Clinical trial NCT02060201: Bioequivalence/Food Effect - Saxa/Dapa Dual Fixed Dose Combination (FDC)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2014-02-11
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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: 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

Eligibility 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

Primary outcomes:
measure: Maximum observed plasma concentration (Cmax) for Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days
measure: Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [(AUC(0-T)] for Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days
measure: Area under the concentration-time curve from time zero extrapolated to infinite time [(AUC(INF)] for Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days
Secondary outcomes:
measure: Cmax for 5-hydroxy (OH) Saxagliptin
timeFrame: 54 time points up to 15 days
measure: AUC(0-T) for 5-hydroxy (OH) Saxagliptin
timeFrame: 54 time points up to 15 days
measure: AUC(INF) for 5-hydroxy (OH) Saxagliptin
timeFrame: 54 time points up to 15 days
measure: Time of maximum observed plasma concentration (Tmax) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days
measure: Percent of AUC extrapolated from last quantifiable concentration to infinity (pAUCe) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days
measure: Half life (T HALF) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days
measure: Terminal disposition rate constant (Lambda) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days
measure: Time point where log-linear elimination begins (TLIN) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days
measure: Time at which the last concentration occurred that is above the lower limit of quantitation (LQCT) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin
timeFrame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days
measure: 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
timeFrame: Approximately up to 16 days
Other outcomes:
Locations:
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: