Safety, Tolerability, and Pharmacokinetic Profile of Grammidin With Anesthetic, a Metered Dose Topical Spray in Healthy Volunteers

An Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of the Drug Grammidin With Anesthetic, a Metered Dose Topical Spray Following Single Administration in Healthy Volunteers

This study aims to evaluate the safety, tolerability, and pharmacokinetic profile of the Grammidin with anesthetic, a metered dose topical spray, compared to Grammidin with anesthetic neo, lozenges following single administration in healthy volunteers.

Inclusion Criteria:

1. Voluntarily and personally signed informed consent form by a healthy volunteer obtained prior to the conduct of any study-related procedure;
2. Males and females aged 18 to 45 years (inclusive);
3. Verified healthy status as demonstrated by the absence of clinically significant abnormalities in medical history, physical examination, laboratory tests, and other diagnostic procedures specified in the protocol;
4. Blood pressure (BP) level: systolic blood pressure (SBP) from 99 to 129 mm Hg (inclusive), diastolic blood pressure (DBP) from 70 to 89 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) between 18.5 kg/m² and 30 kg/m², with a minimum body weight of ≥ 55 kg for men and ≥ 45 kg for women;
9. Consent to use adequate contraceptive methods throughout the study and for 30 days after its completion, with a negative urine pregnancy test result for women of childbearing potential.

Non-Inclusion Criteria:

1. Clinically significant allergic history;
2. Hypersensitivity to active and/or excipient substances in the investigational drug and comparator drug in the medical history;
3. Drug intolerance to active and/or excipient substances in the investigational drug and comparator drug in the medical history;
4. 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;
5. Erosive-ulcerative lesions of the oral mucosa (aphthous stomatitis, mechanical trauma due to dental diseases, herpes lesions, and any other condition resulting in compromised integrity of the oral mucosa);
6. Surgical interventions on the GIT in the medical history (except for appendectomy performed at least 1 year prior to screening);
7. Diseases/conditions that, in the investigator's judgment, may affect the absorption, distribution, metabolism, or excretion of the investigational drugs;
8. Acute infectious diseases less than 4 weeks before screening;
9. Use of medications (drugs) that significantly affect hemodynamics and drugs affecting liver function (barbiturates, omeprazole, cimetidine, etc.) less than 2 months before screening;
10. Regular use of medications less than 2 weeks before screening and single use of medications less than 7 days before screening (including over-the-counter medications, vitamins, dietary supplements, herbal medicines);
11. Blood or plasma donating within 3 months prior to screening;
12. Use of hormonal contraceptives (in women) within 2 months prior to screening;
13. Use of depot injections of any medications within 3 months prior to screening;
14. Pregnancy or lactation; positive urine pregnancy test result for women of childbearing potential;
15. Female subjects of childbearing potential who had unprotected sexual intercourse with an unsterilized male partner within 30 days prior to administration investigational drugs;
16. Participation in another clinical study within 3 months prior to screening or concurrently with this study;
17. Consumption of more than 10 alcohol units per week (1 unit of alcohol is equivalent to 500 ml of beer, 200 ml of wine, or 50 ml of strong alcoholic beverages) 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 smoking that amount in the past 6 months prior to screening; unwillingness to refrain from smoking during hospitalization;
19. Consumption of alcohol, caffeine, and xanthine-containing products within 7 days prior to taking investigational drugs;
20. Consumption of citrus fruits, cranberries, rose hips and products containing them, or preparations/products containing St. John's wort within 7 days prior to taking investigational drugs;
21. Dehydration due to diarrhea, vomiting, or other causes within the last 24 hours prior to taking investigational drugs;
22. Positive blood test for antibodies to human immunodeficiency virus (HIV) types 1 and 2, antibodies to Treponema pallidum antigens, hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus antigens during screening;
23. Positive rapid test for SARS-CoV-2 at screening;
24. ECG abnormalities in medical history and/or during screening;
25. Positive urine test for narcotic substances and potent medications during screening;
26. Positive breath alcohol test result during screening;
27. Planning hospitalization during the study period for any reason other than hospitalization specified in this protocol;
28. Inability or unwillingness to comply with protocol requirements, perform procedures prescribed by the protocol, or adhere to dietary and activity restrictions;
29. Membership in a vulnerable population? including but not limited to students of medical, pharmaceutical and dental educational institutions, junior staff of clinics and laboratories, employees of pharmaceutical companies, military personnel, prisoners, residents of care facillities, individuals with low income or unemployed, members of ethnic minorities, homeless persons, vagrants, refugees, individuals under guardianship or conservatorship, ndividuals unable to provide informed consent and law enforcement personnel;
30. Dental procedures performed within 3 weeks prior to screening;
31. Other conditions that in the judgment of the Investigator may prevent volunteer inclusion in the study or lead to premature withdrawal from the study including adherence to fasting or special diets (e.g., vegetarianism, veganism, salt restriction) or special lifestyles (night work, extreme physical exertion).

Exclusion Criteria:

1. Withdrawal of the volunteer from further participation in the study;
2. Non-compliance by the volunteer with the study participation rules (missed study procedures, self-administration of drugs prohibited in the study, violation of dietary and lifestyle restrictions, etc.);
3. 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) in the volunteer during the study;
6. The volunteer undergoes or requires treatment that may affect the pharmacokinetic parameters (PKP) of the investigational drugs;
7. Missed collection of 2 or more consecutive blood samples or 3 or more blood samples within one study period;
8. Occurrence of vomiting/diarrhea within 6 hours after taking the investigational drug;
9. Positive urine test for narcotic substances and potent medications;
10. Positive breath test for alcohol vapors;
11. Positive pregnancy test result in women;
12. Positive SARS-CoV-2 test result;
13. Emergence of other reasons during the study that prevent conducting the study according to the protocol.