The primary purpose of this study is to demonstrate the bioequivalence of two ibuprofen arginine granules 400 milligram (mg) formulations under fasting and fed conditions in Chinese healthy adult participants. The secondary purpose of this study is to assess the pharmacokinetic and safety profile of the test and reference preparations.
The bioequivalence study adopts a single-center, randomized, open-label, single-dose, two-treatment, two-sequence, two-period, two-cohort, two-way crossover design with at least 2-day washout period, under both fasting and fed conditions in Chinese healthy adult participants. It will be planned to enroll approximately 84 participants out of which the first 34 participants for the fasted cohort and the subsequent 50 participants for the fed cohort receiving ibuprofen arginine granules 400 mg. Participants will be randomly assigned to either one of the 2 treatment (Test or Reference product) sequences in a 1:1 ratio within fasted cohort and fed cohort.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
84
Experimental- Ibuprofen arginine granules 400 mg, one sachet administration containing 400 mg ibuprofen granules.
Marketed drug- Ibuprofen arginine granules 400 mg (Spedifen), one sachet administration containing 400 mg ibuprofen granules.
Clinical Pharmacological Research Center
Wenjiang, Chengdu, China
Area Under the Plasma Concentration Time Curve From Time Zero to Last Observed Concentration at Time t (AUC[0-t]) for Ibuprofen in Fasted Conditions
AUC(0-t) was defined as area under the plasma concentration-time curve from time zero to last observed concentration at time t calculated using the linear up log down trapezoidal rule. Blood samples were collected at indicated timepoints for the analysis of AUC(0-t). Pharmacokinetic (PK) parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose
Area Under the Plasma Concentration Time Curve From Time Zero to Time Infinity (AUC [0-inf]) for Ibuprofen in Fasted Conditions
AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity, computed as AUC(0-inf) = AUC(0-t) +Ct/λz where Ct was the plasma concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints for the analysis of AUC(0-inf). PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose
Observed Maximum Plasma Concentration (Cmax) for Ibuprofen in Fasted Conditions
Cmax was defined as maximum observed post-dose plasma concentration for ibuprofen. Blood samples were collected at indicated timepoints for the analysis of Cmax. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose
AUC(0-t) for Ibuprofen in Fed Conditions
AUC(0-t) was defined as area under the plasma concentration-time curve from time zero to last observed concentration at time t calculated using the linear up log down trapezoidal rule. Blood samples were collected at indicated timepoints for the analysis of AUC(0-t). PK parameters were determined by non-compartmental analysis.
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Time frame: Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose
AUC (0-inf) for Ibuprofen in Fed Conditions
AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity, computed as AUC(0-inf) = AUC(0-t) +Ct/λz where Ct was the plasma concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints for the analysis of AUC(0-inf). PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose
Cmax for Ibuprofen in Fed Conditions
Cmax was defined as maximum observed post-dose plasma concentration for ibuprofen. Blood samples were collected at indicated timepoints for the analysis of Cmax. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose
Time to Reach Maximum Plasma Concentration (Tmax) of Ibuprofen in Fasted Conditions
Blood samples were collected at indicated timepoints for the analysis of Tmax. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose
Elimination Half-life (t1/2) of Ibuprofen in Fasted Conditions
t1/2 was defined as elimination half-life calculated as t1/2 = ln (2)/λz where λz was terminal elimination rate constant. Blood samples were collected at indicated timepoints for the analysis of t1/2. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose
Terminal Elimination Rate Constant (λz) of Ibuprofen in Fasted Conditions
λz was defined as terminal elimination rate constant estimated by log-linear regression of the terminal part of the plasma concentration versus time curve. Blood samples were collected at indicated timepoints for the analysis of λz. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose
Percentage of Extrapolated Area of AUC(0-inf) (%AUCex) of Ibuprofen in Fasted Conditions
%AUCex was calculated as %AUCex = (1- AUC\[0-t\] /AUC\[0-inf\])\*100%. Blood samples were collected at indicated timepoints for the analysis of %AUCex. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose
Tmax of Ibuprofen in Fed Conditions
Blood samples were collected at indicated timepoints for the analysis of Tmax. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose
t1/2 of Ibuprofen in Fed Conditions
t1/2 was defined as elimination half-life calculated as t1/2 = ln (2)/λz where λz was terminal elimination rate constant. Blood samples were collected at indicated timepoints for the analysis of t1/2. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose
λz of Ibuprofen in Fed Conditions
λz was defined as terminal elimination rate constant estimated by log-linear regression of the terminal part of the plasma concentration versus time curve. Blood samples were collected at indicated timepoints for the analysis of λz. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose
%AUCex of Ibuprofen in Fed Conditions
%AUCex was calculated as %AUCex = (1- AUC\[0-t\] /AUC\[0-inf\])\*100%. Blood samples were collected at indicated timepoints for the analysis of %AUCex. PK parameters were determined by non-compartmental analysis.
Time frame: Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose