Food-Effect, Single and Multiple Dose Pharmacokinetics, Safety and Tolerability Study of 4-MUST, 128 mg, Tablets in Healthy Volunteers

NCT07594977 | Recruiting Phase 1

• 1 other identifier: GIB-01-05-2025
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This open-label study will evaluate the effect of food on the bioavailability of a single dose of 4-MUST, tablets, 128 mg. Additionally, the study will assess the pharmacokinetics, safety, and tolerability of 4-MUST, tablets, 128 mg following both single and multiple oral dose administration.

Conditions

Chronic Cholecystitis; Biliary Dyskinesia

Outcome Measures

Primary Outcomes (32)

• Pharmacokinetics - Cmax

  Maximum plasma concentration (Cmax) of 4-MUST metabolites: trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

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

• Pharmacokinetics - tmax

  Time to reach Cmax (tmax) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  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 trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  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 trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  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 trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

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

• Pharmacokinetics - kel

  Elimination constant (kel) of of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

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

• Pharmacokinetics - MRT

  Mean residence time (MRT) of of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

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

• Pharmacokinetics - Vd

  Volume of distribution of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  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 trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide under 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 of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide under 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 of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide under fasted and fed conditions (with 90% confidence intervals)

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

• Pharmacokinetics (multiple dosing) - number of terminal timepoints

  number of points in the terminal logarithmic phase used to estimate the terminal elimination rate constant of of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - Cmax

  Maximum plasma concentration (Cmax) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - tmax

  Time to reach Cmax (tmax) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - AUC0-t

  Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - AUC0-inf

  Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - AUCextr

  Extrapolated AUC of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - t1/2

  Elimination half-life (t1/2) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - kel

  Elimination constant (kel) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - MRT

  Mean residence time (MRT) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - Vd

  Volume of distribution of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - CL

  Clearance (CL) of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 72 to 120 hours

• Pharmacokinetics (multiple dosing) - Cmax,ss

  Maximum plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 0 to 72 hours

• Pharmacokinetics (multiple dosing) - tmax,ss

  Time to reach maximum plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 0 to 72 hours

• Pharmacokinetics (multiple dosing) - tmin,ss

  Time to reach minimum plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 0 to 72 hours

• Pharmacokinetics (multiple dosing) - Cmin,ss

  Minimum plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 0 to 72 hours

• Pharmacokinetics (multiple dosing) - Cavg,ss

  Average plasma concentration at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 0 to 72 hours

• Pharmacokinetics (multiple dosing) - CL,ss

  Clearance at steady state of trimebutine, N-desmethyltrimebutine, 3,4,5-trimethoxybenzoic acid, 4-methylumbelliferone sulfate, 4-methylumbelliferone and 4-methylumbelliferone glucuronide

  From 0 to 72 hours

Secondary Outcomes (54)

• 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)

• Physical examination results - cardiovascular system

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

Study Arms (3)

AB sequence

EXPERIMENTAL

Cohort 1, Group 1 (sequence AB) will receive 3 tablets (384 mg) of the study drug under fasting conditions in Period I and under fed conditions in Period II.

Drug: 4-MUST

BA sequence

EXPERIMENTAL

Cohort 1, Group 2 (sequence AB)will receive 3 tablets (384 mg) of the study drug under fed conditions in Period I and under fasting conditions in Period II.

Drug: 4-MUST

Multiple dosing

EXPERIMENTAL

Cohort 2, Multiple dose: 3 tablets (384 mg) three times daily, 30 minutes before meals, for 3 consecutive days (with the last dose taken in the morning of Day 4).

Drug: 4-MUST

Interventions

4-MUST DRUG

128 mg tablets containing trimebutine 4-methylumbelliferyl sulfate (4-MUST)

Also known as: trimebutine 4-methylumbelliferyl sulfate

AB sequence; BA sequence; Multiple dosing

Eligibility Criteria

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

You may qualify if:

• Voluntary, personally signed ICF obtained prior to any study procedures;
• Males and females aged 18 to 45 years (inclusive) of Caucasian race;
• Confirmed healthy status based on the absence of clinically significant abnormalities in clinical, laboratory, and diagnostic assessments specified in the protocol;
• Blood pressure (BP): 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;
• Commitment to adhere to highly effective contraceptive methods during the study participation period and for 30 days thereafter; documentation of negative urine pregnancy test for women of childbearing potential.
• History of clinically significant allergic reactions;
• Hypersensitivity to hymecromone and trimebutine and/or excipients included in the study drug in anamnesis;
• Drug intolerance to hymecromone and trimebutine and/or excipients included in the study drug 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;
• History of GI surgery (except for appendectomy at least 1 year prior to screening);

You may not qualify if:

• Voluntary withdrawal of the subject from the study;
• Failure to comply with protocol requirements by the volunteer (e.g., missing scheduled study procedures, unauthorized use of prohibited medications, or violation of dietary or lifestyle restrictions);
• Occurrence of any event or condition during the study that, in the investigator's judgement, may compromise the volunteer's safety (e.g., hypersensitivity reactions);
• 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 test;
• Positive pregnancy test in women;
• Occurrence of any other circumstance that precludes conduct of the study in accordance with the protocol.

Sponsors & Collaborators

• Valenta Pharm JSC: lead

Study Sites (1)

I.M. Sechenov First Moscow State Medical University

Moscow, 119991, Russia

RECRUITING

MeSH Terms

Conditions

Biliary Dyskinesia

Condition Hierarchy (Ancestors)

Common Bile Duct Diseases; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Design

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

Study Record Dates

• First Submitted: May 12, 2026
• First Posted: May 19, 2026
• Study Start: January 26, 2026
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 19, 2026

Record last verified: 2026-03

Locations

RU (1)