A Study to Assess the Bioequivalence of the fixed dose combination (FDC) of Dapagliflozin and Sitagliptin, and Dapagliflozin 10 mg and Sitagliptin 100 mg administered as individual tablets in Healthy Subject
This study will be a randomized, open-label, 2-period, 2-treatment, single-dose, crossover study in healthy subjects (males and females), performed at a single study center. The study will assess the bioequivalence between a dapagliflozin/sitagliptin FDC tablet (test formulation) and a free combination of dapagliflozin 10 mg + sitagliptin 100 mg co-administered as individual tablets (reference formulation) in fasted conditions to healthy subjects. The study will also assess the Pharmacokinetics (PK) and safety and tolerability of dapagliflozin 10 mg and sitagliptin 100 mg when co-administered as individual tablets and as an FDC tablet. The study will comprise: * A Screening Period of maximum 28 days. * Two Treatment Periods (Treatment A or B) * A final Safety Follow-up Visit 7 to 14 days after the last dosing with the Investigational medicinal product (IMP) (Treatment A or B). There will be a minimum washout period of 7 days and a maximum of 14 days between each treatment period. All subjects will receive a single dose of the following treatments after an overnight fast of 10 hours: * Treatment A: 1 × dapagliflozin/sitagliptin FDC tablet (test formulation). * Treatment B: 1 × dapagliflozin 10 mg tablet + 1 × sitagliptin 100 mg tablet co-administered as individual tablets (reference formulation). Subjects will be randomized to one of 2 treatment sequences: Treatment A followed by Treatment B or Treatment B followed by Treatment A.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Subjects will receive single dose of Dapagliflozin/sitagliptin FDC orally.
Subjects will receive 100 mg single dose of Sitagliptin orally.
Subjects will receive 10 mg single dose of Dapagliflozin orally.
Research Site
Berlin, Germany
Area under plasma concentration-time curve from zero to infinity (AUCinf)
To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)
To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Maximum observed plasma (peak) drug concentration (Cmax)
To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Time to reach peak or maximum observed concentration or response following drug administration (tmax)
To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz)
To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRTinf)
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To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz)
To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Volume of distribution (apparent) following extravascular administration (based on terminal phase) (Vz/F)
To demonstrate the fasted-state bioequivalence between a dapagliflozin/sitagliptin FDC tablet relative to dapagliflozin 10 mg + sitagliptin 100 mg when co administered as individual tablets in healthy subjects.
Time frame: Day 1, Day 2, Day 3 and Day 4
Area under plasma concentration-time curve from zero to infinity (AUCinf)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Area under the plasma concentration-curve from zero to the last quantifiable concentration (AUClast)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Maximum observed plasma (peak) drug concentration (Cmax)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Time to reach peak or maximum observed concentration or response following drug administration (tmax)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2λz)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRTinf)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Terminal rate constant, estimated by log-linear least squares regression of the terminal part of the concentration-time curve (λz)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Apparent total body clearance of drug from plasma after extravascular administration (CL/F)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Volume of distribution (apparent) following extravascular administration (based on terminal phase) (Vz/F)
To characterize the PK profiles of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects in a fasted state.
Time frame: Day 1, Day 2, Day 3 and Day 4
Number of subjects with adverse events (AEs)
To assess the safety and tolerability of single doses of a dapagliflozin/sitagliptin FDC tablet and dapagliflozin 10 mg + sitagliptin 100 mg when co-administered as individual tablets in healthy subjects.
Time frame: From screening (Day -28) to Safety Follow-up (7 to 14 days after the last dosing with the IMP) [up to 66 days]