An open-label, randomized, 3-way crossover study to evaluate the pharmacokinetics of investigational product "Ibuprofen Modified-Release Tablets 800 mg" in comparison to the reference standard "Ibuprofen Regular-Release Tablets 600 mg/800 mg" in normal healthy volunteers Primary objective: To evaluate the food effect of IBUMR and its bioavailability of single and multiple doses compared with reference drugs in normal healthy volunteers. Secondary objectives: 1. To determine and compare the single and multiple dose PK profiles of IBUMR and reference drugs. 2. To identify the effect duration for IBUMR after dose administration by detecting ibuprofen concentrations in plasma. 3. To evaluate the safety profile of single and multiple doses of IBUMR.
This study consists of 3 treatment periods as below. For Treatment A and Treatment B, single- and multiple-dose stages are included. Treatment A: One tablet of IBUMR will be administered to the subjects under fasted condition, followed by a minimum of 72-hour washout interval. After the washout period, subjects will receive 1 × IBUMR every 12 hours for a total of 8 doses. Treatment B: One tablet of IBURed-800mg will be administered to the subjects under fasted condition, followed by a minimum of 72-hour washout interval. After the washout period, subjects will receive 1 × IBURed-600mg every 8 hours for a total of 12 doses. Treatment C: Single dose of IBUMR will be given to the subjects under fed condition (a standard high-fat, high calorie breakfast should be consumed within 30 minutes prior to dosing). A minimum of 3-day washout interval will be introduced across the 3 treatment periods. Subjects will be required to be fasted for at least 10 hours prior to the administration of morning doses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Treatment A: One tablet of IBUMR will be administered to the subjects under fasted condition, followed by a minimum of 72-hour washout interval. After the washout period, subjects will receive 1 × IBUMR every 12 hours for a total of 7 doses. Treatment B: One tablet of IBURed will be administered to the subjects under fasted condition, followed by a minimum of 72-hour washout interval. After the washout period, subjects will receive 1 × IBURed every 8 hours for a total of 10 doses. Treatment C: Single dose of IBUMR will be given to the subjects under fed condition (a standard high-fat, high calorie breakfast should be consumed within 30 minutes prior to dosing).
Taipei Medical University Hospital
Taiwan, China
Comparison of single-dose and multiple-dose bioavailability between IBUMR and IBURed
Comparison of single-dose and multiple-dose bioavailability between IBUMR and IBURed in log-transformed values of area under the curve from time 0 to the last measurable concentration (AUCL)
Time frame: After collecting blood samples from the last participant, up to 30 days
Comparison of single-dose and multi-dose bioavailability of IBUMR and IBURed
Comparison of single-dose and multiple-dose bioavailability between IBUMR and IBURed in log-transformed values of the peak concentration (Cmax)
Time frame: After collecting blood samples from the last participant, up to 30 days
Comparison of single - and multi-dose bioavailability of IBUMR and IBURed
Comparison of single-dose and multiple-dose bioavailability between IBUMR and IBURed in log-transformed values of area under the curve from time 0 to infinity (AUCinf).
Time frame: After collecting blood samples from the last participant, up to 30 days
To assess the food effect of IBUMR in the PK parameters
To assess the food effect of IBUMR in the PK parameters including Cmax
Time frame: After collecting blood samples from the last participant, up to 30 days
To evaluate the food effect of IBUMR on PK parameters
To assess the food effect of IBUMR in the PK parameters including time to reach peak concentration (Tmax)
Time frame: After collecting blood samples from the last participant, up to 30 days
To evaluate the food effects of IBUMR on PK parameters
To assess the food effect of IBUMR in the PK parameters including AUCL
Time frame: After collecting blood samples from the last participant, up to 30 days
Evaluate the food effect of IBUMR in PK parameters
To assess the food effect of IBUMR in the PK parameters including AUCinf
Time frame: After collecting blood samples from the last participant, up to 30 days
Determine the food effect of IBUMR in PK parameters
To assess the food effect of IBUMR in the PK parameters including elimination half-life (t1/2)
Time frame: After collecting blood samples from the last participant, up to 30 days
Single-dose PK measures
\-- Time to reach peak concentration (Tmax)
Time frame: After collecting blood samples from the last participant, up to 30 days
Single dose PK method
\-- Area under the concentration-time curve within time span t1 to t2 (AUCt1→t2)
Time frame: After collecting blood samples from the last participant, up to 30 days
Single dose PK
\-- Area under the concentration-time curve extrapolated from the last detectable sampling time point to infinity as a percentage of total AUC (AUCextrap)
Time frame: After collecting blood samples from the last participant, up to 30 days
Single dose PK step
\-- Elimination half-life (t1/2)
Time frame: After collecting blood samples from the last participant, up to 30 days
Single dose PK design
\-- Apparent oral clearance (CL/F)
Time frame: After collecting blood samples from the last participant, up to 30 days
Single dose PK moves
\-- Apparent volume of distribution after oral administration (Vd/F)
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple-dose PK measures
\-- Peak concentration at steady state (Cmax,ss)
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple - dosed PK
\-- Plasma drug concentration at a specified time t steady state (Ct,ss)
Time frame: After collecting blood samples from the last participant, up to 30 days
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Multiple - dosed PK method
\-- Average concentration at steady state (Cavg)
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple - dosed PK steps
\-- Trough plasma concentration at steady state (Ctrough)
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple - dosed PK design
\-- Time to reach peak concentration at steady state (Tmax,ss)
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple - dosed PK plan
\-- Area under the concentration-time curve within time span t1 to t2 at steady state (AUCt1→t2,ss)
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple - dosed PK program
\-- AUC in 1 dosing interval (AUCτ) at steady state
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple - dosed PK process
\-- Terminal half-life at steady state (t1/2,ss)
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple - dosed PK arrangement
\-- Apparent oral clearance at steady state (CL/Fss)
Time frame: After collecting blood samples from the last participant, up to 30 days
Multiple - dosed PK planning
\-- Apparent volume of distribution after oral administration at steady state (Vd/Fss)
Time frame: After collecting blood samples from the last participant, up to 30 days
Assessment of effect duration for IBUMR
\-- For the plasma ibuprofen concentration of IBUMR at steady state, the time to drop to the Ctrough of IBURed-600mg will be calculated.
Time frame: After collecting blood samples from the last participant, up to 30 days
Evaluation of duration of IBUMR effect
\-- Percentage of the test drug-treated subjects with higher or equal plasma ibuprofen concentrations at 12-hour at steady state (C12,ss) compared to the Ctrough of IBURed-600mg will be calculated.
Time frame: After collecting blood samples from the last participant, up to 30 days
Incidence of treatment-emergent adverse events (safety and tolerability)
Incidence of AEs and SAEs
Time frame: After collecting blood samples from the last participant, up to 60 days
safety and tolerability
incidence of abnormal Physical examination
Time frame: After collecting blood samples from the last participant, up to 60 days
Incidence of treatment-emergent adverse events
abnormal Vital signs
Time frame: After collecting blood samples from the last participant, up to 60 days
Incidence of sudden adverse events (safety and tolerability)
abnormal laboratory tests results
Time frame: After collecting blood samples from the last participant, up to 60 days
Incidence of treatment-induced adverse events (safety and tolerability)
abnormal 12-lead ECG exams
Time frame: After collecting blood samples from the last participant, up to 60 days