A Bioequivalence Study of the Fixed Dose Combination Dapagliflozin/Metformin Tablet (5 mg/850 mg) Relative to a 5 mg Dapagliflozin Tablet and an 850 mg Metformin (Glucophage® Marketed in Canada by Sanofi-Aventis) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed States
Overview
- Phase
- Phase 1
- Intervention
- Dapagliflozin + Glucophage tablet fed
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- AstraZeneca
- Enrollment
- 71
- Locations
- 1
- Primary Endpoint
- Area under the curve over the time (AUC)
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This is an open-label, randomised study to compare the similarity of a combination Dapagliflozin/Metformin tablet with the two drugs administered separately under fasting and fed conditions in healthy volunteers.
Detailed Description
A Bioequivalence Study of the Fixed Dose Combination Dapagliflozin/Metformin Tablet (5.0 mg/850 mg) Relative to a 5.0 mg Dapagliflozin Tablet and an 850 mg Metformin (Glucophage® Marketed in Canada by Sanofi-Aventis) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed States
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy volunteers aged 18 to 55 years inclusive with suitable veins for cannulation or repeated vein puncture
- •Male subjects should be willing to use barrier contraception ie, condoms and spermicide, from the day of dosing until at least 3 months after dosing with the investigational product
- •Non-pregnant, non-lactating female subjects who if pre-menopausal are using adequate birth control eg, oral, injectable, transdermal or implanted hormonal contraceptives, vaginal contraceptive ring, intrauterine device (IUD)/intrauterine systems
- •Have a body mass index (BMI) between 18.5 and 30.0 kg/m2 inclusive (ie, within 15% of normal range) and weigh at least 50 kg and no more than 100 kg.
Exclusion Criteria
- •History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
- •Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with individual safety evaluation Current smokers who smoke more than 5 cigarettes per day (or equivalent use of tobacco products) or cannot give up smoking during the study
- •Excessive intake of caffeine containing drinks eg, coffee, tea, caffeine containing energy drinks and cola (more than 5 cups of coffee or equivalent per day)
- •Plasma donation within one month of screening or any blood donation/blood loss \>500 mL during the 3 months prior to screening
Arms & Interventions
3
5 mg dapagliflozin and 850 mg Glucophage in fed state
Intervention: Dapagliflozin + Glucophage tablet fed
1
5 mg dapagliflozin and 850 mg Glucophage in fasted state
Intervention: Dapagliflozin + Glucophage tablet fasted
2
dapagliflozin/metformin (5 mg/850 mg) immediate release (IR) FDC in fasted
Intervention: Dapagliflozin/metformin IR FDC tablet fasted
4
dapagliflozin/metformin (5 mg/850 mg) IR FDC in fed state
Intervention: Dapagliflozin/metformin IR FDC tablet fed
Outcomes
Primary Outcomes
Area under the curve over the time (AUC)
Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose
No statistical analysis will be performed
AUC from time zero to the time of last quantifiable analyte concentration (AUC(0-t))
Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose
No statistical analysis will be performed
Maximum concentration (Cmax)
Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose
No statistical analysis will be performed
Secondary Outcomes
- Terminal rate constant (λz)(pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose)
- Time to reach maximum analyte concentration (tmax)(pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose)
- Time of last quantifiable analyte concentration (tlast)(pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose)
- Terminal half-life (t1/2)(pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose)
- Observed maximum analyte concentration (Cmax)(pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose)
- Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)(pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose)
- Elimination terminal half-life (t1/2)(pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose)
- Safety profile description in term of Blood Pressure(at screening, once daily during the residential period (5 days each) and up to 10 days after final dose)
- Safety profile description in term of Physical Examination(at screening, Day -1 and Day 4 at Visits 2 to 5 and up to 10 days after final dose)
- Safety profile description in term of Electrocardiogram ECG(at screening and up to 10 days after final dose)
- Safety profile description in term of Heart Rate(at screening, once daily during the residential period (5 days each) and up to 10 days after final dose)
- Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUC(0 t))(pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose)
- Safety profile description in term of Adverse Events(from first dose in treatment period 1 up to 10 days after final dose)
- Safety profile description in term of Safety Labs(at screening, on Day -1 and Day 4 (72 hours post-dose) at Visits 2 to 5 and up to 10 days after final dose)