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
Overview
- Phase
- Phase 1
- Intervention
- 4-MUST, 2 tablets, fasted
- Conditions
- Cholecystitis
- Sponsor
- Valenta Pharm JSC
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Pharmacokinetics - Vd
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •Noninclusion Criteria:
Exclusion Criteria
- Not provided
Arms & Interventions
AB sequence
Group 1 (sequence AB) will take the drug on an empty stomach in Period I and after a meal in Period II
Intervention: 4-MUST, 2 tablets, fasted
AB sequence
Group 1 (sequence AB) will take the drug on an empty stomach in Period I and after a meal in Period II
Intervention: 4-MUST, 2 tablets, after meals
BA sequence
Group 2 (BA sequence) will take the drug after a meal in Period I and on an empty stomach in Period II
Intervention: 4-MUST, 2 tablets, fasted
BA sequence
Group 2 (BA sequence) will take the drug after a meal in Period I and on an empty stomach in Period II
Intervention: 4-MUST, 2 tablets, after meals
Outcomes
Primary Outcomes
Pharmacokinetics - Vd
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Volume of distribution of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Pharmacokinetics - AUC0-t
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Area under the plasma concentration-time curve from time 0 to t (AUC0-t) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Pharmacokinetics - t1/2
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Elimination half-life (t1/2) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Pharmacokinetics - f'
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
f' - relative bioavailability (AUC(0-t)(fed)/AUC(0- t)(fasting))
Pharmacokinetics - AUC0-inf
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Pharmacokinetics - MRT
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Mean residence time (MRT) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Pharmacokinetics - Cmax/AUC0-t
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
The ratio of the maximum concentration to the area under the concentration-time curve during the observation period
Bioavailability - ratio of Cmax
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Ratio of geometric mean Cmax for N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone in fasted and fed conditions (with 90% confidence intervals)
Bioavailability - ratio of AUC0-inf
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Ratio of geometric mean AUC0-inf for N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone in fasted and fed conditions (with 90% confidence intervals)
Pharmacokinetics - tmax
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Time to reach Cmax (tmax) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Pharmacokinetics - AUC ratio
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
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
Pharmacokinetics - Cmax
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Maximum plasma concentration (Cmax) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Pharmacokinetics - kel
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Elimination constant (kel) of N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone
Pharmacokinetics - f''
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
f'' is the relative absorption rate (Cmax(fed)/Cmax(fasting))
Bioavailability - ratio of AUC0-t
Time Frame: From 0 to 48 hours (days 1-3 and 8-10)
Ratio of geometric mean AUC0-t for N-desmethyltrimebutin, 4-methylumbelliferone sulfate and 4-methylumbelliferone in fasted and fed conditions (with 90% confidence intervals)
Secondary Outcomes
- Adverse event type(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))
- Adverse event frequency(From day -14 - day -1 (screening) to day 16 ± 1 (end of the study))