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

Condition(s) targeted: Type 2 Diabetes Mellitus

Intervention: Saxagliptin (Drug); Dapagliflozin (Drug); Saxagliptin/Dapagliflozin FDC (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb

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.

Official title: 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

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

Primary outcome:

Maximum observed plasma concentration (Cmax) for Saxagliptin and Dapagliflozin

Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [(AUC(0-T)] for Saxagliptin and Dapagliflozin

Area under the concentration-time curve from time zero extrapolated to infinite time [(AUC(INF)] for Saxagliptin and Dapagliflozin

Secondary outcome:

Cmax for 5-hydroxy (OH) Saxagliptin

AUC(0-T) for 5-hydroxy (OH) Saxagliptin

AUC(INF) for 5-hydroxy (OH) Saxagliptin

Time of maximum observed plasma concentration (Tmax) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin

Percent of AUC extrapolated from last quantifiable concentration to infinity (pAUCe) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin

Half life (T HALF) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin

Terminal disposition rate constant (Lambda) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin

Time point where log-linear elimination begins (TLIN) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin

Time at which the last concentration occurred that is above the lower limit of quantitation (LQCT) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin

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

Detailed description: 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

Minimum age: 18 Years. Maximum age: 50 Years. Gender(s): Both.

Criteria:

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

CSR Synopsis

Starting date: February 2014
Last updated: June 9, 2015