Bioavailability Study of Fixed Dose Combination (FDC) Formulations of Dapagliflozin and Metformin XR Versus Individual Component Coadministered to Healthy Subjects in a Fasted State

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes Mellitus (T2DM)

Treatments: Drug: Metformin XR; Drug: Glucophage; Drug: Dapagliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01002807

MB102-065

Details and patient eligibility

About

To assess the relative bioavailability of dapagliflozin and metformin from the two FDC formulations, comprised of 10 mg dapagliflozin and 1000 mg metformin XR, relative to coadministration of a dapagliflozin 10 mg tablet and 2 x 500 mg Glucophage® XR tablets, in healthy subjects in a fasted state.

Enrollment: 15 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Men and women ages 18 to 45 inclusive
• Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
• Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive. BMI = weight (kg)/ [height (m)]2

Exclusion criteria

• WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last dose of investigational product
• Any significant acute or chronic medical illness
• Current or recent (within 3 months) gastrointestinal disease
• Any major surgery within 4 weeks of study drug administration
• Glucosuria at screening
• Abnormal liver functions tests (ALT, AST or total bilirubin > 10% above ULN)
• Presence of edema on physical exam
• History of diabetes mellitus
• History of heart failure
• History of renal insufficiency
• History of chronic or recurrent UTI (defined as 3 occurrences per year) or UTI in the past 3 months
• History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal mycotic infections
• Estimated creatinine clearance (ClCR) of < 80 mL/min using the Cockcroft Gault formula
• History of allergy or intolerance to metformin or other similar agents

Trial design

15 participants in 3 patient groups

FDC of dapagliflozin/metformin XR

Other group

Treatment:

Drug: Metformin XR

Drug: Dapagliflozin

FDC of dapagliflozin/reduced mass metformin XR

Other group

Treatment:

Drug: Metformin XR

Drug: Dapagliflozin

dapagliflozin and Glucophage® XR

Other group

Treatment:

Drug: Glucophage

Drug: Dapagliflozin