Diabetes
Conditions
Brief summary
The purpose of this study is to determine if tablets manufactured at different sites have the same bioavailability, that is yield similar blood levels/concentrations of the drugs and are handled by the body similarly
Detailed description
Primary Purpose: Other: Protocol designed to demonstrate the bioequivalence of the fixed dose combination of 5 mg Saxagliptin and 1000 mg Metformin Extended Release Tablet manufactured in Mt. Vernon, Indiana and Humacao, Puerto Rico relative to the fixed dose combination tablet manufactured in Mt. Vernon, Indiana and the bioequivalence of the fixed dose combination of 5 mg Saxagliptin and 500 mg Metformin Extended Release Tablet manufactured in Mt. Vernon, Indiana and Humacao, Puerto Rico relative to the fixed dose combination tablet manufactured in Mt. Vernon, Indiana in healthy human subjects under fed conditions
Interventions
DRUGSaxagliptin/Metformin
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female subjects, 18-45 years of age * Body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive * Women must have a negative serum or urine pregnancy test within 24 hours prior to the start of investigational product
Exclusion criteria
* Any significant acute or chronic medical illness * Estimated creatinine clearance of \<60 mL/min as calculated using the Modification of Diet in Renal Disease method Current or recent (within 3 months of study drug administration) * Gastrointestinal (GI) disease that could affect the absorption of study drug * Inability to tolerate oral medication * History of allergies or adverse reactions to DPP4 inhibitors or Metformin or related compounds * Current smoker or recent (within 6 months of study drug administration) history of regular tobacco use (positive cotinine test)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Point estimates and 90% CIs for the ratio of geometric means for AUC(0-T) for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) | 19 time points up to Day 3 of Periods 1 and 2 | — |
| Point estimates and 90% CIs for the ratio of geometric means for Cmax for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) | 19 time points up to Day 3 of Periods 1 and 2 | Cmax=Maximum observed plasma concentration CI=Confidence interval FDC=Fixed dosed combination XR=Extended release |
| Point estimates and 90% CIs for the ratio of geometric means for AUC(0-T) for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) | 19 time points up to Day 3 of Periods 1 and 2 | AUC(0-T)=Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration |
| Point estimates and 90% CIs for the ratio of geometric means for AUC(INF) for Saxagliptin and Metformin in the 5/1000 mg FDC XR (Mt.Vernon/Humacao) and 5/1000 mg FDC XR (Mt. Vernon) | 19 time points up to Day 3 of Periods 1 and 2 | AUC(INF)=Area under the plasma concentration-time curve from time zero extrapolated to infinity |
| Point estimates and 90% CIs for the ratio of geometric means for AUC(INF) for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) | 19 time points up to Day 3 of Periods 1 and 2 | — |
| Point estimates and 90% CIs for the ratio of geometric means for Cmax for Saxagliptin and Metformin in the 5/500 mg FDC XR (Mt. Vernon/Humacao) and 5/500 mg FDC XR (Mt. Vernon) | 19 time points up to Day 3 of Periods 1 and 2 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to maximum observed plasma concentration (Tmax) for Saxagliptin and Metformin and for 5-OH Saxagliptin (Treatments A, B, C, and D) | 19 time points up to Day 3 of Periods 1 and 2 | — |
| Terminal half life (T-HALF) for Saxagliptin and Metformin and for 5-OH Saxagliptin (Treatments A, B, C, and D) | 19 time points up to Day 3 of Periods 1 and 2 | — |
| Cmax for 5-OH Saxagliptin (Treatments A, B, C, and D) | 19 time points up to Day 3 of Periods 1 and 2 | — |
| AUC(0-T) for 5-OH Saxagliptin (Treatments A, B, C, and D) | 19 time points up to Day 3 of Periods 1 and 2 | — |
| AUC(INF) for 5-OH Saxagliptin (Treatments A, B, C, and D) | 19 time points up to Day 3 of Periods 1 and 2 | — |
| Safety assessments based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests | Up to Day 3 of Periods 1 and 2 and up to 30 days post discontinuation of dosing | Parameters will include: 1. Serious adverse events 2. Deaths 3. Adverse events leading to discontinuation 4. Number of subjects with potentially clinically significant changes in vital signs, electrocardiograms (ECGs) or safety laboratory findings defined as meeting marked abnormality criteria |
Countries
United States
Outcome results
None listed