To Compare the Similarity of a Combination Dapagliflozin/Metformin Tablet With the Two Drugs Administered Separately

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Dapagliflozin/metformin IR FDC tablet fed; Drug: Dapagliflozin + Glucophage tablet fasted; Drug: Dapagliflozin/metformin IR FDC tablet fasted; Drug: Dapagliflozin + Glucophage tablet fed

• Registration Number: NCT01535677
• Lead Sponsor: AstraZeneca

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

Study Timeline

• Study First Submitted: 2012-01-13
• Study First Submitted QC: 2012-02-15
• Study First Posted: 2012-02-20
• Study Start: 2013-04
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-08
• Last Update Posted: 2015-07-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 71

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
4	Dapagliflozin/metformin IR FDC tablet fed	dapagliflozin/metformin (5 mg/850 mg) IR FDC in fed state
1	Dapagliflozin + Glucophage tablet fasted	5 mg dapagliflozin and 850 mg Glucophage in fasted state
2	Dapagliflozin/metformin IR FDC tablet fasted	dapagliflozin/metformin (5 mg/850 mg) immediate release (IR) FDC in fasted
3	Dapagliflozin + Glucophage tablet fed	5 mg dapagliflozin and 850 mg Glucophage in fed state

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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
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
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
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
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
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

Trial Locations

Locations (1)

Research Site; 🇬🇧 London, United Kingdom