Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin Hydrochloride (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
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Sponsor
- AstraZeneca
- Locations
- 1
- Primary Endpoint
- 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.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Single Group
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Treatment A-Saxagliptin+Metformin XR
5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fasted state.
Intervention: Saxagliptin (Drug)
Treatment A-Saxagliptin+Metformin XR
5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fasted state.
Intervention: Metformin XR (Drug)
Treatment B-Saxagliptin/Metformin XR FDC
5mg Saxagliptin / 500 mg Metformin XR FDC tablet, once on Day 1 only, administered in the fasted state.
Intervention: Saxagliptin/Metformin XR FDC (Drug)
Treatment C-Saxagliptin+Metformin XR
5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fed state.
Intervention: Saxagliptin (Drug)
Treatment C-Saxagliptin+Metformin XR
5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fed state.
Intervention: Metformin XR (Drug)
Treatment D-Saxagliptin/Metformin XR FDC
5mg Saxagliptin / 500 mg Metformin XR FDC tablet, once on Day 1 only, administered in the fed state.
Intervention: Saxagliptin/Metformin XR FDC (Drug)
Outcomes
Primary Outcomes
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.
Time Frame: 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.
Time Frame: 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.
Time Frame: 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.
Time Frame: 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.
Time Frame: 48 hours after dosing
Secondary Outcomes
- 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 subjects(3 days after dosing)
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(3 days after dosing)