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

Primary Purpose

Type 2 Diabetes Mellitus

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

Dapagliflozin + Glucophage tablet fasted

Dapagliflozin/metformin IR FDC tablet fasted

Dapagliflozin + Glucophage tablet fed

Dapagliflozin/metformin IR FDC tablet fed

About this trial

This is an interventional basic science trial for Type 2 Diabetes Mellitus focused on measuring Phase 1, healthy volunteers, cross-over study, Bioavailability, Bioequivalence, Cmax, tmax, AUC, AUC(0-t), λz, tlast

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Research Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Arm Description

5 mg dapagliflozin and 850 mg Glucophage in fasted state

dapagliflozin/metformin (5 mg/850 mg) immediate release (IR) FDC in fasted

5 mg dapagliflozin and 850 mg Glucophage in fed state

dapagliflozin/metformin (5 mg/850 mg) IR FDC in fed state

Outcomes

Primary Outcome Measures

Area under the curve over the time (AUC)

No statistical analysis will be performed

AUC from time zero to the time of last quantifiable analyte concentration (AUC(0-t))

No statistical analysis will be performed

Maximum concentration (Cmax)

No statistical analysis will be performed

Secondary Outcome Measures

Time to reach maximum analyte concentration (tmax)

No statistical analysis will be performed

Terminal rate constant (λz)

No statistical analysis will be performed

Time of last quantifiable analyte concentration (tlast)

No statistical analysis will be performed

Terminal half-life (t1/2)

No statistical analysis will be performed

Observed maximum analyte concentration (Cmax)

No statistical analysis will be performed

Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)

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))

No statistical analysis will be performed

Elimination terminal half-life (t1/2)

No statistical analysis will be performed

Safety profile description in term of Adverse Events

No statistical analysis will be performed

Safety profile description in term of Blood Pressure

No statistical analysis will be performed

Safety profile description in term of Physical Examination

No statistical analysis will be performed

Safety profile description in term of Electrocardiogram ECG

No statistical analysis will be performed

Safety profile description in term of Heart Rate

No statistical analysis will be performed

Safety profile description in term of Safety Labs

No statistical analysis will be performed

Full Information

NCT ID

NCT01535677

First Posted

January 13, 2012

Last Updated

July 8, 2015

Sponsor

AstraZeneca

Collaborators

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT01535677

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2015

Overall Recruitment Status

Completed

Study Start Date

April 2013 (undefined)

Primary Completion Date

July 2013 (Actual)

Study Completion Date

July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

Bristol-Myers Squibb

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes Mellitus

Keywords

Phase 1, healthy volunteers, cross-over study, Bioavailability, Bioequivalence, Cmax, tmax, AUC, AUC(0-t), λz, tlast

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

71 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

5 mg dapagliflozin and 850 mg Glucophage in fasted state

Arm Title

Arm Type

Experimental

Arm Description

dapagliflozin/metformin (5 mg/850 mg) immediate release (IR) FDC in fasted

Arm Title

Arm Type

Experimental

Arm Description

5 mg dapagliflozin and 850 mg Glucophage in fed state

Arm Title

Arm Type

Experimental

Arm Description

dapagliflozin/metformin (5 mg/850 mg) IR FDC in fed state

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin + Glucophage tablet fasted

Intervention Description

Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fasted state

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin/metformin IR FDC tablet fasted

Intervention Description

single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fasted state

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin + Glucophage tablet fed

Intervention Description

Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fed state

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin/metformin IR FDC tablet fed

Intervention Description

single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fed state

Primary Outcome Measure Information:

Title

Area under the curve over the time (AUC)

Description

No statistical analysis will be performed

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

Title

AUC from time zero to the time of last quantifiable analyte concentration (AUC(0-t))

Description

No statistical analysis will be performed

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

Title

Maximum concentration (Cmax)

Description

No statistical analysis will be performed

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

Secondary Outcome Measure Information:

Title

Time to reach maximum analyte concentration (tmax)

Description

No statistical analysis will be performed

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

Title

Terminal rate constant (λz)

Description

No statistical analysis will be performed

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

Title

Time of last quantifiable analyte concentration (tlast)

Description

No statistical analysis will be performed

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

Title

Terminal half-life (t1/2)

Description

No statistical analysis will be performed

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

Title

Observed maximum analyte concentration (Cmax)

Description

No statistical analysis will be performed

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

Title

Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)

Description

No statistical analysis will be performed

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

Title

Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUC(0 t))

Description

No statistical analysis will be performed

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

Title

Elimination terminal half-life (t1/2)

Description

No statistical analysis will be performed

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

Title

Safety profile description in term of Adverse Events

Description

No statistical analysis will be performed

Time Frame

from first dose in treatment period 1 up to 10 days after final dose

Title

Safety profile description in term of Blood Pressure

Description

No statistical analysis will be performed

Time Frame

at screening, once daily during the residential period (5 days each) and up to 10 days after final dose

Title

Safety profile description in term of Physical Examination

Description

No statistical analysis will be performed

Time Frame

at screening, Day -1 and Day 4 at Visits 2 to 5 and up to 10 days after final dose

Title

Safety profile description in term of Electrocardiogram ECG

Description

No statistical analysis will be performed

Time Frame

at screening and up to 10 days after final dose

Title

Safety profile description in term of Heart Rate

Description

No statistical analysis will be performed

Time Frame

at screening, once daily during the residential period (5 days each) and up to 10 days after final dose

Title

Safety profile description in term of Safety Labs

Description

No statistical analysis will be performed

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Eva Johnsson, MD

Organizational Affiliation

AstraZeneca Research and Development SE-431 83 Mölndal Sweden

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Saeed Kahn, MBBS

Organizational Affiliation

Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen St, London SE1 1YR

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Mirjana Kujacic, PHD

Organizational Affiliation

AstraZeneca Research and DevelopmentSE-431 83 Mölndal Sweden

Official's Role

Study Chair

Facility Information:

Facility Name

Research Site

City

London

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

26048185

Citation

Chang M, Liu X, Cui D, Liang D, LaCreta F, Griffen SC, Lubin S, Quamina-Edghill D, Boulton DW. Bioequivalence, Food Effect, and Steady-State Assessment of Dapagliflozin/Metformin Extended-release Fixed-dose Combination Tablets Relative to Single-component Dapagliflozin and Metformin Extended-release Tablets in Healthy Subjects. Clin Ther. 2015 Jul 1;37(7):1517-28. doi: 10.1016/j.clinthera.2015.05.004. Epub 2015 Jun 3.

Results Reference

result

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1195&filename=D1691C00007_CSR_Synopsis.pdf

Description

D1691C00007_CSR_Synopsis

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=1195&filename=D1691C00007_Clinical_Study_Protocol_Redacted.pdf

Description

D1691C00007_Clinical_Study_Protocol

Learn more about this trial

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

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