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This is a Single Center, First-in-human Study of Safety, Tolerability, and Pharmacokinetic Profile of Ascending Single and Multiple Doses of Ingavirin Forte, Capsules in Healthy Volunteers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single and multiple doses, 90 mg + 5 mg | Experimental | Ingavirin Forte, 1 capsule (90 mg + 5 mg) taken once under fasted conditions, followed by Ingavirin Forte, 1 capsule (90 mg + 5 mg) taken twice a day for 2 days (the first dose under fasted conditions, the second dose under fed conditions - 2 hours after a meal), and once in the morning under fasted conditions on the 3rd day. Wash-out period after a single-dose period will last from 7 to 21 days. |
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| Single and multiple doses, 90 mg + 10 mg | Experimental | Ingavirin Forte, 1 capsule (90 mg + 10 mg) taken once under fasted conditions, followed by Ingavirin Forte, 1 capsule (90 mg + 10 mg) taken twice a day for 2 days (the first dose on an under fasted conditions, the second dose under fed conditions - 2 hours after a meal), and once in the morning under fasted conditions on the 3rd day. Wash-out period after a single-dose period will last from 7 to 21 days. |
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| Single and multiple doses, 90 mg + 20 mg | Experimental | Ingavirin Forte, 1 capsule (90 mg + 20 mg) taken once under fasted conditions, followed by Ingavirin Forte, 1 capsule (90 mg + 20 mg) taken twice a day for 2 days (the first dose under fasted conditions, the second dose under fed conditions - 2 hours after a meal), and once in the morning under fasted conditions on the 3rd day. Wash-out period after a single-dose period will last from 7 to 21 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Combined preparation of imidazolylethylamide of pentanedioic acid and N,N'-bis-[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl] diamide of malonic acid, 90 mg + 5 mg | Drug | Capsules, containing 90 mg of imidazolylethylamide of pentanedioic acid and 5 mg of N,N'-bis-[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl] diamide of malonic acid |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics - Cmax | Maximum plasma concentration (Cmax) of imidazolylethylamide of pentanedioic acid and N,N'-bis-[2-(1,3-diazocyclopent-2,4-dien-4-yl)ethyl] diamide of malonic acid. The same analytes would be used for other pharmacokinetic measures listed below. | From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - tmax | Time to reach Cmax (tmax) | From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - AUC0-t | Area under the plasma concentration-time curve from time 0 to t (AUC0-t) | From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - AUC0-inf | Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) | From 0 hours extrapolated to infinity after single dose and from 48 hours extrapolated to infinity after multiple dose |
| Pharmacokinetics - AUCextr | Extrapolated AUC defined as (AUC0-inf - AUC0-t)/AUC0-inf | From 0 hours extrapolated to infinity after single dose and from 48 hours extrapolated to infinity after multiple dose |
| Pharmacokinetics - t1/2 | Elimination half-life (t1/2) | From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - kel |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse event type | Adverse events will be assessed by complaints, results of physical examination, results of heart rate and blood pressure assessment, results of respiratory rate assessment, body temperature, laboratory monitoring (clinical blood count, biochemical blood count, urinalysis), electrocardiography; adverse events will be classified in accordance to MedDRA. | From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period) |
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Inclusion Criteria:
Non-inclusion criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| State Budgetary Healthcare Institution of the City of Moscow "City Clinical Hospital No. 15 named after O.M. Filatov of the Department of Health of Moscow." | Recruiting | Moscow | Russia |
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|
| Combined preparation of imidazolylethylamide of pentanedioic acid and N,N'-bis-[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl] diamide of malonic acid, 90 mg + 10 mg | Drug | Capsules, containing 90 mg of imidazolylethylamide of pentanedioic acid and 10 mg of N,N'-bis-[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl] diamide of malonic acid |
|
| Combined preparation of imidazolylethylamide of pentanedioic acid and N,N'-bis-[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl] diamide of malonic acid, 90 mg + 20 mg | Drug | Capsules, containing 90 mg of imidazolylethylamide of pentanedioic acid and 20 mg of N,N'-bis-[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl] diamide of malonic acid |
|
Elimination constant (kel)
| From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - MRT | Mean residence time (MRT) | From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - Vd | Volume of distribution | From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - CL | Clearance (CL) | From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - number of terminal timepoints | Number of points in the terminal logarithmic phase used to estimate the terminal elimination rate constant | From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose) |
| Pharmacokinetics - AUC0-tau | Steady state area under the plasma concentration-time curve from time 0 to t (AUC0-tau) | From 0 to 48 hours (multiple dose) |
| Pharmacokinetics - Cmax,ss | Steady state maximum plasma concentration (Cmax,ss) | From 0 to 48 hours (multiple dose) |
| Pharmacokinetics - tmax,ss | Steady state time to reach Cmax,ss (tmax,ss) | From 0 to 48 hours (multiple dose) |
| Pharmacokinetics, urine - Aeinterval | The amount of active substance excreted in urine during each time interval (Aeinterval), calculated as the concentration in urine multiplied by the volume of urine. | From 48 to 72 hours (multiple dose) |
| Pharmacokinetics, urine - Ae(0-t) | Total urinary excretion from zero to time t (Ae(0-t)), calculated as the sum of the amounts excreted during each time interval | From 48 to 72 hours (multiple dose) |
| Pharmacokinetics, urine - Rmax | Maximum rate of urinary excretion (Rmax), calculated by dividing the amount of active substance excreted during each time interval by the time over which it was collected | From 48 to 72 hours (multiple dose) |
| Pharmacokinetics, urine - TRmax | Time of maximum urinary excretion (TRmax), calculated as the average time interval during which Rmax was observed | From 48 to 72 hours (multiple dose) |
| Pharmacokinetics, urine - Fe0-t | Fraction (% of dose) excreted from the body unchanged (Fe0-t), calculated as Ae/orally administered dose | From 48 to 72 hours (multiple dose) |
| Pharmacokinetics, urine - CLR | Renal clearance (CLR), calculated as the ratio of Ae(0-t) to AUC(0-t) | From 48 to 72 hours (multiple dose) |
| Adverse event number | Number of adverse events registered during the study | From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period) |
| Adverse event severety | Severity of adverse events registered during the study | From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period) |
| Drop-outs associated with adverse events | The number of cases of early termination of participation in the study due to the development of adverse events and/or serious adverse events associated with the study drug | From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period) |
| Safety and Tolerability: volunteer complaints | Description of any health-related complaints received from volunteer | From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period) |
| Safety and Tolerability: physical examination results - cardiovascular system | An assessment of the condition of the cardiovascular system and associated symptoms on physical examination (normal condition or a description of abnormal conditions/cardiovascular symptoms, if any) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: physical examination results - respiratory system | An assessment of the condition of the respiratory system and associated symptoms on physical examination (normal condition or a description of abnormal conditions/respiratory symptoms, if any) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: physical examination results - digestive tract | An assessment of the condition of the digestive tract and associated symptoms on physical examination (normal condition or a description of abnormal conditions/digestive tract symptoms, if any) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: physical examination results - endocrine system | An assessment of the condition of the endocrine system and associated symptoms on physical examination (normal condition or a description of abnormal conditions/endocrine symptoms, if any) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: physical examination results - musculoskeletal system | An assessment of the condition of the musculoskeletal system and associated symptoms on physical examination (normal condition or a description of abnormal conditions/musculoskeletal symptoms, if any) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: physical examination results - nervous system | An assessment of the condition of the nervous system and associated symptoms on physical examination (normal condition or a description of abnormal conditions/neurological symptoms, if any) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: physical examination results - sensory systems | An assessment of the condition of the sensory systems and associated symptoms on physical examination (normal condition or a description of abnormal conditions/symptoms, if any | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: physical examination results - skin/visible mucous membranes | An assessment of the condition of the skin/visible mucous membranes and associated symptoms on physical examination (normal condition or a description of abnormal conditions/symptoms, if any) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: vital signs - systolic blood pressure | Systolic blood pressure (SBP, mmHg) | Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: vital signs - diastolic blood pressure | Diastolic blood pressure (DBP, mmHg) | Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: vital signs - heart rate | Heart rate (HR, bpm) | Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: vital signs - body temperature (Celsius temperature scale) | Body temperature (Celsius temperature scale) | Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: heart rate (beats per minute) | Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: PQ interval (is the period, measured in milliseconds, that extends from the beginning of the P wave (the onset of atrial depolarization) until the beginning of the QRS complex) | Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: QRS complex (the QRS complex is the combination of three of the graphical deflections seen on a typical electrocardiogram) | Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval | 12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: corrected QT interval (distance from the beginning of the QRS complex to the end of the T wave; Fredericia correction) | Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - hemoglobin | Hemoglobin (g/L) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - hematocrit | Hematocrit (%) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - red blood cell count | Red blood cell count (cells/L) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - platelet count | Platelet count (cells/L) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - leukocyte count | Leukocyte count (cells/L) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - erythrocyte sedimentation rate | Erythrocyte sedimentation rate (mm/h) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - myelocytes | Leukocyte formula (myelocytes, %) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - band neutrophils | Leukocyte formula (band neutrophils, %) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - segmented neutrophils | Leukocyte formula (segmented neutrophils, %) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - eosinophils | Leukocyte formula (eosinophils, %) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - basophils | Leukocyte formula (basophils, %) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - monocytes | Leukocyte formula (monocytes, %) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: clinical blood test - lymphocytes | Leukocyte formula (lymphocytes, %) | Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - specific gravity | Specific gravity of the urine | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - color | Color of the urine | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - transparency | Transparency of the urine | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - pH | pH of the urine | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - protein | Protein concentration (g/L) | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - glucose | Glucose concentration (mmol/L) | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - red blood cells | Red blood cell content (number in sight) | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - white blood cells | White blood cell content (number in sight) | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - epithelial cells | Epithelial cell content (number in sight) | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - casts | Presence of casts (Yes/No) | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - mucus | Presence of mucus (Yes/No) | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis - bacteria | Presence of bacteria (Yes/No) | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: urinalysis (microscopy) | Microscopy of urine sediment is performed if it is present | Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - glucose | Glucose concentration (mmol/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - cholesterol | Total cholesterol concentration (mmol/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - protein | Total protein concentration (g/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - bilirubin | Total bilirubin concentration (micromol/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - creatinine | Creatinine concentration (micromol/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - alkaline phosphatase | Alkaline phosphatase activity (U/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - alanine transaminase | Alanine transaminase activity (U/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - aspartate transaminase | Aspartate transaminase activity (U/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - potassium concentration | Potassium (mmol/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - sodium concentration | Sodium concentration (mmol/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
| Safety and Tolerability: blood chemistry - chloride concentration | Chloride concentration (mmol/L) | Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing) |
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| ID | Term |
|---|---|
| D007251 | Influenza, Human |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D009976 | Orthomyxoviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012140 | Respiratory Tract Diseases |
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