Food Effect on the Bioavailability of 4-MUST, Tablets, 128 mg

NCT06342804 | Recruiting Phase 1

• 1 other identifier: GIB-01-02-2023
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

Cholecystitis

Outcome Measures

Primary Outcomes (15)

• Pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - tmax

  Time to reach Cmax (tmax) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - AUC0-t

  Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - AUC0-inf

  Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - AUC ratio

  The ratio of the area under the concentration-time curve over the observation time to the calculated area under the concentration-time curve from zero to infinity

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - t1/2

  Elimination half-life (t1/2) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - kel

  Elimination constant (kel) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - MRT

  Mean residence time (MRT) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - Vd

  Volume of distribution of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - Cmax/AUC0-t

  The ratio of the maximum concentration to the area under the concentration-time curve during the observation period

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - f'

  f' - relative bioavailability (AUC(0-t)(fed)/AUC(0- t)(fasting))

  From 0 to 48 hours (days 1-3 and 8-10)

• Pharmacokinetics - f''

  f'' is the relative absorption rate (Cmax(fed)/Cmax(fasting))

  From 0 to 48 hours (days 1-3 and 8-10)

• Bioavailability - ratio of Cmax

  Ratio of geometric mean Cmax for N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone in fasted and fed conditions (with 90% confidence intervals)

  From 0 to 48 hours (days 1-3 and 8-10)

• Bioavailability - ratio of AUC0-t

  Ratio of geometric mean AUC0-t for N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone in fasted and fed conditions (with 90% confidence intervals)

  From 0 to 48 hours (days 1-3 and 8-10)

• Bioavailability - ratio of AUC0-inf

  Ratio of geometric mean AUC0-inf for N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone in fasted and fed conditions (with 90% confidence intervals)

  From 0 to 48 hours (days 1-3 and 8-10)

Secondary Outcomes (4)

• Adverse event type

  From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)

• Adverse event frequency

  From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)

• Adverse event severety

  From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)

• Drop-outs associated with adverse events

  From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)

Study Arms (2)

AB sequence

EXPERIMENTAL

Group 1 (sequence AB) will take the drug on an empty stomach in Period I and after a meal in Period II

Drug: 4-MUST, 2 tablets, fasted; Drug: 4-MUST, 2 tablets, after meals

BA sequence

EXPERIMENTAL

Group 2 (BA sequence) will take the drug after a meal in Period I and on an empty stomach in Period II

Drug: 4-MUST, 2 tablets, fasted; Drug: 4-MUST, 2 tablets, after meals

Interventions

4-MUST, 2 tablets, fasted DRUG

2 tablets (256 mg), fasted

Also known as: 4-methylumbelliferyl trimebutine sulfate

AB sequence; BA sequence

4-MUST, 2 tablets, after meals DRUG

2 tablets (256 mg), after meals

Also known as: 4-methylumbelliferyl trimebutine sulfate

AB sequence; BA sequence

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntary and handwritten informed consent form signed by a healthy volunteer to participate in the study prior to any of the study procedures;
• Males and females between the ages of 18 and 45 years (inclusive) of Caucasian race;
• Verified diagnosis of "healthy" (absence of abnormalities according to the data of clinical, laboratory, instrumental methods of examination stipulated by the protocol);
• Blood pressure (BP) level: 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;
• 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.
• Aggravated allergic history;
• Hypersensitivity to gimecromone and trimebutine and/or excipients included in the investigational medicinal product in anamnesis;
• Drug intolerance to hymecromone and trimebutine and/or excipients included in the investigational medicinal product 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;
• A history of GI surgery (except for appendectomy at least 1 year prior to screening);

You may not qualify if:

• The volunteer refuses to participate in the study;
• 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.);
• Causes/occurrence of situations during the study that jeopardize the safety of the volunteer (e.g. hypersensitivity reactions, etc.);
• 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 vapor test;
• A positive pregnancy test in women;
• Positive test for COVID-19;
• Occurrence of other reasons during the study that prevent the conduct of the study according to the protocol.

Sponsors & Collaborators

• Valenta Pharm JSC: lead

Study Sites (1)

Federal Budgetary Institution of Science "North-Western Scientific Center for Hygiene and Public Health"

Saint Petersburg, 191036, Russia

RECRUITING

MeSH Terms

Conditions

Cholecystitis

Interventions

Postprandial Period

Condition Hierarchy (Ancestors)

Gallbladder Diseases; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Digestive System Physiological Phenomena; Digestive System and Oral Physiological Phenomena

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: April 2, 2024
• Study Start: March 19, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 2, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)