Type 2 Diabetes Mellitus
Conditions
Keywords
Phase 1, healthy volunteers, cross-over study, Bioavailability, Bioequivalence, Cmax, tmax, AUC, AUC(0-t), λz, tlast
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
Interventions
DRUGDapagliflozin + Glucophage tablet fasted
Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fasted state
DRUGDapagliflozin/metformin IR FDC tablet fasted
single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fasted state
DRUGDapagliflozin + Glucophage tablet fed
Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fed state
DRUGDapagliflozin/metformin IR FDC tablet fed
single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fed state
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve over the time (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 | No statistical analysis will be performed |
| AUC 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 | No statistical analysis will be performed |
| Maximum 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 | No statistical analysis will be performed |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| Safety profile description in term of Electrocardiogram ECG | at screening and up to 10 days after final dose | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| Safety profile description in term of Adverse Events | from first dose in treatment period 1 up to 10 days after final dose | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
| 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 | No statistical analysis will be performed |
Countries
United Kingdom
Outcome results
None listed