Bioequivalence Study

Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01874080
• Other study ID #: CV181-208
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2013
• Last updated: April 21, 2015
• Start date: June 2013
• Est. completion date: July 2013

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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 information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes

Intervention

Drug:
• Saxagliptin/Metformin

Locations

Country	Name	City	State
United States	Icon Development Solutions	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Cmax=Maximum observed plasma concentration; CI=Confidence interval; FDC=Fixed dosed combination; XR=Extended release	19 time points up to Day 3 of Periods 1 and 2	No
Primary	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)	AUC(0-T)=Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration	19 time points up to Day 3 of Periods 1 and 2	No
Primary	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)	AUC(INF)=Area under the plasma concentration-time curve from time zero extrapolated to infinity	19 time points up to Day 3 of Periods 1 and 2	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Cmax for 5-OH Saxagliptin (Treatments A, B, C, and D)		19 time points up to Day 3 of Periods 1 and 2	No
Secondary	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	No
Secondary	AUC(INF) for 5-OH Saxagliptin (Treatments A, B, C, and D)		19 time points up to Day 3 of Periods 1 and 2	No
Secondary	Safety assessments based on adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests	Parameters will include: Serious adverse events; Deaths; Adverse events leading to discontinuation; Number of subjects with potentially clinically significant changes in vital signs, electrocardiograms (ECGs) or safety laboratory findings defined as meeting marked abnormality criteria	Up to Day 3 of Periods 1 and 2 and up to 30 days post discontinuation of dosing	Yes

External Links

•   BMS Clinical Trials Disclosure
•   CV181208_CSR_Synopsis
•   FDA Safety Alerts and Recalls
•   Investigator Inquiry form