Clinical trial NCT06859333: Safety, Tolerability, and Pharmacokinetic Parameters of Increasing Doses of Ingavirin Forte, Capsules, During Single and Subsequent Multiple Oral Administration in Healthy Volunteers
Official title: An Open Study on the Safety, Tolerability, and Pharmacokinetic Parameters of Increasing Doses of the Drug Ingavirin Forte, Capsules, During Single and Subsequent Multiple Oral Administration in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Influenza
Viral Respiratory Infection
Lead sponsor: Valenta Pharm JSC
Sponsor class: INDUSTRY
First posted: 2025-03-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

Brief summary: The study of safety, tolerability, and pharmacokinetic parameters of various doses of the drug Ingavirin Forte, capsules, in healthy volunteers.


Eligibility criteria: Inclusion Criteria:

1. A voluntarily and personally signed informed consent form by a healthy volunteer to participate in the study prior to any study procedures being conducted.
2. Men and women aged 18 to 45 years (inclusive) of Caucasian race.
3. Verified diagnosis of "healthy" (absence of deviations based on clinical, laboratory, and instrumental examination methods specified in the protocol).
4. Blood pressure (BP) levels: systolic blood pressure (SBP) from 100 to 130 mm Hg (inclusive), diastolic blood pressure (DBP) from 70 to 85 mm Hg (inclusive).
5. Heart rate (HR) from 60 to 89 beats per minute (inclusive).
6. Respiratory rate (RR) from 12 to 20 breaths per minute (inclusive).
7. Body temperature from 36.0°C to 36.9°C (inclusive).
8. Body mass index (BMI): 18.5 kg/m² ≤ BMI ≤ 30 kg/m², with a minimum body weight of ≥ 55 kg for men and ≥ 45 kg for women.
9. Agreement to use adequate contraceptive methods throughout the study and for 30 days after its completion; for women with preserved reproductive potential, a negative result on a urine pregnancy test is required.

Non-inclusion criteria:

1. Allergic history.
2. Hypersensitivity to imidazolylethylamide of pentanedioic acid and N,N'-bis-\[2-(1,3-diazocyclopent-2,4-dien-4-yl)ethyl\] diamide of malonic acid (XC9) and/or excipients included in the study drug in the medical history.
3. Drug intolerance to imidazolylethylamide of pentanedioic acid and N,N'-bis-\[2-(1,3-diazocyclopent-2,4-dien-4-yl)ethyl\] diamide of malonic acid (XC9) and/or excipients included in the study drug in the medical history.
4. Hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption in the medical history.
5. Chronic diseases of the kidneys, liver, gastrointestinal tract (GIT), cardiovascular, lymphatic, respiratory, nervous, endocrine, musculoskeletal, urogenital, and immune systems, as well as skin, hematopoietic organs, and the eye.
6. Surgical interventions on the GIT in the medical history (except for appendectomy 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 study drug (SD).
8. Acute infectious diseases less than 4 weeks before screening.
9. Use of drugs that significantly affect hemodynamics, drugs affecting liver function (barbiturates, omeprazole, cimetidine, etc.), drugs that prolong 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 before screening.
10. Regular use of drugs less than 2 weeks before screening and single use of drugs less than 7 days before screening (including over-the-counter drugs, vitamins, dietary supplements, herbal medicines).
11. Donating blood or plasma less than 3 months before screening.
12. Use of hormonal contraceptives (in women) less than 2 months before the start of screening.
13. Use of depot injections of any drugs less than 3 months before the start of screening.
14. Pregnancy or lactation; positive urine pregnancy test result for women with preserved reproductive potential.
15. Women with preserved reproductive potential who have had unprotected sexual intercourse within 30 days prior to taking study medications with an unsterilized partner.
16. Participation in another clinical trial less than 3 months prior to screening or concurrently with this study.
17. Consumption of more than 10 units of alcohol per week in the last month before inclusion in the study or a history of alcoholism, drug addiction, or substance abuse.
18. Smoking more than 10 cigarettes per day currently or having smoked that amount in the past 6 months prior to screening; unwillingness to refrain from smoking during their stay at the research center.
19. Consumption of alcohol, caffeine, and xanthine-containing products within 7 days prior to taking the study drug.
20. Consumption of citrus fruits, cranberries, rose hips and products containing them, preparations or products containing St. John's wort within 7 days prior to taking the study drug.
21. Dehydration due to diarrhea, vomiting or other causes within the last 24 hours before taking the study drug.
22. Positive blood test results for antibodies to human immunodeficiency virus (HIV) types 1 and 2; antibodies to Treponema pallidum antigens; surface antigen of hepatitis B virus (HBsAg); antibodies to hepatitis C virus antigens at screening.
23. Clinically significant deviations on electrocardiogram (ECG) in medical history and/or at screening including: QTcF interval (corrected by Fredericia) ≥430 ms in men and ≥450 ms in women.
24. Information on risk factors for developing torsades de pointes such as heart failure, hypokalemia, family history of prolonged QT syndrome.
25. Positive urine test for narcotic substances and potent medications at screening.
26. Positive breath alcohol test at screening.
27. Planning hospitalization during the study period for any reason other than hospitalization provided for by this protocol.
28. Inability or unwillingness to comply with protocol requirements, perform procedures prescribed by the protocol, adhere to dietary and activity regimens.
29. Belonging to a vulnerable group of volunteers: students from higher and secondary medical, pharmaceutical and dental educational institutions; junior staff from clinics and laboratories; employees of pharmaceutical companies; military personnel and prisoners; individuals in nursing homes; low-income and unemployed individuals; representatives of national minorities; homeless individuals; refugees; individuals under guardianship or custody; individuals unable to give consent; as well as law enforcement officers.
30. Other conditions that in the investigator's opinion prevent volunteer inclusion in the study or may lead to early withdrawal from the study including adherence to fasting or special diets (e.g., vegetarianism, veganism, salt restriction) or a special lifestyle (night work hours, extreme physical exertion).

Exclusion Criteria:

1. The volunteer's withdrawal from further participation in the study.
2. Non-compliance by the volunteer with the study participation rules (missed study procedures, self-administration of prohibited medications, violation of dietary and lifestyle restrictions, etc.).
3. The emergence of reasons/situations during the study that threaten the safety of the volunteer (e.g., hypersensitivity reactions, etc.).
4. Volunteers selected for participation in the study who do not meet inclusion/exclusion criteria.
5. Development of a severe adverse event (SAE) and/or serious adverse reaction (SAR) in the volunteer during the study.
6. The volunteer requires or undergoes treatment that may affect the pharmacokinetics of the study drug.
7. Missing two or more consecutive blood samples or three or more blood samples during one study period.
8. The occurrence of vomiting/diarrhea within 8 hours after taking the study drug.
9. Positive urine test for narcotic substances and potent medications.
10. Positive breath alcohol test result.
11. Positive pregnancy test result in women.
12. The emergence of other reasons during the study that prevent the conduct of the study according to the protocol.

Primary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - tmax
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - AUC0-t
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - AUC0-inf
timeFrame: From 0 hours extrapolated to infinity after single dose and from 48 hours extrapolated to infinity after multiple dose
measure: Pharmacokinetics - AUCextr
timeFrame: From 0 hours extrapolated to infinity after single dose and from 48 hours extrapolated to infinity after multiple dose
measure: Pharmacokinetics - t1/2
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - kel
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - MRT
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - Vd
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - CL
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - number of terminal timepoints
timeFrame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)
measure: Pharmacokinetics - AUC0-tau
timeFrame: From 0 to 48 hours (multiple dose)
measure: Pharmacokinetics - Cmax,ss
timeFrame: From 0 to 48 hours (multiple dose)
measure: Pharmacokinetics - tmax,ss
timeFrame: From 0 to 48 hours (multiple dose)
measure: Pharmacokinetics, urine - Aeinterval
timeFrame: From 48 to 72 hours (multiple dose)
measure: Pharmacokinetics, urine - Ae(0-t)
timeFrame: From 48 to 72 hours (multiple dose)
measure: Pharmacokinetics, urine - Rmax
timeFrame: From 48 to 72 hours (multiple dose)
measure: Pharmacokinetics, urine - TRmax
timeFrame: From 48 to 72 hours (multiple dose)
measure: Pharmacokinetics, urine - Fe0-t
timeFrame: From 48 to 72 hours (multiple dose)
measure: Pharmacokinetics, urine - CLR
timeFrame: From 48 to 72 hours (multiple dose)
Secondary outcomes:
measure: Adverse event type
timeFrame: 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)
measure: Adverse event number
timeFrame: 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)
measure: Adverse event severety
timeFrame: 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)
measure: Drop-outs associated with adverse events
timeFrame: 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)
measure: Safety and Tolerability: volunteer complaints
timeFrame: 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)
measure: Safety and Tolerability: physical examination results - cardiovascular system
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: physical examination results - respiratory system
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: physical examination results - digestive tract
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: physical examination results - endocrine system
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: physical examination results - musculoskeletal system
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: physical examination results - nervous system
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: physical examination results - sensory systems
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: physical examination results - skin/visible mucous membranes
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: vital signs - systolic blood pressure
timeFrame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: vital signs - diastolic blood pressure
timeFrame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: vital signs - heart rate
timeFrame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: vital signs - body temperature (Celsius temperature scale)
timeFrame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate
timeFrame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - PQ interval
timeFrame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - QRS complex
timeFrame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: 12-lead electrocardiogram (ECG) - corrected QT interval
timeFrame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - hemoglobin
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - hematocrit
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - red blood cell count
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - platelet count
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - leukocyte count
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - erythrocyte sedimentation rate
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - myelocytes
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - band neutrophils
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - segmented neutrophils
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - eosinophils
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - basophils
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - monocytes
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: clinical blood test - lymphocytes
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - specific gravity
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - color
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - transparency
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - pH
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - protein
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - glucose
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - red blood cells
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - white blood cells
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - epithelial cells
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - casts
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - mucus
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis - bacteria
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: urinalysis (microscopy)
timeFrame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - glucose
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - cholesterol
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - protein
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - bilirubin
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - creatinine
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - alkaline phosphatase
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - alanine transaminase
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - aspartate transaminase
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - potassium concentration
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - sodium concentration
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
measure: Safety and Tolerability: blood chemistry - chloride concentration
timeFrame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: 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."
Study officials:
References: