Study of the Safety, Tolerability, and Pharmacokinetic Profile of Ascending Doses of Ingavirin Forte, Capsules, Folliwing Single and Subsequent Multiple Oral Administration in Healthy Volunteers

Phase 1RecruitingNCT06859333

Valenta Pharm JSC36 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

OTHER

Masking

SINGLE

Enrollment

Conditions

Influenza Viral Respiratory Infection

Interventions

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 mgDRUG

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

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 mgDRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Signed informed consent form by the healthy subject prior to any study activities. 2. Males and females aged 18 to 45 years (inclusive) of Caucasian race. 3. Verified "healthy" diagnosis (no abnormalities detected 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 of childbearing potential - a negative urine pregnancy test result. Non-inclusion criteria: 1. Known 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. 4. Lactose intolerance, lactase deficiency, glucose-galactose malabsorption. 5. Evidence or history of chronic diseases of the kidneys, liver, gastrointestinal tract (GIT), cardiovascular, lymphatic, respiratory, nervous, endocrine, musculoskeletal, urogenital, and immune systems, as well as skin, hematopoietic and vision organs. 6. History of GIT surgery (except for appendectomy at least 1 year prior to screening). 7. Diseases/conditions that, in the judgment of the investigator, 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. Blood or plasma donation within 3 months before screening. 12. Use of hormonal contraceptives (in women) within 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 for women of childbearing potential. 15. Women of childbearing 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 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 test for alcohol vapors 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 judgment of the investigator, may interfere with participation in the study or may lead to early withdrawal of the volunteer 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 test for alcohol vapors. 11. Positive pregnancy test in female participants. 12. The emergence of other reasons during the study that prevent the conduct of the study according to the protocol.

Locations (1)

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."

Moscow, Russia

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)

Pharmacokinetics - tmax

Time to reach Cmax (tmax)

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)

Pharmacokinetics - kel

Elimination constant (kel)

Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

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.

Time frame: 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 number

Number of adverse events registered during the study

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)

Safety and Tolerability: 12-lead electrocardiogram (ECG) - heart rate

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Screening, Day 1 to 2 (single dosing), Day 1 to 4, 11 (multiple dosing)

Safety and Tolerability: clinical blood test - hemoglobin

Hemoglobin (g/L)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)

Safety and Tolerability: clinical blood test - hematocrit

Hematocrit (%)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)

Safety and Tolerability: clinical blood test - myelocytes

Leukocyte formula (myelocytes, %)

Time frame: 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, %)

Time frame: 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, %)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)

Safety and Tolerability: clinical blood test - eosinophils

Leukocyte formula (eosinophils, %)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)

Safety and Tolerability: clinical blood test - basophils

Leukocyte formula (basophils, %)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)

Safety and Tolerability: clinical blood test - monocytes

Leukocyte formula (monocytes, %)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1, 3, 4, 11 (multiple dosing)

Safety and Tolerability: clinical blood test - lymphocytes

Leukocyte formula (lymphocytes, %)

Time frame: 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

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - color

Color of the urine

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - transparency

Transparency of the urine

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - pH

pH of the urine

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - protein

Protein concentration (g/L)

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - glucose

Glucose concentration (mmol/L)

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - red blood cells

Red blood cell content (number in sight)

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - white blood cells

White blood cell content (number in sight)

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - epithelial cells

Epithelial cell content (number in sight)

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - casts

Presence of casts (Yes/No)

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - mucus

Presence of mucus (Yes/No)

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: urinalysis - bacteria

Presence of bacteria (Yes/No)

Time frame: 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

Time frame: Screening, Day 2 (single dosing), Day 4, 11 (multiple dosing)

Safety and Tolerability: blood chemistry - glucose

Glucose concentration (mmol/L)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)

Safety and Tolerability: blood chemistry - creatinine

Creatinine concentration (micromol/L)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)

Safety and Tolerability: blood chemistry - potassium concentration

Potassium (mmol/L)

Time frame: 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)

Time frame: 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)

Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)