Acute Respiratory Viral Infections, Influenza
Conditions
Brief summary
This study aims to evaluate the safety and pharmacokinetic profile of the active ingredients Ingavirin forte, capsules, 90 mg + 20 mg (Valenta Pharm JSC, Russia) relative to single-entity Drug Ingavirin, capsules, 90 mg following administration under fasting and fed conditions.
Interventions
DRUGIngavirin forte, capsules, 90 mg + 20 mg
Ingavirin forte containing 90 mg of imidazolylethanamide of pentanedioic acid and 20 mg of N,N'-bis-\[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl\] diamide of malonic acid (XC9)
DRUGIngavirin, capsules, 90 mg
Ingavirin containing 90 mg of imidazolylethanamide of pentanedioic acid
Sponsors
Valenta Pharm JSC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Voluntarily and personally signed Informed Consent Form (ICF) by a participant obtained prior to the conduct of any study-related procedure; 2. Males and females aged 18 to 45 years (inclusive); 3. Confirmed healthy status, defined as the absence of clinically significant abnormalities based on clinical evaluation, laboratory assessments, and diagnostic procedures as specified in the protocol; 4. Blood pressure (BP) level: systolic blood pressure (SBP) from 100 to 130 mmHg (inclusive), diastolic blood pressure (DBP) from 70 to 85 mmHg (inclusive); 5. Heart rate (HR) from 60 to 89 beats/min (inclusive); 6. Respiratory rate (RR) from 12 to 20 per minute (inclusive); 7. Body temperature from 36.0°C to 36.9°C (inclusive); 8. Body mass index (BMI) of 18.5 kg/m² ≤ BMI ≤ 30 kg/m², with body weight for men being ≥ 55 kg and for women ≥ 45 kg; 9. Agreement to use adequate methods of contraception throughout the study and for 30 days after its completion; for women of childbearing potential - a negative urine β-hCG test result; 10. Subjects must demonstrate appropriate behavior and coherent speech; 11. Ability to comply with the daily routine and diet prescribed by the study protocol. Noninclusion Criteria: 1. Clinically significant allergic history; 2. History of hypersensitivity to imidazolylethanamide of pentanedioic acid and N,N'-bis-\[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl\] diamide of malonic acid (XC9) and/or to the excipients contained in the investigational medicinal product; 3. History of drug intolerance to imidazolylethanamide of pentanedioic acid and N,N'-bis-\[2-(1,3-diazocyclopenta-2,4-dien-4-yl)ethyl\] diamide of malonic acid (XC9) and/or to the excipients contained in the investigational medicinal product; 4. Known galactose intolerance, lactase deficiency, or glucose-galactose malabsorption; 5. Chronic diseases of the kidneys, liver, gastrointestinal (GI) tract, cardiovascular, lymphatic, respiratory, nervous, endocrine, musculoskeletal, genitourinary, or immune systems, or of the skin, hematopoietic organs, or eyes; 6. History of gastrointestinal (GI) surgical procedures, with the exception of appendectomy performed at least 1 year prior to screening; 7. Diseases/conditions that, in the investigator's opinion, may affect the absorption, distribution, metabolism, or excretion of the investigational medicinal product (IMP); 8. Acute infectious diseases less than 4 weeks prior to screening; 9. Use of medicinal products (MPs) that have a pronounced effect on hemodynamics, MPs affecting liver function (barbiturates, omeprazole, cimetidine, etc.), MPs prolonging the QT interval (antipsychotics (haloperidol, quetiapine, olanzapine, risperidone, sulpiride), antidepressants (fluoxetine, sertraline), antiarrhythmics (amiodarone), antibiotics (clarithromycin, azithromycin, moxifloxacin, levofloxacin, ciprofloxacin), antifungals (fluconazole), diuretics (furosemide)) less than 2 months prior to screening; 10. Regular use of MPs less than 2 weeks prior to screening and single use of MPs less than 7 days prior to screening (including over-the-counter MPs, vitamins, dietary supplements, herbal medicinal products); 11. Donation of blood or plasma less than 3 months prior to screening; 12. Use of hormonal contraceptives by womeninitiated less than 2 months prior to the screening visit. 13. Use of depot injections of any MPs less than 3 months prior to the start of screening; 14. Pregnancy or breastfeeding; positive urine pregnancy test result for women of childbearing potential; 15. Women of childbearing potential with a history of unprotected sexual intercourse within 30 days prior to study drug administration with a non-sterilized partner; 16. Participation in another clinical trial within 3 months prior to screening or concurrently with the current study. 17. Consumption of more than 10 standard alcohol units per week during the month prior to study enrollment, (1 standard unit = 500 mL beer, 200 mL wine, or 50 mL of strong alcoholic beverages), or history of alcoholism, drug dependence, or substance abuse. 18. Currently smoking more than 10 cigarettes per day, or a history of smoking the specified number of cigarettes within the 6 months preceding screening; refusal to abstain from smoking while staying at the study center; 19. Consumption of alcohol, caffeine, and xanthine-containing products within 7 days prior to IMP administration; 20. Consumption of citrus fruits, cranberries, rose hips and products containing them, or St. John's wort-containing preparations or products within 7 days prior to IMP administration; 21. Dehydration due to diarrhea, vomiting, or other causes within the last 24 hours prior to IMP administration; 22. Positive blood test result for antibodies to human immunodeficiency virus (HIV) 1 and 2, antibodies to Treponema pallidum antigens, hepatitis B surface antigen (HBsAg), or antibodies to hepatitis C virus antigens at screening; 23. Clinically significant abnormalities on the electrocardiogram (ECG) in the medical history and/or at screening, including: QTcF interval (corrected by Fredericia) ≥430 ms in men and ≥450 ms in women; 24. History of risk factors for torsades de pointes, such as heart failure, hypokalemia, or family history of long QT syndrome; 25. Electrolyte imbalances (based on Na+, K+, Cl- levels at screening); 26. Positive urine test for narcotic substances and potent medicinal products at screening; 27. Positive breath alcohol test at screening; 28. Planned hospitalization during the study period for any reason other than hospitalization required by this protocol; 29. Inability or incapacity to comply with the protocol requirements, perform protocol-specified procedures, or adhere to the diet and activity restrictions; 30. Belonging to a vulnerable group of volunteers: students of higher and secondary medical, pharmaceutical, and dental educational institutions; subordinate clinical or laboratory staff; employees of pharmaceutical companies; military personnel and prisoners; residents of long-term care facilities; low-income and unemployed individuals; representatives of national minorities; homeless individuals; refugees; individuals under guardianship or trusteeship; persons incapable of providing informed consent; as well as law enforcement officers; 31. Any other condition which, in the Investigator's judgment, would preclude the subject's enrollment in the study or could lead to premature withdrawal, including adherence to fasting practices or special diets (e.g., vegetarian, vegan, sodium-restricted) or lifestyle factors (e.g., night shift work, extreme physical exertion).
Exclusion criteria
1. Subject's decision to discontinue participation in the study; 2. Subject non-compliance with protocol requirements, including but not limited to missed study procedures, unauthorized use of prohibited concomitant medications, or failure to adhere to protocol-defined dietary and lifestyle restrictions. 3. Occurrence of any medical condition or safety concern during study participation that could compromise subject safety (e.g., hypersensitivity reactions, etc.); 4. Subjects enrolled in the study despite not meeting eligibility criteria (inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics - Cmax | From 0 to 24 hours | 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. |
| Pharmacokinetics - tmax | From 0 to 24 hours | Time to reach Cmax (tmax) |
| Pharmacokinetics - AUC0-t | From 0 to 24 hours | Area under the plasma concentration-time curve from time 0 to t (AUC0-t) |
| Pharmacokinetics - AUC0-inf | From 0 to 24 hours | Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) |
| Pharmacokinetics - AUCextr | From 0 to 24 hours | Extrapolated AUC defined as (AUC0-inf - AUC0-t)/AUC0-inf |
| Pharmacokinetics - t1/2 | From 0 to 24 hours | Elimination half-life (t1/2) |
| Pharmacokinetics - kel | From 0 to 24 hours | Elimination constant (kel) |
| Pharmacokinetics - number of terminal timepoints | From 0 to 24 hours | Number of points in the terminal logarithmic phase used to estimate the terminal elimination rate constant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse event type | From Screening to Day 29 ± 1 | 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. |
| Adverse event number | From Screening to Day 29 ± 1 | Number of adverse events registered during the study |
| Adverse event severety | From Screening to Day 29 ± 1 | Severity of adverse events registered during the study, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) |
| Discontinuations due to adverse events related to the investigational product | From Screening to Day 29 ± 1 | Number of subjects who discontinued the study early due to adverse events (including serious adverse events) related to the investigational product |
| Safety and Tolerability: volunteer complaints | From Screening to Day 29 ± 1 | Description of any health-related complaints received from volunteer |
| Safety and Tolerability: physical examination results - cardiovascular system | From Screening to Day 23 | 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) |
| Safety and Tolerability: physical examination results - respiratory system | From Screening to Day 23 | 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) |
| Safety and Tolerability: physical examination results - digestive tract | From Screening to Day 23 | 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) |
| Safety and Tolerability: physical examination results - endocrine system | From Screening to Day 23 | 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) |
| Safety and Tolerability: physical examination results - musculoskeletal system | From Screening to Day 23 | 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) |
| Safety and Tolerability: physical examination results - nervous system | From Screening to Day 23 | 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) |
| Safety and Tolerability: physical examination results - sensory systems | From Screening to Day 23 | 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) |
| Safety and Tolerability: physical examination results - skin/visible mucous membranes | From Screening to Day 23 | 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) |
| Safety and Tolerability: vital signs - systolic blood pressure | From Screening to Day 23 | Systolic blood pressure (SBP, mmHg) |
| Safety and Tolerability: vital signs - diastolic blood pressure | From Screening to Day 23 | Diastolic blood pressure (DBP, mmHg) |
| Safety and Tolerability: vital signs - heart rate | From Screening to Day 23 | Heart rate (HR, bpm) |
| Safety and Tolerability: vital signs - body temperature (Celsius temperature scale) | From Screening to Day 23 | Body temperature (Celsius temperature scale) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate | From Screening to Day 23 | 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) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval | From Screening to Day 23 | 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) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex | From Screening to Day 23 | 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) |
| Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval | From Screening to Day 23 | 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) |
| Safety and Tolerability: clinical blood test - hemoglobin | From Screening to Day 23 | Hemoglobin (g/L) |
| Safety and Tolerability: clinical blood test - hematocrit | From Screening to Day 23 | Hematocrit (%) |
| Safety and Tolerability: clinical blood test - red blood cell count | From Screening to Day 23 | Red blood cell count (cells/L) |
| Safety and Tolerability: clinical blood test - platelet count | From Screening to Day 23 | Platelet count (cells/L) |
| Safety and Tolerability: clinical blood test - leukocyte count | From Screening to Day 23 | Leukocyte count (cells/L) |
| Safety and Tolerability: clinical blood test - erythrocyte sedimentation rate | From Screening to Day 23 | Erythrocyte sedimentation rate (mm/h) |
| Safety and Tolerability: clinical blood test - myelocytes | From Screening to Day 23 | Leukocyte formula (myelocytes, %) |
| Safety and Tolerability: clinical blood test - band neutrophils | From Screening to Day 23 | Leukocyte formula (band neutrophils, %) |
| Safety and Tolerability: clinical blood test - segmented neutrophils | From Screening to Day 23 | Leukocyte formula (segmented neutrophils, %) |
| Safety and Tolerability: clinical blood test - eosinophils | From Screening to Day 23 | Leukocyte formula (eosinophils, %) |
| Safety and Tolerability: clinical blood test - basophils | From Screening to Day 23 | Leukocyte formula (basophils, %) |
| Safety and Tolerability: clinical blood test - monocytes | From Screening to Day 23 | Leukocyte formula (monocytes, %) |
| Safety and Tolerability: clinical blood test - lymphocytes | From Screening to Day 23 | Leukocyte formula (lymphocytes, %) |
| Safety and Tolerability: urinalysis - specific gravity | From Screening to Day 23 | Specific gravity of the urine |
| Safety and Tolerability: urinalysis - color | From Screening to Day 23 | Color of the urine |
| Safety and Tolerability: urinalysis - transparency | From Screening to Day 23 | Transparency of the urine |
| Safety and Tolerability: urinalysis - pH | From Screening to Day 23 | pH of the urine |
| Safety and Tolerability: urinalysis - protein | From Screening to Day 23 | Protein concentration (g/L) |
| Safety and Tolerability: urinalysis - glucose | From Screening to Day 23 | Glucose concentration (mmol/L) |
| Safety and Tolerability: urinalysis - red blood cells | From Screening to Day 23 | Red blood cell content (number in sight) |
| Safety and Tolerability: urinalysis - white blood cells | From Screening to Day 23 | White blood cell content (number in sight) |
| Safety and Tolerability: urinalysis - epithelial cells | From Screening to Day 23 | Epithelial cell content (number in sight) |
| Safety and Tolerability: urinalysis - casts | From Screening to Day 23 | Presence of casts (Yes/No) |
| Safety and Tolerability: urinalysis - mucus | From Screening to Day 23 | Presence of mucus (Yes/No) |
| Safety and Tolerability: urinalysis - bacteria | From Screening to Day 23 | Presence of bacteria (Yes/No) |
| Safety and Tolerability: urinalysis (microscopy) | From Screening to Day 23 | Changes in urine sediment parameters (RBCs, WBCs, casts, crystals) as assessed by microscopy |
| Safety and Tolerability: blood chemistry - glucose | From Screening to Day 23 | Glucose concentration (mmol/L) |
| Safety and Tolerability: blood chemistry - cholesterol | From Screening to Day 23 | Total cholesterol concentration (mmol/L) |
| Safety and Tolerability: blood chemistry - protein | From Screening to Day 23 | Total protein concentration (g/L) |
| Safety and Tolerability: blood chemistry - bilirubin | From Screening to Day 23 | Total bilirubin concentration (micromol/L) |
| Safety and Tolerability: blood chemistry - creatinine | From Screening to Day 23 | Creatinine concentration (micromol/L) |
| Safety and Tolerability: blood chemistry - alkaline phosphatase | From Screening to Day 23 | Alkaline phosphatase activity (U/L) |
| Safety and Tolerability: blood chemistry - alanine transaminase | From Screening to Day 23 | Alanine transaminase activity (U/L) |
| Safety and Tolerability: blood chemistry - aspartate transaminase | From Screening to Day 23 | Aspartate transaminase activity (U/L) |
| Safety and Tolerability: blood chemistry - potassium concentration | From Screening to Day 23 | Potassium (mmol/L) |
| Safety and Tolerability: blood chemistry - sodium concentration | From Screening to Day 23 | Sodium concentration (mmol/L) |
| Safety and Tolerability: blood chemistry - chloride concentration | From Screening to Day 23 | Chloride concentration (mmol/L) |
| Safety and Tolerability: blood chemistry - GFR | From Screening to Day 23 | Glomerular filtration rate, GFR (mL/min/1,73 м²) |
Countries
Russia
Outcome results
None listed