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Bioequivalence Study

Phase 1
Completed
Conditions
Diabetes
Interventions
Drug: Saxagliptin/Metformin
Registration Number
NCT01874080
Lead Sponsor
AstraZeneca
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

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
56
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Arm B: Saxagliptin/Metformin XR FDC (Mt. Vernon)Saxagliptin/MetforminSaxagliptin 5 mg/Metformin 1000 mg (Mt. Vernon) tablet by mouth once daily on Day 1 of Periods 1 and 2
Arm D: Saxagliptin/Metformin XR FDC (Mt. Vernon)Saxagliptin/MetforminSaxagliptin 5 mg/Metformin 500 mg (Mt. Vernon) tablet by mouth once daily Day 1 of Periods 1 and 2
Arm A: Saxagliptin/Metformin XR FDC (Mt. Vernon/Humacao)Saxagliptin/MetforminSaxagliptin 5 mg /Metformin 1000 mg (Mt. Vernon/Humacao) tablet by mouth once daily on Day 1 of Periods 1 and 2
Arm C: Saxagliptin/Metformin XR FDC (Mt. Vernon/Humacao)Saxagliptin/MetforminSaxagliptin 5 mg/Metformin 500 mg (Mt. Vernon/Humacao) tablet by mouth once daily on Day1 of Periods 1 and 2
Primary Outcome Measures
NameTimeMethod
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 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
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 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
Secondary Outcome Measures
NameTimeMethod
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 testsUp 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

Trial Locations

Locations (1)

Icon Development Solutions

🇺🇸

San Antonio, Texas, United States

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