Clinical trial NCT01874080: Bioequivalence Study
Official title: Bioequivalence Study of the Fixed Dosed 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 Dosed Combination Tablet Manufactured in Mt. Vernon, Indiana and Bioequivalence Study of the Fixed Dosed 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 Dosed Combination Tablet Manufactured in Mt. Vernon, Indiana Administered to Healthy Subjects Under Fed Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2013-06-10
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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

Eligibility criteria: 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)

Primary outcomes:
measure: 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)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: 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)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: 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)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: 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)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: 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)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: 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)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
Secondary outcomes:
measure: Time to maximum observed plasma concentration (Tmax) for Saxagliptin and Metformin and for 5-OH Saxagliptin (Treatments A, B, C, and D)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: Terminal half life (T-HALF) for Saxagliptin and Metformin and for 5-OH Saxagliptin (Treatments A, B, C, and D)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: Cmax for 5-OH Saxagliptin (Treatments A, B, C, and D)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: AUC(0-T) for 5-OH Saxagliptin (Treatments A, B, C, and D)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: AUC(INF) for 5-OH Saxagliptin (Treatments A, B, C, and D)
timeFrame: 19 time points up to Day 3 of Periods 1 and 2
measure: Safety assessments based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests
timeFrame: Up to Day 3 of Periods 1 and 2 and up to 30 days post discontinuation of dosing
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: Icon Development Solutions
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: