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

Purpose

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.

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: Dapagliflozin + Glucophage tablet fasted Drug: Dapagliflozin/metformin IR FDC tablet fasted Drug: Dapagliflozin + Glucophage tablet fed Drug: Dapagliflozin/metformin IR FDC tablet fed	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	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

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
No statistical analysis will be performed

Secondary Outcome Measures:

Time to reach maximum analyte concentration (tmax) [ 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 ] [ Designated as safety issue: No ]
No statistical analysis will be performed
Terminal rate constant (λz) [ 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 ] [ Designated as safety issue: No ]
No statistical analysis will be performed
Time of last quantifiable analyte concentration (tlast) [ 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 ] [ Designated as safety issue: No ]
No statistical analysis will be performed
Terminal half-life (t1/2) [ 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 ] [ Designated as safety issue: No ]
No statistical analysis will be performed
Observed maximum analyte 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 ] [ Designated as safety issue: No ]
No statistical analysis will be performed
Area under the plasma concentration-time curve from time zero extrapolated to infinity (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 ] [ Designated as safety issue: No ]
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)) [ 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 ] [ Designated as safety issue: No ]
No statistical analysis will be performed
Elimination terminal half-life (t1/2) [ 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 ] [ Designated as safety issue: No ]
No statistical analysis will be performed
Safety profile description in term of Adverse Events [ Time Frame: from first dose in treatment period 1 up to 10 days after final dose ] [ Designated as safety issue: Yes ]
No statistical analysis will be performed
Safety profile description in term of Blood Pressure [ Time Frame: at screening, once daily during the residential period (5 days each) and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
No statistical analysis will be performed
Safety profile description in term of Physical Examination [ Time Frame: at screening, Day -1 and Day 4 at Visits 2 to 5 and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
No statistical analysis will be performed
Safety profile description in term of Electrocardiogram ECG [ Time Frame: at screening and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
No statistical analysis will be performed
Safety profile description in term of Heart Rate [ Time Frame: at screening, once daily during the residential period (5 days each) and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
No statistical analysis will be performed
Safety profile description in term of Safety Labs [ Time Frame: 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 ] [ Designated as safety issue: Yes ]
No statistical analysis will be performed

Estimated Enrollment:	36
Study Start Date:	April 2013
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 5 mg dapagliflozin and 850 mg Glucophage in fasted state	Drug: Dapagliflozin + Glucophage tablet fasted Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fasted state
Experimental: 2 dapagliflozin/metformin (5 mg/850 mg) immediate release (IR) FDC in fasted	Drug: Dapagliflozin/metformin IR FDC tablet fasted single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fasted state
Experimental: 3 5 mg dapagliflozin and 850 mg Glucophage in fed state	Drug: Dapagliflozin + Glucophage tablet fed Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fed state
Experimental: 4 dapagliflozin/metformin (5 mg/850 mg) IR FDC in fed state	Drug: Dapagliflozin/metformin IR FDC tablet fed single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fed state

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

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01535677

Contacts

Contact: AstraZeneca Clinical Study Information	800-236-9933	information.center@astrazeneca.com
Contact: Quintiles London (QLON), London, England	+44 0800 634 1132

Locations

United Kingdom
	Recruiting
London, United Kingdom

Sponsors and Collaborators

AstraZeneca

Bristol-Myers Squibb

Investigators

Study Director:	Eva Johnsson, MD	AstraZeneca Research and Development SE-431 83 Mölndal Sweden
Principal Investigator:	Saeed Kahn, MBBS	Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen St, London SE1 1YR
Study Chair:	Mirjana Kujacic, PHD	AstraZeneca Research and DevelopmentSE-431 83 Mölndal Sweden

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01535677 History of Changes
Other Study ID Numbers:	D1691C00007
Study First Received:	January 13, 2012
Last Updated:	April 25, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:

Phase 1
healthy volunteers
cross-over study
Bioavailability
Bioequivalence
Cmax

tmax
AUC
AUC(0-t)
λz
tlast

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 18, 2013