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

An Open-label Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of the Drug Grammidin, 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, a metered dose topical spray, compared to Grammidin lozenges following single administration in healthy volunteers .

Study Overview

• Status: Recruiting
• Conditions: Pharyngitis
• Intervention / Treatment: Drug: Grammidin neo; Drug: Grammidin, a metered dose topical spray

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Saint Petersburg, Russian Federation, 196143
    • Recruiting
    • Limited Liability Company "Research Center Eco-Safety"
    • Contact: Viktoria Dedkova, MD; Phone Number: +7-812-500-52-03; Email: dedkova_va@ecosafety.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RT sequence: Grammidin neo, lozenges, followed by Grammidin, a metered dose topical spray; RT sequence where R is Grammidin neo, lozenges and T is Grammidin, a metered dose topical spray	Drug: Grammidin neo; Grammidin neo, lozenges, 1 lozenge to be taken once under fed conditions.; Other Names: cetylpyridinium chloride; gramicidin s; Drug: Grammidin, a metered dose topical spray; Grammidin, a metered dose topical spray, 4 sprays to be taken once under fed conditions.; Other Names: cetylpyridinium chloride; gramicidin s
Experimental: TR sequence: Grammidin, a metered dose topical spray, followed by Grammidin neo, lozenges; TR sequence where T is Grammidin, a metered dose topical spray and R is Grammidin neo, lozenges	Drug: Grammidin neo; Grammidin neo, lozenges, 1 lozenge to be taken once under fed conditions.; Other Names: cetylpyridinium chloride; gramicidin s; Drug: Grammidin, a metered dose topical spray; Grammidin, a metered dose topical spray, 4 sprays to be taken once under fed conditions.; Other Names: cetylpyridinium chloride; gramicidin s

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics - Cmax	Maximum plasma concentration (Cmax) of gramicidin S and cetylpyridinium chloride. The same analytes would be used for other pharmacokinetic measures listed below.	From 0 to 24 hours after each drug intake.
Pharmacokinetics - tmax	Time to reach Cmax (tmax)	From 0 to 24 hours after each drug intake.
Pharmacokinetics - AUC0-t	Area under the plasma concentration-time curve from time 0 to t (AUC0-t)	From 0 to 24 hours after each drug intake.
Pharmacokinetics - AUC0-inf	Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)	From 0 hours after each drug intake (extrapolated to infinity).
Pharmacokinetics - AUCextr	Extrapolated AUC defined as (AUC0-inf - AUC0-t)/AUC0-inf	From 0 hours after each drug intake (extrapolated to infinity).
Pharmacokinetics - t1/2	Elimination half-life (t1/2)	From 0 to 24 hours after each drug intake.
Pharmacokinetics - kel	Elimination constant (kel)	From 0 to 24 hours after each drug intake.
Pharmacokinetics - MRT	Mean residence time (MRT)	From 0 to 24 hours after each drug intake.
Pharmacokinetics - Vd	Volume of distribution	From 0 to 24 hours after each drug intake.
Pharmacokinetics - CL	Clearance (CL)	From 0 to 24 hours after each drug intake.
Pharmacokinetics - number of terminal timepoints	Number of points in the terminal logarithmic phase used to estimate the terminal elimination rate constant	From 0 to 24 hours after each drug intake.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event type	Adverse events will be assessed by complaints, results of physical examination, results of heart rate and blood pressure assessment, results of respiratory rate assessment, body temperature, laboratory monitoring (clinical blood count, biochemical blood count, urinalysis), electrocardiography; adverse events will be classified in accordance to MedDRA.	From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
Adverse event number	Number of adverse events registered during the study	From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
Adverse event severety	Severity of adverse events registered during the study	From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
Drop-outs associated with adverse events	The number of cases of early termination of participation in the study due to the development of adverse events and/or serious adverse events associated with the study drug	From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
Volunteer complaints	Description of complaints, recieved from volunteer	From screeninig (days -14 to -1) to the end of study (day 15 ± 1)
Physical examination results - cardiovascular system	An assessment of the condition of the cardiovascular system on physical examination (normal condition or list of abnormal conditions, if any)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Physical examination results - respiratory system	An assessment of the condition of the respiratory system on physical examination (normal condition or list of abnormal conditions, if any)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Physical examination results - digestive tract	An assessment of the condition of the digestive tract on physical examination (normal condition or list of abnormal conditions, if any)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Physical examination results - endocrine system	An assessment of the condition of the endocrine system on physical examination (normal condition or list of abnormal conditions, if any)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Physical examination results - musculoskeletal system	An assessment of the condition of the musculoskeletal system on physical examination (normal condition or list of abnormal conditions, if any)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Safety and Tolerability: physical examination results - nervous system	An assessment of the condition of the nervous system on physical examination (normal condition or list of abnormal conditions, if any)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Physical examination results - sensory systems	An assessment of the condition of the sensory systems on physical examination (normal condition or list of abnormal conditions, if any)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Physical examination results - skin/visible mucous membranes	An assessment of the condition of the skin/visible mucous membranes on physical examination (normal condition or list of abnormal conditions, if any)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Vital signs - systolic blood pressure	Systolic blood pressure (SBP, mmHg)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Vital signs - diastolic blood pressure	Diastolic blood pressure (DBP, mmHg)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Vital signs - heart rate	Heart rate (HR, bpm)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
Vital signs - body temperature (Celsius temperature scale)	Body temperature (Celsius temperature scale)	Screeninig (days -14 to -1), day -1 to 2, day 7 to 9, day 15 ± 1
12-lead electrocardiogram (ECG) - heart rate	12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: heart rate (beats per minute)	Screeninig (days -14 to -1), day 1, 2, 8, 9, 15 ± 1
12-lead electrocardiogram (ECG) - PQ interval	12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: PQ interval (is the period, measured in milliseconds, that extends from the beginning of the P wave (the onset of atrial depolarization) until the beginning of the QRS complex)	Screeninig (days -14 to -1), day 1, 2, 8, 9, 15 ± 1
12-lead electrocardiogram (ECG) - QRS complex	12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: QRS complex (the QRS complex is the combination of three of the graphical deflections seen on a typical electrocardiogram)	Screeninig (days -14 to -1), day 1, 2, 8, 9, 15 ± 1
12-lead electrocardiogram (ECG) - corrected QT interval	12-lead ECG (I, II, III, aVR-enhanced unipolar abduction from the right arm , aVL-enhanced unipolar abduction from the left arm, aVF - enhanced unipolar abduction from the left leg, V1-V6) taken while lying down: corrected QT interval (distance from the beginning of the QRS complex to the end of the T wave)	Screeninig (days -14 to -1), day 1, 2, 8, 9, 15 ± 1
Clinical blood test - hemoglobin	Hemoglobin (g/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - hematocrit	Hematocrit (%)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - red blood cell count	Red blood cell count (cells/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - platelet count	Platelet count (cells/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - leukocyte count	Leukocyte count (cells/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - erythrocyte sedimentation rate	Erythrocyte sedimentation rate (mm/h)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - myelocytes	Leukocyte formula (myelocytes, %)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - band neutrophils	Leukocyte formula (band neutrophils, %)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - segmented neutrophils	Leukocyte formula (segmented neutrophils, %)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - eosinophils	Leukocyte formula (eosinophils, %)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - basophils	Leukocyte formula (basophils, %)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - monocytes	Leukocyte formula (monocytes, %)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Clinical blood test - lymphocytes	Leukocyte formula (lymphocytes, %)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - specific gravity	Specific gravity of the urine	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - color	Color of the urine	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - transparency	Transparency of the urine	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - pH	pH of the urine	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - protein	Protein concentration (g/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - glucose	Glucose concentration (mmol/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - red blood cells	Red blood cell content (number in sight)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - white blood cells	White blood cell content (number in sight)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - epithelial cells	Epithelial cell content (number in sight)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - casts	Presence of casts (Yes/No)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - mucus	Presence of mucus (Yes/No)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis - bacteria	Presence of bacteria (Yes/No)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Urinalysis (microscopy)	Microscopy of urine sediment is performed if it is present	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Blood chemistry - glucose	Glucose concentration (mmol/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Blood chemistry - cholesterol	Total cholesterol concentration (mmol/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Blood chemistry - protein	Total protein concentration (g/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Blood chemistry - bilirubin	Total bilirubin concentration (micromol/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Blood chemistry - creatinine	Creatinine concentration (micromol/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Blood chemistry - alkaline phosphatase	Alkaline phosphatase activity (U/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Blood chemistry - alanine transaminase	Alanine transaminase activity (U/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1
Blood chemistry - aspartate transaminase	Aspartate transaminase activity (U/L)	Screeninig (days -14 to -1), day 2, 9, 15 ± 1

Collaborators and Investigators

• Sponsor: Valenta Pharm JSC

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 17, 2025
• First Submitted That Met QC Criteria: February 27, 2025
• First Posted (Actual): March 5, 2025

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 4, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Pharyngeal Diseases; Pharyngitis; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Infective Agents, Local; Cetylpyridinium; Gramicidin
• Other Study ID Numbers: GRM-01-05-2024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No