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

Bioavailability Study of Two Prototype Fixed Dose Combination (FDC) Formulations of 10 mg Dapagliflozin and 1000 mg Metformin Extended Release (XR) Tablet Relative to Dapagliflozin 10 mg Tablet and Glucophage® XR 2 X 500 mg Tablets Coadministered to Healthy Subjects in a Fasted State

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus (T2DM)
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Metformin XR; Drug: Glucophage

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: FDC of dapagliflozin/metformin XR	Drug: Dapagliflozin; Tablets, Oral, 10 mg, Single Dose; Drug: Metformin XR; Tablets, Oral, 1000 mg, Single Dose
Other: FDC of dapagliflozin/reduced mass metformin XR	Drug: Dapagliflozin; Tablets, Oral, 10 mg, Single Dose; Drug: Metformin XR; Tablets, Oral, 1000 mg, Single Dose
Other: dapagliflozin and Glucophage® XR	Drug: Dapagliflozin; Tablets, Oral, 10 mg, Single Dose; Drug: Glucophage; Tablets, Oral, 1000 mg, Single Dose; Other Names: Glucophage™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood samples to measure the pharmacokinetic parameters Cmax and AUC for the combination products versus each investigational product alone	48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability measures (adverse events, physical exams, vital signs, ECGs, and clinical laboratory assessments)	15 timepoints in 48 hours time interval

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• MB102-065_redacted_CSR_synopsis

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: October 26, 2009
• First Submitted That Met QC Criteria: October 26, 2009
• First Posted (Estimate): October 27, 2009

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin; Metformin
• Other Study ID Numbers: MB102-065