Food-Effect, Single and Multiple Dose Pharmacokinetics, Safety and Tolerability Study of 4-MUST, 128 mg, Tablets in Healthy Volunteers

An Open-Label Study to Evaluate the Effect of Food on the Bioavailability of 4-MUST, 128 mg, Tablets and to Assess the Pharmacokinetics, Safety, and Tolerability Following Single and Multiple Dose Administration in Healthy Volunteers

This open-label study will evaluate the effect of food on the bioavailability of a single dose of 4-MUST, tablets, 128 mg. Additionally, the study will assess the pharmacokinetics, safety, and tolerability of 4-MUST, tablets, 128 mg following both single and multiple oral dose administration.

Inclusion Criteria:

• Voluntary, personally signed ICF obtained prior to any study procedures;
• Males and females aged 18 to 45 years (inclusive) of Caucasian race;
• Confirmed healthy status based on the absence of clinically significant abnormalities in clinical, laboratory, and diagnostic assessments specified in the protocol;
• Blood pressure (BP): systolic blood pressure (SBP) from 99 to 129 mmHg (inclusive), diastolic blood pressure (DBP) from 70 to 89 mmHg (inclusive);
• Heart rate (HR) from 60 to 89 beats/min (inclusive);
• Respiratory rate (RR) from 12 to 20 per 1 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 ≥ 55 kg for males and ≥ 45 kg for females;
• Commitment to adhere to highly effective contraceptive methods during the study participation period and for 30 days thereafter; documentation of negative urine pregnancy test for women of childbearing potential.

Noninclusion Criteria:

• History of clinically significant allergic reactions;
• Hypersensitivity to hymecromone and trimebutine and/or excipients included in the study drug in anamnesis;
• Drug intolerance to hymecromone and trimebutine and/or excipients included in the study drug in the anamnesis;
• Hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption in the anamnesis;
• Chronic diseases of the kidney, liver, gastrointestinal tract (GIT), cardiovascular, lymphatic, respiratory, nervous, endocrine, musculoskeletal, genitourinary and immune systems, as well as skin, hematopoietic and visual organs;
• History of GI surgery (except for appendectomy at least 1 year prior to screening);
• Diseases/conditions that, in the opinion of the investigator, may affect the absorption, distribution, metabolism, or excretion of the study drug;
• Acute infectious diseases less than 4 weeks prior to screening;
• Intake of drugs that have a significant effect on hemodynamics and drugs that affect liver function (barbiturates, omeprazole, cimetidine, etc.) less than 2 months before screening;
• Regular intake of a medicine less than 2 weeks prior to screening and single intake of a medicine less than 7 days prior to screening (including over-the-counter medicines, vitamins, supplements, herbs);
• Blood or plasma donation less than 3 months prior to screening;
• Use of hormonal contraceptives (in women) less than 2 months prior to screening;
• Use of depot injections of any medicine less than 3 months prior to screening;
• Pregnancy or lactation period; positive pregnancy test for women of childbearing potential;
• Women of childbearing potential who have had unprotected sexual intercourse with a non-sterilized male partner within 30 days prior to administration of the study drug;
• Participation in another clinical trial less than 3 months prior to screening or concurrent with the present study;
• Consumption of more than 10 units of alcohol per week during the month prior to study enrollment (1 unit of alcohol is equivalent to 500 mL of beer, 200 mL of wine, or 50 mL of spirits), or a history of alcoholism, drug dependence, or abuse of medicinal products;
• Smoking more than 10 cigarettes per day currently, or a history of smoking the indicated number of cigarettes in the 6 months preceding screening; failure to agree to abstain from smoking for the duration of the hospital stay;
• Consumption of alcohol, caffeine, and xanthine-containing products in the 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 - 7 days before taking the study drug;
• Dehydration due to diarrhea, vomiting, or other cause within the last 24 hours prior to taking the study drug;
• Positive blood test result for antibodies to human immunodeficiency virus (HIV) 1 and 2, antibodies to Treponema pallidum antigens, hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus antigens at screening;
• Clinically significant abnormalities on electrocardiogram (ECG) in the medical history and/or at screening;
• Positive urinalysis for narcotics and potent drugs at screening;
• Positive breath alcohol vapor test at screening;
• Scheduling a hospital stay during the study period, for any reason other than hospitalization required by this protocol;
• Failure or inability to comply with protocol requirements, follow protocol procedures, diet and activity regimen.
• Belonging to a vulnerable population, including: students enrolled in medical, pharmaceutical, or dental educational institutions, clinical and laboratory assistants, pharmaceutical company employees, military personnel and prisoners, persons residing in residential care facilities, low-income and unemployed, minorities, homeless, vagrants, refugees, persons in foster care, persons unable to consent, and law enforcement officers;
• Any other condition that, in the judgement of the Investigator, would preclude the volunteer's enrollment in the study or could lead to premature withdrawal from the study, including adherence to fasting regimens or special diets (e.g., vegetarian, vegan, or sodium-restricted diets) or lifestyle factors (e.g., night-shift work or extreme physical exertion)

Exclusion criteria:

• Voluntary withdrawal of the subject from the study;
• Failure to comply with protocol requirements by the volunteer (e.g., missing scheduled study procedures, unauthorized use of prohibited medications, or violation of dietary or lifestyle restrictions);
• Occurrence of any event or condition during the study that, in the investigator's judgement, may compromise the volunteer's safety (e.g., hypersensitivity reactions);
• Volunteers selected for participation in the study in violation of the inclusion/non-inclusion criteria;
• Development of severe adverse event and/or a serious adverse event in a volunteer during the course of the study;
• Volunteer is receiving or requires treatment that may affect the pharmacokinetic parameters of the study drug;
• Missing collection of 2 or more consecutive blood samples or 3 x or more blood samples during the same Study Period;
• Occurrence of vomiting/diarrhea within 6 h after administration of study drug;
• Positive urine test for narcotics and potent drugs;
• Positive breath alcohol test;
• Positive pregnancy test in women;
• Occurrence of any other circumstance that precludes conduct of the study in accordance with the protocol.