Safety, Tolerability and Pharmacokinetics of 4-MUST, Tablets, 128 mg (Valenta Pharm JSC) During Single and Multiple Oral Administration in Healthy Volunteers

NCT06315387 | Recruiting Phase 1

• 1 other identifier: GIB-01-01-2023
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Study of safety, tolerability and pharmacokinetic parameters of different doses of 4-MUST, tablets, 128 mg (Valenta Pharm JSC) in healthy volunteers

Conditions

Cholecystitis

Outcome Measures

Primary Outcomes (11)

• Pharmacokinetics - Cmax

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

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

• Pharmacokinetics - tmax

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

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

• 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, (single dose); from 0 to 120 hours (multiple dose)

• 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, (single dose); from 0 to 120 hours (multiple dose)

• Pharmacokinetics - AUCextr

  Extrapolated AUC of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone, defined as (AUC0-inf - AUC0-t)/AUC0-inf

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

• Pharmacokinetics - t1/2

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

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

• Pharmacokinetics - kel

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

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

• Pharmacokinetics - MRT

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

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

• Pharmacokinetics - Vd

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

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

• Pharmacokinetics - CL

  Clearance (CL) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

• Pharmacokinetics - number of terminal timepoints

  number of points in the terminal logarithmic phase used to estimate the terminal elimination rate constant of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone

  From 0 to 48 hours, (single dose); from 0 to 120 hours (multiple dose)

Secondary Outcomes (4)

• Adverse event type

  From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period)

• Adverse event frequency

  From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period)

• Adverse event severety

  From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period)

• Drop-outs associated with adverse events

  From Day -14 to Day -1 (screening), from Day 1 to Day 21 (single dosing and subsequent wash-out period), from Day 1 to Day 11 (multiple dosing and subsequent observation period)

Study Arms (3)

4-MUST, 128 mg

EXPERIMENTAL

Single dose: 1 tablet (128 mg). Multiple dose: 1 tablet (128 mg) 3 times a day for 3 days (first dose on an empty stomach, second and third two hours after meals), once in the morning on an empty stomach on day 4.

Drug: 4-MUST, 1 tablet

4-MUST, 256 mg

EXPERIMENTAL

Single dose: 2 tablets (256 mg). Multiple dose: 2 tablets (256 mg) 3 times a day for 3 days (the first intake of the drug on an empty stomach, the second and third - two hours after a meal), once in the morning on an empty stomach on the 4th day.

Drug: 4-MUST, 2 tablets

4-MUST, 384 mg

EXPERIMENTAL

Single dose: 3 tablets (384 mg). Multiple dose: 3 tablets (384 mg) 3 times a day for 3 days (the first intake of the drug on an empty stomach, the second and third - two hours after a meal), once in the morning on an empty stomach on the 4th day.

Drug: 4-MUST, 3 tablets

Interventions

4-MUST, 1 tablet DRUG

4-methylumbelliferyl trimebutine sulfate, 128 mg

4-MUST, 128 mg

4-MUST, 2 tablets DRUG

4-methylumbelliferyl trimebutine sulfate, 256 mg

4-MUST, 256 mg

4-MUST, 3 tablets DRUG

4-methylumbelliferyl trimebutine sulfate, 384 mg

4-MUST, 384 mg

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 between 36.0°C and 36.9°C (inclusive);
• Body mass index (BMI) of 18.5 kg/m2 ≤ BMI ≤ 30 kg/m2, with body mass ≥ 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 GIT surgery (except for appendectomy at least 1 year prior to screening);

You may not qualify if:

• Withdrawal of the volunteer from further participation 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 serious/severe adverse event in a volunteer during the course of the study;
• Volunteer is receiving or requires treatment that may affect the pharmacokinetics of the study drug;
• Missing collection of 2 or more consecutive blood samples or 3 or more blood samples during a single Study Period;
• Occurrence of vomiting/diarrhea within 6 h of administration of study drug;
• Positive urine test for narcotics and potent drugs;
• Positive breath alcohol vapor test;
• A positive pregnancy test in women;
• A 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)

Limited Liability Company "Medical Center Eco-Safety"

Saint Petersburg, 19119, Russia

RECRUITING

MeSH Terms

Conditions

Cholecystitis

Condition Hierarchy (Ancestors)

Gallbladder Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Design

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

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: March 18, 2024
• Study Start: December 4, 2023
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: March 18, 2024

Record last verified: 2024-02

Locations

RU (1)