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

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Saxagliptin; Drug: Saxagliptin/Dapagliflozin FDC; Drug: Dapagliflozin

• Registration Number: NCT02060201
• Lead Sponsor: AstraZeneca

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

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-02-10
• Study First Submitted QC: 2014-02-10
• Study First Posted: 2014-02-11
• Primary Completion: 2014-05
• Study Completion: 2014-05
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-09
• Last Update Posted: 2015-06-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment A: Saxagliptin 2.5mg+Dapagliflozin 5mg; Fasting	Saxagliptin	Saxagliptin 2.5 mg tablet and Dapagliflozin 5 mg tablet single dose orally on Day 1 in one of 3 periods
Treatment B: Saxagliptin 2.5mg/Dapagliflozin 5mg FDC; Fasting	Saxagliptin/Dapagliflozin FDC	Saxagliptin 2.5 mg/Dapagliflozin 5 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods
Treatment C: Saxagliptin 2.5mg/Dapagliflozin 5mg FDC; Fed	Saxagliptin/Dapagliflozin FDC	Saxagliptin 2.5 mg/Dapagliflozin 5 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods
Treatment E: Saxagliptin 5mg/Dapagliflozin 10mg FDC; Fasting	Saxagliptin/Dapagliflozin FDC	Saxagliptin 5 mg/Dapagliflozin 10 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods
Treatment F: Saxagliptin 5mg/Dapagliflozin 10mg FDC; Fed	Saxagliptin/Dapagliflozin FDC	Saxagliptin 5 mg/Dapagliflozin 10 mg fixed dose combination tablet single dose orally on Day 1 in one of 3 periods
Treatment A: Saxagliptin 2.5mg+Dapagliflozin 5mg; Fasting	Dapagliflozin	Saxagliptin 2.5 mg tablet and Dapagliflozin 5 mg tablet single dose orally on Day 1 in one of 3 periods
Treatment D: Saxagliptin 5mg+Dapagliflozin 10mg; Fasting	Saxagliptin	Saxagliptin 5 mg tablet and Dapagliflozin 10 mg tablet single dose orally for on Day 1 in one of 3 periods
Treatment D: Saxagliptin 5mg+Dapagliflozin 10mg; Fasting	Dapagliflozin	Saxagliptin 5 mg tablet and Dapagliflozin 10 mg tablet single dose orally for on Day 1 in one of 3 periods

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Cmax 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
AUC(0-T) 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
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
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 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