Bioequivalence/Food Effect - Saxa/Dapa Dual Fixed Dose Combination (FDC)

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the bioequivalence (BE) of Saxagliptin and Dapagliflozin from a 2.5-mg Saxagliptin/5-mg Dapagliflozin FDC tablet after oral administration relative to 2.5-mg Saxagliptin and 5-mg Dapagliflozin tablets administered orally together in the fasted state and to demonstrate the BE of Saxagliptin and Dapagliflozin from a 5-mg Saxagliptin/10-mg Dapagliflozin FDC tablet after oral administration relative to 5-mg Saxagliptin and 10-mg Dapagliflozin tablets administered orally together in the fasted state. Demonstrating bioequivalence refers to showing that the FDC tablet and co-administration of the individual components yield similar blood levels/concentrations of the drug and are handled by the body similarly.

Detailed Description
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Primary Purpose: This study is designed to demonstrate the bioequivalence of Saxagliptin and Dapagliflozin from a FDC tablet after oral administration relative to Saxagliptin and Dapagliflozin tablets administered orally together in the fasted and fed state

Official Title
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A Bioequivalence Study of 2.5-mg Saxagliptin/5-mg Dapagliflozin and 5-mg Saxagliptin/10-mg Dapagliflozin Fixed Dose Combination Tablets Relative to Coadministration of Their Respective Individual Components in Healthy Subjects and a Characterization of the Effect of Food on the Fixed Dose Combination Tablets

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Saxagliptin
* Drug: Dapagliflozin
* Drug: Saxagliptin/Dapagliflozin FDC


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination (PE), vital signs, 12-lead ECG, and clinical laboratory determinations Body mass index (BMI) of 18.5 to 30 kg/m(2) Men and women, ages 18 to 50 years Women of childbearing potential must use acceptable methods of highly effective birth control Exclusion Criteria: Any significant acute or chronic medical illness Current or recent gastrointestinal disease Any major surgery within 4 weeks of study drug administration History of chronic or recurrent urinary tract infection for females History of glucose intolerance or diabetes mellitus History of allergies or adverse reactions to Dipeptidyl peptidase-IV (DPP4) or Sodium-glucose cotransporter (SGLT) inhibitors Prior exposure to Saxagliptin or Dapagliflozin or related drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment A: Saxagliptin 2.5mg+Dapagliflozin 5mg; Fasting<br>Saxagliptin 2.5 mg tablet and Dapagliflozin 5 mg tablet single dose orally on Day 1 in one of 3 periods | Drug: Saxagliptin<br> <br> * Other names: BMS-477118;Drug: Dapagliflozin<br> <br> * Other names: BMS-512148;|
| Other: Treatment B: Saxagliptin 2.5mg/Dapagliflozin 5mg FDC; Fasting<br>Saxagliptin 2.5 mg/Dapagliflozin 5 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods | Drug: Saxagliptin/Dapagliflozin FDC<br> <br> * Other names: BMS-986098;|
| Other: Treatment C: Saxagliptin 2.5mg/Dapagliflozin 5mg FDC; Fed<br>Saxagliptin 2.5 mg/Dapagliflozin 5 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods | Drug: Saxagliptin/Dapagliflozin FDC<br> <br> * Other names: BMS-986098;|
| Other: Treatment D: Saxagliptin 5mg+Dapagliflozin 10mg; Fasting<br>Saxagliptin 5 mg tablet and Dapagliflozin 10 mg tablet single dose orally for on Day 1 in one of 3 periods | Drug: Saxagliptin<br> <br> * Other names: BMS-477118;Drug: Dapagliflozin<br> <br> * Other names: BMS-512148;|
| Other: Treatment E: Saxagliptin 5mg/Dapagliflozin 10mg FDC; Fasting<br>Saxagliptin 5 mg/Dapagliflozin 10 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods | Drug: Saxagliptin/Dapagliflozin FDC<br> <br> * Other names: BMS-986098;|
| Other: Treatment F: Saxagliptin 5mg/Dapagliflozin 10mg FDC; Fed<br>Saxagliptin 5 mg/Dapagliflozin 10 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods | Drug: Saxagliptin/Dapagliflozin FDC<br> <br> * Other names: BMS-986098;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) for Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 
| Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [(AUC(0-T)] for Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 
| Area under the concentration-time curve from time zero extrapolated to infinite time [(AUC(INF)] for Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax for 5-hydroxy (OH) Saxagliptin |  | 54 time points up to 15 days | 
| AUC(0-T) for 5-hydroxy (OH) Saxagliptin |  | 54 time points up to 15 days | 
| AUC(INF) for 5-hydroxy (OH) Saxagliptin |  | 54 time points up to 15 days | 
| Time of maximum observed plasma concentration (Tmax) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 
| Percent of AUC extrapolated from last quantifiable concentration to infinity (pAUCe) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 
| Half life (T HALF) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 
| Terminal disposition rate constant (Lambda) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 
| Time point where log-linear elimination begins (TLIN) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 
| Time at which the last concentration occurred that is above the lower limit of quantitation (LQCT) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin |  | 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days | 
| Safety measured by the occurrence of deaths, adverse events (AEs), serious adverse events (SAEs), results of clinical laboratory tests, vital sign measurements, physical examination findings, and 12-lead electrocardiogram (ECG) results |  | Approximately up to 16 days |