This study is a single-center, open-label, multiple-dose trial performed in a 2-period, 2- sequence-cross-over design in healthy volunteers. The primary purpose of this study is to assess non-superiority of the bioavailability of TK-254RX compared with that of a marketed oral flurbiprofen-containing tablet formulation in healthy volunteers in a 2-period, 2- sequence-cross-over design and evaluate adhesion of TK-254RX. Secondary purpose is to assess safety of TK-254RX and residual amount of the patch.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
The total of two TK-254RX per day for 5 days (one patch applied to left and right lower leg above ankle)
3 tablets per day for 4 days
SocraTec R&D GmbH Clinical Pharmacology Unit
Mainzerhofplatz 14, Erfurt, Germany
Area under the plasma concentration versus time curve over 24 hours of S-flurbiprofen for TK-254RX and tablet under steady-state conditions
Time frame: Day 5 to Day 6
Peak Plasma Concentration of S-flurbiprofen for TK-254RX and tablet under steady-state conditions
Time frame: Day 5 to Day 6
Characterization of patch adhesion
Measuring patch adhesion area by percentage of visually by site staff with remaining patch adhered
Time frame: Day 1 to Day 6
Area under the plasma concentration versus time curve over 24 hours of S-flurbiprofen for TK-254RX on Day 1
Time frame: Day 1 to Day 2
Peak Plasma Concentration of S-flurbiprofen for TK-254RX on Day 1
Time frame: Day 1 to Day 2
Time to reach Peak Plasma Concentration of TK-254RX after the first two patches application on Day 1
Time frame: Day 1
Time before first concentration value above the lower limit of quantitation of TK-254RX after the first two patches application on Day 1
Time frame: Day 1
Trough concentration of TK-254RX
minimum concentration at the end of each dosing
Time frame: 24 hours, 48 hours, 72 hours, 96 hours, 120 hours after first TK-254RX application
Trough concentration of tablet
minimum concentration at the end of each dosing
Time frame: 24 hours, 48 hours, 72 hours, 96 hours after first tablet application
Area under the plasma concentration versus time curve of R- flurbiprofen and metabolites from the last two TK-254RX application to the time point of 24 hours under steady condition
Time frame: Day 5
Peak Plasma Concentration of R-flurbiprofen and metabolites under steady condition
Time frame: Day 5
Minimum plasma concentration of TK-254RX under steady condition
Time frame: Day 5
Time to reach Peak Plasma Concentration of TK-254RX under steady condition
Time frame: Day 5
Percentage of peak trough fluction of TK-254RX under steady condition
Time frame: Day 5
Average concentration at time points on Day 5 under steady condition
Time frame: Day 5
Area under the plasma concentration versus time curve from the last two TK-254RX application to last measurement time point with a concentration value above lower limit of quantitation
Time frame: Day 5 to Day 8
Percentage of area under the plasma concentration versus time curve extrapolated to infinity to area under the plasma concentration versus time curve from 0 hour to infinity of the last TK-254RX application
Time frame: Day 5 to Day 8
Area under the plasma concentration versus time curve from 0 hour to infinity of the last TK-254RX application
Time frame: Day 5 to Day 8
Concentration at the last time point with concentration value above the lower limit of quantitation of the last TK-254RX application
Time frame: Day 5 to Day 8
Last time point with concentration value above the lower limit of quantitation of the last TK-254RX application
Time frame: Day 5 to Day 8
Apparent terminal elimination half-life of TK-254RX
Time frame: Day 5 to Day 8
Apparent terminal elimination rate constant determined by log-linear regression of TK-254RX
Time frame: Day 5 to Day 8
Area under the plasma concentration versus time curve of R-flurbiprofen and metabolites over 24 hours under steady condition
Time frame: Day 4 to Day 7
Peak plasma concentration of R-flurbiprofen and metabolites of tablet under steady condition
Time frame: Day 4 to Day 7
Minimum plasma concentration of tablet under steady condition
Time frame: Day 4 to Day 7
Time to reach Peak Plasma Concentration of tablet under steady condition
Time frame: Day 4 to Day 7
Percentage of peak trough fluction of tablet under steady condition
Time frame: Day 4 to Day 7
Average concentration at time points of tablet under steady condition
Time frame: Day 4 to Day 7
Area under the plasma concentration versus time curve from the first tablet administration on day 4 to last measurement time point with a concentration value above lower limit of quantitation
Time frame: Day 4 to Day 7
Area under the plasma concentration versus time curve from 0 hour to infinity of tablet of administration on 4th day
Time frame: Day 4 to Day 7
Percentage of area under the plasma concentration versus time curve extrapolated to infinity to area under the plasma concentration versus time curve from 0 hour to infinity of tablet of administration on 4th day
Time frame: Day 4 to Day 7
Concentration at the last time point with concentration value above the lower limit of quantitation of tablet of administration on 4th day
Time frame: Day 4 to Day 7
Last time point with concentration value above the lower limit of quantitation of tablet of administration on 4th day
Time frame: Day 4 to Day 7
Apparent terminal elimination half-life of tablet
Time frame: Day 4 to Day 7
Apparent terminal elimination rate constant determined by log-linear regression of tablet
Time frame: Day 4 to Day 7
Local tolerability
Assessing the local tolerability by using the 8-point dermal response and other effects score according to FDA recommendation
Time frame: within 5 min after removal of each patch as well as 12 h, 24 h, and 36 h after removal of the last 2 patches on study Day 6
Residual amount of S-flurbiprofen
residual amount of S-flurbiprofen in used patch applied on Day 5
Time frame: Day 5 to Day 6
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