Safety and Pharmacokinetics of Ingavirin Forte, Capsules, 90 mg + 20 mg (Valenta Pharm JSC, Russia) Compared With Ingavirin, Capsules, 90 mg, Under Fasting and Fed Conditions.

Official title

An Open-Label, Randomized, Crossover Clinical Study to Evaluate the Safety and Pharmacokinetics of the Active Ingredients of Ingavirin Forte, Capsules, 90 mg + 20 mg (Valenta Pharm JSC, Russia) Fixed-Dose Combination Compared With Single-Ingredient Drug Ingavirin, Capsules, 90 mg Under Fasting and Fed Conditions.

Overview

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

• Drug Ingavirin 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)
• Drug Ingavirin, capsules, 90 mg
  Ingavirin containing 90 mg of imidazolylethanamide of pentanedioic acid

Primary outcome measures

• Pharmacokinetics - Cmax [Time frame: From 0 to 24 hours]
• Pharmacokinetics - tmax [Time frame: From 0 to 24 hours]
• Pharmacokinetics - AUC0-t [Time frame: From 0 to 24 hours]
• Pharmacokinetics - AUC0-inf [Time frame: From 0 to 24 hours]
• Pharmacokinetics - AUCextr [Time frame: From 0 to 24 hours]
• Pharmacokinetics - t1/2 [Time frame: From 0 to 24 hours]
• Pharmacokinetics - kel [Time frame: From 0 to 24 hours]
• Pharmacokinetics - number of terminal timepoints [Time frame: From 0 to 24 hours]

Secondary outcome measures (12)

• Adverse event type [Time frame: From Screening to Day 29 ± 1]
• Adverse event number [Time frame: From Screening to Day 29 ± 1]
• Adverse event severety [Time frame: From Screening to Day 29 ± 1]
• Discontinuations due to adverse events related to the investigational product [Time frame: From Screening to Day 29 ± 1]
• Safety and Tolerability: volunteer complaints [Time frame: From Screening to Day 29 ± 1]
• Safety and Tolerability: physical examination results - cardiovascular system [Time frame: From Screening to Day 23]
• Safety and Tolerability: physical examination results - respiratory system [Time frame: From Screening to Day 23]
• Safety and Tolerability: physical examination results - digestive tract [Time frame: From Screening to Day 23]
• Safety and Tolerability: physical examination results - endocrine system [Time frame: From Screening to Day 23]
• Safety and Tolerability: physical examination results - musculoskeletal system [Time frame: From Screening to Day 23]
• Safety and Tolerability: physical examination results - nervous system [Time frame: From Screening to Day 23]
• Safety and Tolerability: physical examination results - sensory systems [Time frame: From Screening to Day 23]

Eligibility criteria

Inclusion criteria

• Voluntarily and personally signed Informed Consent Form (ICF) by a participant obtained prior to the conduct of any study-related procedure;
• Males and females aged 18 to 45 years (inclusive);
• 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;
• Blood pressure (BP) level: systolic blood pressure (SBP) from 100 to 130 mmHg (inclusive), diastolic blood pressure (DBP) from 70 to 85 mmHg (inclusive);
• Heart rate (HR) from 60 to 89 beats/min (inclusive);
• Respiratory rate (RR) from 12 to 20 per minute (inclusive);
• Body temperature from 36.0°C to 36.9°C (inclusive);
• 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;
• 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;
• Subjects must demonstrate appropriate behavior and coherent speech;
• Ability to comply with the daily routine and diet prescribed by the study protocol.

Noninclusion Criteria:

• Clinically significant allergic history;
• 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;
• 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;
• Known galactose intolerance, lactase deficiency, or glucose-galactose malabsorption;
• 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;
• History of gastrointestinal (GI) surgical procedures, with the exception of appendectomy performed at least 1 year prior to screening;
• Diseases/conditions that, in the investigator's opinion, may affect the absorption, distribution, metabolism, or excretion of the investigational medicinal product (IMP);
• Acute infectious diseases less than 4 weeks prior to screening;
• 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;
• 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);
• Donation of blood or plasma less than 3 months prior to screening;
• Use of hormonal contraceptives by womeninitiated less than 2 months prior to the screening visit.
• Use of depot injections of any MPs less than 3 months prior to the start of screening;
• Pregnancy or breastfeeding; positive urine pregnancy test result for women of childbearing potential;
• Women of childbearing potential with a history of unprotected sexual intercourse within 30 days prior to study drug administration with a non-sterilized partner;
• Participation in another clinical trial within 3 months prior to screening or concurrently with the current study.
• 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.
• 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;
• Consumption of alcohol, caffeine, and xanthine-containing products within 7 days prior to IMP administration;
• 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;
• Dehydration due to diarrhea, vomiting, or other causes within the last 24 hours prior to IMP administration;
• 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;
• 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;
• History of risk factors for torsades de pointes, such as heart failure, hypokalemia, or family history of long QT syndrome;
• Electrolyte imbalances (based on Na+, K+, Cl- levels at screening);
• Positive urine test for narcotic substances and potent medicinal products at screening;
• Positive breath alcohol test at screening;
• Planned hospitalization during the study period for any reason other than hospitalization required by this protocol;
• Inability or incapacity to comply with the protocol requirements, perform protocol-specified procedures, or adhere to the diet and activity restrictions;
• 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;
• 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

• Subject's decision to discontinue participation in the study;
• 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.
• Occurrence of any medical condition or safety concern during study participation that could compromise subject safety (e.g., hypersensitivity reactions, etc.);
• Subjects enrolled in the study despite not meeting eligibility criteria (inclusion/exclusion criteria violations).
• Prolongation of the QTcF interval on ECG recording (>500 ms or >60 ms compared to baseline measured on Days 1, 8, 15, and 22);
• Occurrence of a severe adverse event (AE) and/or serious adverse event (SAE) during study participation
• Missed collection of two or more consecutive blood samples for pharmacokinetic analysis or three or more samples within one pharmacokinetic study period;
• The volunteer is receiving or requires treatment that may affect the pharmacokinetic parameters of the study drug;
• Occurrence of vomiting/diarrhea within 8 hours after administration of the study drug;
• Positive urine test for narcotic substances and potent medicinal products;
• Positive breath alcohol test;
• Positive urine β-hCG test result in women;
• Emergence of any other reason during study participation that, in the Investigator's judgment, precludes the subject's continued compliance with protocol requirements.

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

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Other

Study locations

Russia · 1 center

• Federal Budgetary Institution of Science "North-West Public Health Research Center" — Saint Petersburg

Identifiers

NCT: NCT07645534 · IFR-01-02-2025

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗