number in sight)	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis (microscopy) - cylinders	Cylinders in the urine (number in sight)	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis (microscopy) - bacteria	Bacteria in the urine (number in sight)	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation
Safety and Tolerability: urinalysis (microscopy) - mucus	Presence of mucus in the urine	Screening, 24 h after each drug application on day 1, 7, 14, and 21 of the study, and on the end-of-study visit or on the early termination visit, whichever came first, within 43 days of study participation

Collaborators and Investigators

• Sponsor: Valenta Pharm JSC

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2022
• Primary Completion (Actual): December 19, 2022
• Study Completion (Actual): December 19, 2022

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: August 15, 2022
• First Posted (Actual): August 17, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: DIO-01-04-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No