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

Official title

An Open-label 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

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.

Interventions

• Drug 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
  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
• Drug 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
  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
• Drug 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
  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

Primary outcome measures

• Pharmacokinetics - Cmax [Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)]
• Pharmacokinetics - tmax [Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)]
• Pharmacokinetics - AUC0-t [Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)]
• Pharmacokinetics - 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 [Time frame: From 0 hours extrapolated to infinity after single dose and from 48 hours extrapolated to infinity after multiple dose]
• Pharmacokinetics - t1/2 [Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)]
• Pharmacokinetics - kel [Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)]
• Pharmacokinetics - MRT [Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)]
• Pharmacokinetics - Vd [Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)]
• Pharmacokinetics - CL [Time frame: From 0 to 24 hours (single dose); from 48 to 72 hours (multiple dose)]

Secondary outcome measures (12)

• Adverse event type [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 [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 [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 [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 [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 [Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)]
• Safety and Tolerability: physical examination results - respiratory system [Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)]
• Safety and Tolerability: physical examination results - digestive tract [Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)]
• Safety and Tolerability: physical examination results - endocrine system [Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)]
• Safety and Tolerability: physical examination results - musculoskeletal system [Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)]
• Safety and Tolerability: physical examination results - nervous system [Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)]
• Safety and Tolerability: physical examination results - sensory systems [Time frame: Screening, Day 1 and 2 (single dosing), Day 1 to 4, 11 (multiple dosing)]

Eligibility criteria

Inclusion criteria

• Signed informed consent form by the healthy subject prior to any study activities.
• Males and females aged 18 to 45 years (inclusive) of Caucasian race.
• Verified "healthy" diagnosis (no abnormalities detected based on clinical, laboratory, and instrumental examination methods specified in the protocol).
• 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).
• Heart rate (HR) from 60 to 89 beats per minute (inclusive).
• Respiratory rate (RR) from 12 to 20 breaths per minute (inclusive).
• Body temperature from 36.0°C to 36.9°C (inclusive).
• 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.
• 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:

• Known allergic history.
• 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.
• 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.
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
• 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.
• History of GIT surgery (except for appendectomy at least 1 year prior to screening).
• Diseases/conditions that, in the judgment of the investigator, may affect the absorption, distribution, metabolism, or excretion of the study drug (SD).
• Acute infectious diseases less than 4 weeks before screening.
• 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.
• 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).
• Blood or plasma donation within 3 months before screening.
• Use of hormonal contraceptives (in women) within 2 months before the start of screening.
• Use of depot injections of any drugs less than 3 months before the start of screening.
• Pregnancy or lactation; positive urine pregnancy test for women of childbearing potential.
• Women of childbearing potential who have had unprotected sexual intercourse within 30 days prior to taking study medications with an unsterilized partner.
• Participation in another clinical trial less than 3 months prior to screening or concurrently with this study.
• 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.
• 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.
• Consumption of alcohol, caffeine, and xanthine-containing products within 7 days prior to taking the study drug.
• 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.
• Dehydration due to diarrhea, vomiting or other causes within the last 24 hours before taking the study drug.
• 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.
• 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.
• Information on risk factors for developing torsades de pointes such as heart failure, hypokalemia, family history of prolonged QT syndrome.
• Positive urine test for narcotic substances and potent medications at screening.
• Positive test for alcohol vapors at screening.
• Planning hospitalization during the study period for any reason other than hospitalization provided for by this protocol.
• Inability or unwillingness to comply with protocol requirements, perform procedures prescribed by the protocol, adhere to dietary and activity regimens.
• 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.
• 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

• The volunteer's withdrawal from further participation in the study.
• 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.).
• The emergence of reasons/situations during the study that threaten the safety of the volunteer (e.g., hypersensitivity reactions, etc.).
• Volunteers selected for participation in the study who do not meet inclusion/exclusion criteria.
• Development of a severe adverse event (SAE) and/or serious adverse reaction (SAR) in the volunteer during the study.
• The volunteer requires or undergoes treatment that may affect the pharmacokinetics of the study drug.
• Missing two or more consecutive blood samples or three or more blood samples during one study period.
• The occurrence of vomiting/diarrhea within 8 hours after taking the study drug.
• Positive urine test for narcotic substances and potent medications.
• Positive test for alcohol vapors.
• Positive pregnancy test in female participants.
• The emergence of other reasons during the study that prevent the conduct of the study according to the protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Single blind

Primary purpose

Other

Study locations

Russia · 1 center

• State Budgetary Healthcare Institution of the City of Moscow "City Clinical Hospital No. 1 — Moscow

Identifiers

NCT: NCT06859333 · IFR-01-01-2024

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗