Clinical trial NCT06859281: Safety, Tolerability, and Pharmacokinetic Parameters of Grammidin, a Metered Spray in Healthy Volunteers
Official title: An Open Study to Investigate the Safety, Tolerability, and Pharmacokinetic Parameters of the Drug Grammidin, a Metered Spray for Local Application Upon Single Use in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pharyngitis
Lead sponsor: Valenta Pharm JSC
Sponsor class: INDUSTRY
First posted: 2025-03-05
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Study of the safety, tolerability, and pharmacokinetic parameters of the investigational drug Grammidin, a metered spray for local application, compared to Grammidin lozenges upon single use in healthy volunteers.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily and personally signed informed consent form by a healthy volunteer to participate in the study before any study procedures are conducted;
2. Men and women aged 18 to 45 years (inclusive);
3. Verified diagnosis of "healthy" (absence of deviations based on clinical, laboratory, and instrumental examination methods 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 with preserved reproductive potential.

Non-Inclusion Criteria:

1. History of significant allergic reactions;
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 injuries due to dental diseases, herpes outbreaks, and any other diseases or conditions leading to disruption of the 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 opinion, 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. Donating blood or plasma less than 3 months before screening;
12. Use of hormonal contraceptives (in women) less than 2 months before screening;
13. Use of depot injections of any medications less than 3 months before screening;
14. Pregnancy or lactation; positive urine pregnancy test result for women with preserved reproductive potential;
15. Women with preserved reproductive potential who have had unprotected sexual contact within 30 days prior to taking investigational drugs with an unsterilized partner;
16. Participation in another clinical study less than 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 coronavirus disease 2019 (COVID-19) during 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. 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 provide consent as well as law enforcement personnel;
30. Dental procedures performed less than 3 weeks prior to screening;
31. Other conditions that in the opinion 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 COVID-19 test result;
13. Emergence of other reasons during the study that prevent conducting the study according to the protocol.

Primary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: From 0 to 24 hours after each drug intake.
measure: Pharmacokinetics - tmax
timeFrame: From 0 to 24 hours after each drug intake.
measure: Pharmacokinetics - AUC0-t
timeFrame: From 0 to 24 hours after each drug intake.
measure: Pharmacokinetics - AUC0-inf
timeFrame: From 0 hours after each drug intake (extrapolated to infinity).
measure: Pharmacokinetics - AUCextr
timeFrame: From 0 hours after each drug intake (extrapolated to infinity).
measure: Pharmacokinetics - t1/2
timeFrame: From 0 to 24 hours after each drug intake.
measure: Pharmacokinetics - kel
timeFrame: From 0 to 24 hours after each drug intake.
measure: Pharmacokinetics - MRT
timeFrame: From 0 to 24 hours after each drug intake.
measure: Pharmacokinetics - Vd
timeFrame: From 0 to 24 hours after each drug intake.
measure: Pharmacokinetics - CL
timeFrame: From 0 to 24 hours after each drug intake.
measure: Pharmacokinetics - number of terminal timepoints
timeFrame: From 0 to 24 hours after each drug intake.
Secondary outcomes:
measure: Adverse event type
timeFrame: From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
measure: Adverse event number
timeFrame: From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
measure: Adverse event severety
timeFrame: From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
measure: Drop-outs associated with adverse events
timeFrame: From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
measure: Volunteer complaints
timeFrame: From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
measure: Physical examination results - cardiovascular system
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Physical examination results - respiratory system
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Physical examination results - digestive tract
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Physical examination results - endocrine system
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Physical examination results - musculoskeletal system
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Safety and Tolerability: physical examination results - nervous system
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Physical examination results - sensory systems
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Physical examination results - skin/visible mucous membranes
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Vital signs - systolic blood pressure
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Vital signs - diastolic blood pressure
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Vital signs - heart rate
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: Vital signs - body temperature (Celsius temperature scale)
timeFrame: Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
measure: 12-lead electrocardiogram (ECG) - heart rate
timeFrame: Screeninig (days -14 to -1), day 1, 2, 8, 9, 15 ± 1
measure: 12-lead electrocardiogram (ECG) - PQ interval
timeFrame: Screeninig (days -14 to -1), day 1, 2, 8, 9, 15 ± 1
measure: 12-lead electrocardiogram (ECG) - QRS complex
timeFrame: Screeninig (days -14 to -1), day 1, 2, 8, 9, 15 ± 1
measure: 12-lead electrocardiogram (ECG) - corrected QT interval
timeFrame: Screeninig (days -14 to -1), day 1, 2, 8, 9, 15 ± 1
measure: Clinical blood test - hemoglobin
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - hematocrit
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - red blood cell count
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - platelet count
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - leukocyte count
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - erythrocyte sedimentation rate
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - myelocytes
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - band neutrophils
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - segmented neutrophils
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - eosinophils
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - basophils
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - monocytes
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Clinical blood test - lymphocytes
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - specific gravity
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - color
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - transparency
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - pH
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - protein
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - glucose
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - red blood cells
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - white blood cells
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - epithelial cells
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - casts
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - mucus
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis - bacteria
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Urinalysis (microscopy)
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Blood chemistry - glucose
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Blood chemistry - cholesterol
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Blood chemistry - protein
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Blood chemistry - bilirubin
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Blood chemistry - creatinine
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Blood chemistry - alkaline phosphatase
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Blood chemistry - alanine transaminase
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
measure: Blood chemistry - aspartate transaminase
timeFrame: Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Limited Liability Company "Research Center Eco-Safety"
Study officials:
References: