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BE Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin HCl XR Tablet Relative to a 5 mg Saxagliptin (Onglyza™) Tablet and a 500 mg Metformin HCl XR (Glifage® XR Marketed in Brazil by Merck S.A.) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed States

Phase 1
Withdrawn
Conditions
Type 2 Diabetes
Interventions
Drug: Saxagliptin/Metformin XR FDC
Registration Number
NCT01305551
Lead Sponsor
AstraZeneca
Brief Summary

The purpose of this study is to demonstrate the bioequivalence (BE) of Saxagliptin and Metformin from a 5 mg Saxagliptin/500 mg Metformin extended release (XR) fixed dose combination (FDC) tablet relative to 5 mg Onglyza™ and 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) tablets administered together in both the fasted and fed states.

Detailed Description

Primary purpose: To demonstrate the bioequivalence of Saxagliptin and Metformin from a 5 mg Saxagliptin/500 mg Metformin XR FDC tablet relative to 5 mg Onglyza™ and 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) tablets administered together in both the fasted and fed states.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Healthy men and women
  • Women of childbearing potential (WOCBP) who are using acceptable method of contraception
  • Women who are not nursing
Exclusion Criteria
  • History of Gastrointestinal (GI) disease
  • Any GI surgery that could impact study drug absorption
  • History of allergy to drug class or related compounds
  • History of allergy to metformin or other similar acting agents.
  • History of any significant drug allergy.
  • Estimated creatinine clearance (ClCr) < 80 mL/min using Cockcroft-Gault formula

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment A-Saxagliptin+Metformin XRMetformin XR5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fasted state.
Treatment B-Saxagliptin/Metformin XR FDCSaxagliptin/Metformin XR FDC5mg Saxagliptin / 500 mg Metformin XR FDC tablet, once on Day 1 only, administered in the fasted state.
Treatment C-Saxagliptin+Metformin XRMetformin XR5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fed state.
Treatment D-Saxagliptin/Metformin XR FDCSaxagliptin/Metformin XR FDC5mg Saxagliptin / 500 mg Metformin XR FDC tablet, once on Day 1 only, administered in the fed state.
Treatment A-Saxagliptin+Metformin XRSaxagliptin5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fasted state.
Treatment C-Saxagliptin+Metformin XRSaxagliptin5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fed state.
Primary Outcome Measures
NameTimeMethod
Evidence of BE on single-dose pharmacokinetic parameters maximum observed concentration (Cmax) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data.48 hours after dosing
Evidence of BE on single-dose pharmacokinetic parameters time of maximum observed concentration (Tmax) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data.48 hours after dosing
Evidence of BE on single-dose pharmacokinetic parameters area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data.48 hours after dosing
Evidence of BE on single-dose pharmacokinetic parameters (AUC(0-T) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data.48 hours after dosing

Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))

Evidence of BE on single-dose pharmacokinetic parameters half-life (T-HALF) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data.48 hours after dosing
Secondary Outcome Measures
NameTimeMethod
Active metabolite of Saxagliptin, 5-Hydroxy Saxagliptin, from 5 mg Saxagliptin/500 mg Metformin XR FDC tablet & from 5 mg Onglyza administered together with 500 mg Glifage® XR in single-dose fed & fasted state pharmacokinetics in healthy subjects3 days after dosing

Amount of the active metabolite of Saxagliptin, 5-Hydroxy Saxagliptin (BMS-510849), from the 5 mg Saxagliptin/500 mg Metformin XR FDC tablet and from 5 mg Onglyza™ administered together with 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) in single-dose fed and fasted state pharmacokinetics in healthy subjects

Number of Participants with Adverse Events as a Measure of Safety and Tolerability3 days after dosing

Trial Locations

Locations (1)

Local Institution

🇧🇷

Campinas, Sao Paulo, Brazil

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