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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
24
2 tablets (256 mg), fasted
2 tablets (256 mg), after meals
Federal Budgetary Institution of Science "North-Western Scientific Center for Hygiene and Public Health"
Saint Petersburg, Russia
RECRUITINGPharmacokinetics - Cmax
Maximum plasma concentration (Cmax) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From 0 to 48 hours (days 1-3 and 8-10)
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Pharmacokinetics - MRT
Mean residence time (MRT) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Time frame: 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
Time frame: 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
Time frame: From 0 to 48 hours (days 1-3 and 8-10)
Pharmacokinetics - f'
f' - relative bioavailability (AUC(0-t)(fed)/AUC(0- t)(fasting))
Time frame: From 0 to 48 hours (days 1-3 and 8-10)
Pharmacokinetics - f''
f'' is the relative absorption rate (Cmax(fed)/Cmax(fasting))
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: From 0 to 48 hours (days 1-3 and 8-10)
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.
Time frame: From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)
Adverse event frequency
Number and frequency of adverse events registered during the study
Time frame: From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)
Adverse event severety
Severity of adverse events registered during the study
Time frame: From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)
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
Time frame: From day -14 - day -1 (screening) to day 16 ± 1 (end of the study)