Clinical trial NCT06342804: Food Effect on the Bioavailability of 4-MUST, Tablets, 128 mg
Official title: An Open-label Crossover Study With 2 Treatments (Fasting and Fed Conditions), 2 Periods, 2 Sequences to Evaluate the Effect of Food Intake on the Bioavailability of 4-MUST, Tablets, 128 mg at a Single Dose of 256 mg in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Cholecystitis
Lead sponsor: Valenta Pharm JSC
Sponsor class: INDUSTRY
First posted: 2024-04-02
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: Primary objective of the study: evaluation of the effect of food intake on the bioavailability of 4-MUST, tablets, 128 mg (Valenta Pharm JSC) after a single oral administration on an empty stomach and after a meal, at a dose of 256 mg (two tablets).

Additional aim of the study: evaluation of pharmacokinetic parameters, safety and tolerability of 4-MUST, tablets, 128 mg (Valenta Pharm JSC) in healthy volunteers after a single oral administration on an empty stomach and after a meal, at a dose of 256 mg (two tablets).


Eligibility criteria: Inclusion Criteria:

1. Voluntary and handwritten informed consent form signed by a healthy volunteer to participate in the study prior to any of the study procedures;
2. Males and females between the ages of 18 and 45 years (inclusive) of Caucasian race;
3. Verified diagnosis of "healthy" (absence of abnormalities according to the data of clinical, laboratory, instrumental methods of examination stipulated by the protocol);
4. Blood pressure (BP) level: systolic blood pressure (SBP) from 99 to 129 mmHg (inclusive), diastolic blood pressure (DBP) from 70 to 89 mmHg (inclusive);
5. Heart rate (HR) from 60 to 89 beats/min (inclusive);
6. Respiratory rate (RR) from 12 to 20 per 1 minute (inclusive);
7. Body temperature from 36.0°C to 36.9°C (inclusive);
8. 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;
9. Agreement to use adequate contraceptive methods throughout the study and for 30 days after completion of the study, for women of preserved reproductive potential, a negative urine pregnancy test result.

Noninclusion Criteria:

1. Aggravated allergic history;
2. Hypersensitivity to gimecromone and trimebutine and/or excipients included in the investigational medicinal product in anamnesis;
3. Drug intolerance to hymecromone and trimebutine and/or excipients included in the investigational medicinal product in the anamnesis;
4. Hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption in the anamnesis;
5. 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;
6. A history of GI surgery (except for appendectomy at least 1 year prior to screening);
7. Diseases/conditions that, in the opinion of the investigator, may affect the absorption, distribution, metabolism, or excretion of the investigational drug;
8. Acute infectious diseases less than 4 weeks prior to screening;
9. 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;
10. 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);
11. Blood or plasma donation less than 3 months prior to screening;
12. Use of hormonal contraceptives (in women) less than 2 months prior to screening;
13. Use of depot injections of any medicine less than 3 months prior to screening;
14. Pregnancy or lactation period; positive urine pregnancy test for women of preserved reproductive potential;
15. Women of preserved reproductive potential with a history of unprotected sexual intercourse within 30 days prior to study medication with an unsterilized partner;
16. Participation in another clinical trial less than 3 months prior to screening or concurrent with the present study;
17. Intake of more than 10 units of alcohol (1 unit of alcohol is equivalent to 500 mL of beer, 200 mL of wine, or 50 mL of spirits) per week in the last month prior to inclusion in the study or history of alcoholism, drug abuse, or medicine abuse;
18. 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;
19. Consumption of alcohol, caffeine, and xanthine-containing products in the 7 days prior to taking the study drug;
20. 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;
21. Dehydration due to diarrhea, vomiting, or other cause within the last 24 hours prior to taking the study drug;
22. 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;
23. Positive result of rapid test for coronavirus disease pathogen 2019 (Coronavirus disease 2019, COVID-19) at screening;
24. Clinically significant electrocardiogram (ECG) abnormalities with a history and/or at screening;
25. Positive urinalysis for narcotics and potent drugs at screening;
26. Positive breath alcohol vapor test at screening;
27. Scheduling a hospital stay during the study period, for any reason other than hospitalization required by this protocol;
28. Failure or inability to comply with protocol requirements, follow protocol procedures, diet and activity regimen.
29. Vulnerable group of volunteers: medical, pharmacy and dental students, clinical and laboratory assistants, pharmaceutical company employees, military personnel and prisoners, care home residents, low-income and unemployed, minorities, homeless, vagrants, refugees, persons in foster care, persons unable to consent, and law enforcement officers;
30. Other conditions that, in the opinion of the Investigator, would preclude the inclusion of the volunteer in the study or could result in early withdrawal of the volunteer from the study, including fasting or a special diet (e.g., vegetarian, vegan, limited table salt) or a special lifestyle (night work, extreme physical exertion).

Exclusion criteria:

1. The volunteer refuses to participate in the study;
2. Failure of the volunteer to comply with the rules of participation in the study (skipping study procedures, independent use of drugs prohibited in the study, violation of dietary and lifestyle restrictions, etc.);
3. Causes/occurrence of situations during the study that jeopardize the safety of the volunteer (e.g. hypersensitivity reactions, etc.);
4. Volunteers selected for participation in the study in violation of the inclusion/non-inclusion criteria;
5. Development of severe adverse event and/or a serious adverse event in a volunteer during the course of the study;
6. Volunteer is receiving or requires treatment that may affect the pharmacokinetic parameters of the study drug;
7. Missing collection of 2 or more consecutive blood samples or 3 x or more blood samples during the same Study Period;
8. Occurrence of vomiting/diarrhea within 6 h after administration of study drug;
9. Positive urine test for narcotics and potent drugs;
10. Positive breath alcohol vapor test;
11. A positive pregnancy test in women;
12. Positive test for COVID-19;
13. Occurrence of other reasons during the study that prevent the conduct of the study according to the protocol.

Primary outcomes:
measure: Pharmacokinetics - Cmax
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - tmax
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - AUC0-t
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - AUC0-inf
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - AUC ratio
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - t1/2
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - kel
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - MRT
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - Vd
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - Cmax/AUC0-t
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - f'
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Pharmacokinetics - f''
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Bioavailability - ratio of Cmax
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Bioavailability - ratio of AUC0-t
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
measure: Bioavailability - ratio of AUC0-inf
timeFrame: From 0 to 48 hours (days 1-3 and 8-10)
Secondary outcomes:
measure: Adverse event type
timeFrame: From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)
measure: Adverse event frequency
timeFrame: From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)
measure: Adverse event severety
timeFrame: From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)
measure: Drop-outs associated with adverse events
timeFrame: From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: Federal Budgetary Institution of Science "North-Western Scientific Center for Hygiene and Public Health"
Study officials:
References: