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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01535677
• Other study ID #: D1691C00007
• Status: Completed
• Phase: Phase 1
• First received: January 13, 2012
• Last updated: July 8, 2015
• Start date: April 2013
• Est. completion date: July 2013

Study information

• Verified date: July 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin + Glucophage tablet fasted
Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fasted state
• Dapagliflozin/metformin IR FDC tablet fasted
single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fasted state
• Dapagliflozin + Glucophage tablet fed
Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fed state
• Dapagliflozin/metformin IR FDC tablet fed
single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fed state

Locations

Country	Name	City	State
United Kingdom	Research Site	London

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Bristol-Myers Squibb

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve over the time (AUC)	No statistical analysis will be performed	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	Yes
Primary	AUC from time zero to the time of last quantifiable analyte concentration (AUC(0-t))	No statistical analysis will be performed	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	Yes
Primary	Maximum concentration (Cmax)	No statistical analysis will be performed	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	Yes
Secondary	Time to reach maximum analyte concentration (tmax)	No statistical analysis will be performed	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
Secondary	Terminal rate constant (?z)	No statistical analysis will be performed	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
Secondary	Time of last quantifiable analyte concentration (tlast)	No statistical analysis will be performed	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
Secondary	Terminal half-life (t1/2)	No statistical analysis will be performed	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
Secondary	Observed maximum analyte concentration (Cmax)	No statistical analysis will be performed	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
Secondary	Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC)	No statistical analysis will be performed	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
Secondary	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	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
Secondary	Elimination terminal half-life (t1/2)	No statistical analysis will be performed	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
Secondary	Safety profile description in term of Adverse Events	No statistical analysis will be performed	from first dose in treatment period 1 up to 10 days after final dose	Yes
Secondary	Safety profile description in term of Blood Pressure	No statistical analysis will be performed	at screening, once daily during the residential period (5 days each) and up to 10 days after final dose	Yes
Secondary	Safety profile description in term of Physical Examination	No statistical analysis will be performed	at screening, Day -1 and Day 4 at Visits 2 to 5 and up to 10 days after final dose	Yes
Secondary	Safety profile description in term of Electrocardiogram ECG	No statistical analysis will be performed	at screening and up to 10 days after final dose	Yes
Secondary	Safety profile description in term of Heart Rate	No statistical analysis will be performed	at screening, once daily during the residential period (5 days each) and up to 10 days after final dose	Yes
Secondary	Safety profile description in term of Safety Labs	No statistical analysis will be performed	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	Yes

External Links

•   D1691C00007_Clinical_Study_Protocol
•   D1691C00007_CSR_Synopsis