To evaluate the food effect of Ibuprofen CR Tablets 600 mg (IBUCR), and its bioavailability comparison versus 3 doses of the reference arms including Advil® Ibuprofen Tablets 200 mg (IBUAdv) and Motrin® IB Ibuprofen Tablets 200 mg (IBUMot) in normal healthy volunteers.
This randomized, open label, four-way crossover phase I study is to evaluate the food effect of Ibuprofen CR Tablets 600 mg (IBUCR), and its bioavailability comparison versus 3 doses of the reference arms including Advil® Ibuprofen Tablets 200 mg (IBUAdv) and Motrin® IB Ibuprofen Tablets 200 mg (IBUMot) in normal healthy volunteers. This study will enroll at least 26 evaluable subjects. The duration for test and reference treatments is 24 to 32 hours with a washout period of at least 5 days after the last dose administration of study drugs. The total study will take at least 28 days. Subjects who meet all eligible requirements for participating in the study will receive all following interventions according to one of the 4 random sequences by Williams design. 1. One tablet of IBUCR 600 mg under fasting condition 2. One tablet of IBUCR 600 mg under fed condition 3. IBUAdv with a 4-hour dosing interval for 3 tablets (3×200 mg, q4h) under fasting condition 4. IBUMot with a 4-hour doing interval for 3 tablets (3×200 mg, q4h) under fasting condition The blood sampling schedule are described as follows: -For subjects receiving IBUCR (fed and fasted): Before dose administration (blank) and at 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 12h, 18h, 24h, 28h, 32h post-dose (A total of 17 samples per subject) -For subjects receiving IBUAdv/IBUMot (fasted): Before dose administration (blank) and at 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 8h, 8.5h, 9h, 9.5h, 10h, 10.5h, 11h, 12h, 16h, 20h, 24h post-dose (A total of 25 samples per subject)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
31
Administration of the comparator drug: Three tablets (dosing at a 4-hour interval, q4h) of reference ibuprofen standard products, followed by 24 hours after the first dose administration.
Administration of the comparator drug: Three tablets (dosing at a 4-hour interval, q4h) of reference ibuprofen standard products, followed by 24 hours after the first dose administration.
Administration of the investigational product: Single oral dose of IBUCR, followed by 28 and 32 hours after the dose administration for fasted and fed studies, respectively
Tri-Service General Hospital
Taipei, Taiwan
Area under the curve from time zero to the time of the last quantifiable plasma concentration of the period (AUC0-last)
The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation) of AUC0-last within \[0.8, 1.25\] range will be used to determine the result of bioequivalence.
Time frame: 1 month
Area under the curve from time zero to infinity (AUC0-inf)
The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation) of AUC0-inf within \[0.8, 1.25\] range will be used to determine the result of bioequivalence.
Time frame: 1 month
Peak concentration at each treatment period (Cmax,tp)
The 90% CI for the geometric mean ratios (i.e., antilog-transformation for 90% CI of difference with log transformation) of Cmax,tp within \[0.8, 1.25\] range will be used to determine the result of bioequivalence.
Time frame: 1 month
Peak concentration of the first dosing (Cmax)
Individual ibuprofen plasma concentration-time profile for each treatment period will be established.
Time frame: 1 month
Time to reach peak concentration of the first dosing (Tmax)
Individual ibuprofen plasma concentration-time profile for each treatment period will be established.
Time frame: 1 month
Terminal half-life (T1/2)
Individual ibuprofen plasma concentration-time profile for each treatment period will be established.
Time frame: 1 month
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Mean residence time (MRT)
Individual ibuprofen plasma concentration-time profile for each treatment period will be established.
Time frame: 1 month
The maximum ibuprofen plasma concentration within 1 hour after the first dose administration (Cmax0-1h)
The Cmax0-1h will be observed. The mean Cmax0-1h of test and reference treatments under fasting condition will be calculated. Percentage of the test drug-treated subjects with higher or equal Cmax0-1h compared to that of receiving the reference treatments under fasting condition will be calculated.
Time frame: 0.5h and 1h post-dose
The minimum ibuprofen plasma concentration within a time window of 1-12 hours after the first dose administration (Cmin1-12h)
The Cmin1-12h will be observed. The mean Cmin1-12h of test and reference treatments under fasting condition will be calculated.
Time frame: 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h and 12h post-dose
The mean time to drop to the Cmin1-12h of reference treatments
For the plasma ibuprofen concentration of test treatments under fasting condition, the mean time to drop to the Cmin1-12h of reference treatments will be calculated.
Time frame: 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h, 12h, 18h, 24h, 28h, 32h post-dose
Plasma ibuprofen concentrations at 8-hour (C8h) after the first dose administration
The C8h after the first dose administration will be observed (prior to the 8-hour dose administration for the reference treatments). The mean C8h of test and reference treatments under fasting condition will be calculated.
Time frame: 8-hour after the first dose administration
Plasma ibuprofen concentrations at 12-hour (C12h) after the first dose administration
The C12h after the first dose administration will be observed. The mean C12h of test and reference treatments under fasting condition will be calculated.
Time frame: 12-hour after the first dose administration
Percentage of the test drug-treated subjects with higher or equal C8h compared to that of receiving the reference treatments (before dose 3) under fasting condition
Time frame: 1 month
Percentage of the test drug-treated subjects with higher or equal C12h compared to that of receiving the reference treatments under fasting condition
Time frame: 1 month