The Purpose of the Study is to Compare Two Fixed Dose Combination Tablets of Dapagliflozin/Metformin XR in Healthy Subjects Under Fasting and Fed Conditions
- Conditions
- Healthy Subjects in Fasted and Fed State
- Interventions
- Drug: Dapagliflozin/metformin XR 5/500mgDrug: Dapagliflozin/metformin XR 10/1000mgDrug: Dapagliflozin/metformin XR 5/500 mg
- Registration Number
- NCT03216278
- Lead Sponsor
- AstraZeneca
- Brief Summary
This is a bioequivalence study of two doses of the dapagliflozin/metformin XR tablet manufactured at two different plants.
- Detailed Description
This is a two part, open-label, randomized, 4-period, 4-treatment (per study part) crossover study in healthy subjects (males and females of non-childbearing potential), performed at a single study center, conducted to establish the bioequivalence of 2 strengths of dapagliflozin/metformin XR tablets manufactured at two different plants.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 284
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment A Dapagliflozin/metformin XR 5/500mg Dapagliflozin/metformin XR 5/500 Mount Vernon Test Product Fed Treatment C Dapagliflozin/metformin XR 5/500mg Dapagliflozin/metformin XR 5/500 Mount Vernon Test Product Fasted Treatment G Dapagliflozin/metformin XR 10/1000mg Dapagliflozin/metformin XR 10/1000 Mount Vernon Test Product Fasted Treatment E Dapagliflozin/metformin XR 10/1000mg Dapagliflozin/metformin XR 10/1000 Mount Vernon Test Product Fed Treatment B Dapagliflozin/metformin XR 5/500 mg Dapagliflozin/metformin XR 5/500 Humacao Reference Product Fed Treatment D Dapagliflozin/metformin XR 5/500mg Dapagliflozin/metformin XR 5/500 Humacao Reference Product Fasted Treatment H Dapagliflozin/metformin XR 10/1000mg Dapagliflozin/metformin XR 10/1000 Humacao Reference Product Fasted Treatment F Dapagliflozin/metformin XR 10/1000mg Dapagliflozin/metformin XR 10/1000 Humacao Reference Product Fed
- Primary Outcome Measures
Name Time Method Part 1 - Area under the plasma concentration versus time curve (AUC) for each analyte and each state Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times To demonstrate the bioequivalence of dapagliflozin/metformin XR 5/500 mg manufactured at Mount Vernon plant and dapagliflozin/metformin XR 5/500 mg manufactured at Humacao plant in metformin and in dapagliflozin plasma concentrations for the fed state and, separately, the fasted state.
Part 2 - Area under the plasma concentration versus time curve (AUC) for each analyte and each state Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times To demonstrate the bioequivalence of dapagliflozin/metformin XR 10/1000 mg manufactured at Mount Vernon plant and dapagliflozin/metformin XR 10/1000 mg manufactured at Humacao plant in metformin and dapagliflozin plasma concentrations for the fed state and, separately, the fasted state.
Part 1 - Peak Plasma Concentration (Cmax) for each analyte and each state Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times To demonstrate the bioequivalence of dapagliflozin/metformin XR 5/500 mg manufactured at Mount Vernon plant and dapagliflozin/metformin XR 5/500 mg manufactured at Humacao plant in metformin and in dapagliflozin plasma concentrations for the fed state and, separately, the fasted state.
Part 2 - Peak Plasma Concentration (Cmax) for each analyte and each state Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times To demonstrate the bioequivalence of dapagliflozin/metformin XR 10/1000 mg manufactured at Mount Vernon plant and dapagliflozin/metformin XR 10/1000 mg manufactured at Humacao plant in metformin and in dapagliflozin plasma concentrations for the fed state and, separately, the fasted state.
- Secondary Outcome Measures
Name Time Method Time to reach maximum plasma concentration (tmax) Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times Measurements of tmax for dapagliflozin and metformin when administered in both fed and fasted states as single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants.
Area under plasma concentration - time curve from time zero to infinity (AUC) Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times Measurements of AUC from time zero to infinity for dapagliflozin and metformin when administered as single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants both fed and fasted states.
Blood pressure 10,5 weeks To evaluate the safety of single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants both fed and fasted states by assessing changes from baseline in mmHg of systolic and diastolic blood pressure.
Apparent total body clearance after extravascular administration (CL/F) Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times Measurements of apparent total body clearance after extravascular administration (CL/F) for dapagliflozin and metformin when administered in both fed and fasted states as single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants.
Laboratory assessments - hematology 10,5 weeks To evaluate the safety of single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants both fed and fasted states by assessing changes from baseline in hematology.
Electrocardiogram (ECG) 10,5 weeks To evaluate the safety of single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants both fed and fasted states by assessing changes from baseline in overall ECG evaluation.
Terminal elimination rate constant (λz) Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times Measurements of terminal elimination rate constant (λz) for dapagliflozin and metformin when administered in both fed and fasted states as single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants.
Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times Measurements of apparent volume of distribution during the terminal phase after extravascular administration (Vz/F) for dapagliflozin and metformin when administered in both fed and fasted states as single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants.
Adverse events 10,5 weeks To evaluate the safety of single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants both fed and fasted states by assessing the number of subjects with adverse events.
Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz) Based on pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48 and 72 hours post-dose sampling times Measurements of half-life associated with terminal slope (t½λz) for dapagliflozin and metformin when administered in both fed and fasted states as single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants.
Heart rate 10,5 weeks To evaluate the safety of single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants both fed and fasted states by assessing changes from baseline in heart rate measured as beats per minute.
Laboratory assessments - clinical chemistry 10,5 weeks To evaluate the safety of single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants both fed and fasted states by assessing changes from baseline in clinical chemistry.
Laboratory assessments - urinalysis 10,5 weeks To evaluate the safety of single doses of dapagliflozin/metformin 5/500 mg or 10/1000 mg formulation from both the Mount Vernon and Humacao plants both fed and fasted states by assessing changes from baseline in urinalysis.
Trial Locations
- Locations (1)
Research Site
🇧🇷Aparecida de Goiania, Brazil