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
- Registration Number
- NCT05505097
- Lead Sponsor
- Valenta Pharm JSC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 16
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description BCDA-sequence Hydroxymethylquinoxalindioxyde Hydroxymethylquinoxalindioxyde administration in a sequence B-C-D-A during the corresponding study periods 1, 2, 3, and 4 ABCD-sequence Hydroxymethylquinoxalindioxyde Hydroxymethylquinoxalindioxyde administration in a sequence A-B-C-D during the corresponding study periods 1, 2, 3, and 4 DABC-sequence Hydroxymethylquinoxalindioxyde Hydroxymethylquinoxalindioxyde administration in a sequence D-A-B-C during the corresponding study periods 1, 2, 3, and 4 CDAB-sequence Hydroxymethylquinoxalindioxyde Hydroxymethylquinoxalindioxyde administration in a sequence C-D-A-B during the corresponding study periods 1, 2, 3, and 4
- Primary Outcome Measures
Name Time Method Pharmacokinetics - Cmax From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Maximum plasma concentration (Cmax) of Hydroxymethylquinoxalindioxyde (HMQD)
Pharmacokinetics - AUC0-t From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of HMQD
Pharmacokinetics - tmax From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Time to reach Cmax (tmax) of HMQD
Pharmacokinetics - MRT From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Mean residence time (MRT) of HMQD
Pharmacokinetics - tlag From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Time from administration to first accessible concentration of HMQD
Pharmacokinetics - AUC0-inf From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of HMQD
Pharmacokinetics - t1/2 From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Elimination half-life (t1/2) of HMQD
Pharmacokinetics - Vd From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Volume of distribution of HMQD
Pharmacokinetics - kel From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Elimination constant (kel) of HMQD
Pharmacokinetics - AUCextr From 0 to 16 hours after each drug application on day 1, 7, 14, and 21 of the study Extrapolated AUC of HMQD, defined as (AUC0-inf - AUC0-t)/AUC0-inf
- Secondary Outcome Measures
Name Time Method Safety and Tolerability: vital signs - body temperature 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 Body temperature, centigrade scale
Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval Screening and the end of the study or an early termination visit, whichever came first, within 43 days of study participation 12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: PQ interval (ms)
Safety and Tolerability: complete blood count - red blood cells 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 Red blood cells, 10\^6/uL
Safety and Tolerability: complete blood count - erythrocyte sedimentation rate 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 Erythrocyte sedimentation rate, mm per hour
Safety and Tolerability: complete blood count - 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 Lymphocytes, %
Safety and Tolerability: complete blood count - 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 Eosinophils, %
Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate Screening and the end of the study or an early termination visit, whichever came first, within 43 days of study participation 12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: heart rate (beats per minute)
Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex Screening and the end of the study or an early termination visit, whichever came first, within 43 days of study participation 12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: QRS complex (ms)
Safety and Tolerability: complete blood count - hemoglobin 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 Hemoglobin, g/dL
Safety and Tolerability: complete blood count - 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 Hematocrit, %
Safety and Tolerability: complete blood count - platelets 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 Platelets, 10\^3/uL
Safety and Tolerability: complete blood count - white blood cells 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 White blood cells, 10\^3/uL
Safety and Tolerability: vital signs - diastolic blood pressure (DBP) 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 DBP, mmHg
Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval (QTc) Screening and the end of the study or an early termination visit, whichever came first, within 43 days of study participation 12-lead ECG (I, II, III, aVR, aVL, aVF, V1-V6) taken while lying down: QTc (ms)
Safety and Tolerability: serious adverse event (AE) rate 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 Number and frequency of serious AEs (SAEs)
Safety and Tolerability: vital signs - respiratory rate (RR) 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 RR, breaths per minute
Safety and Tolerability: vital signs - heart rate (HR) 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 HR, beats per minute
Safety and Tolerability: adverse event (AE) rate 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 Number and frequency of adverse events (AEs) or serious AEs (SAEs)
Safety and Tolerability: vital signs - systolic blood pressure (SBP) 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 SBP, mmHg
Safety and Tolerability: physical examination results 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 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.
Safety and Tolerability: complete blood count - 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 Monocytes, %
Safety and Tolerability: complete blood count - 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 Basophils, %
Safety and Tolerability: complete blood count - neutrophils 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 Neutrophils, % (segmented and stab)
Safety and Tolerability: blood test results - total cholesterol 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 Total cholesterol in blood serum, mmol/L
Safety and Tolerability: blood test results - aspartate transaminase (AST) 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 AST in blood serum, U/L
Safety and Tolerability: blood test results - cortisol 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 Cortisol in blood serum, pmol/L
Safety and Tolerability: blood test results - glucose 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 Glucose in blood serum, mmol/L
Safety and Tolerability: blood test results - total bilirubin 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 Total bilirubin in blood serum, umol/L
Safety and Tolerability: blood test results - alanine transaminase (ALT) 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 ALT in blood serum, U/L
Safety and Tolerability: urinalysis - color 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 Color of the urine
Safety and Tolerability: urinalysis - transparency 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 Transparency of the urine
Safety and Tolerability: urinalysis - pH 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 pH of the urine
Safety and Tolerability: urinalysis - protein 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 Protein in the urine (g/L)
Safety and Tolerability: urinalysis (microscopy) - cylinders 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 Cylinders in the urine (number in sight)
Safety and Tolerability: urinalysis - specific gravity 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 Specific gravity of the urine
Safety and Tolerability: urinalysis - glucose 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 Glucose in the urine (mmol/L)
Safety and Tolerability: urinalysis (microscopy) - red blood cells 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 Red blood cells in the urine (number in sight)
Safety and Tolerability: urinalysis (microscopy) - epithelial cells 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 Epithelial cells in the urine (number in sight)
Safety and Tolerability: urinalysis (microscopy) - bacteria 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 Bacteria in the urine (number in sight)
Safety and Tolerability: blood test results - total protein 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 Total protein in blood serum, g/L
Safety and Tolerability: blood test results - creatinine 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 Creatinine in blood serum, umol/L
Safety and Tolerability: blood test results - alkaline phosphatase (ALP) 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 ALP in blood serum, U/L
Safety and Tolerability: blood test results - aldosterone 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 Aldosterone in blood serum, pmol/L
Safety and Tolerability: urinalysis (microscopy) - white blood cells 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 White blood cells in the urine (number in sight)
Safety and Tolerability: urinalysis (microscopy) - mucus 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 Presence of mucus in the urine
Trial Locations
- Locations (1)
Limited Liability Company "X7 Clinical Research"
🇷🇺Saint Petersburg, Russian Federation