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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Saxagliptin; Drug: Saxagliptin/Dapagliflozin FDC

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 Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Treatment A: Saxagliptin 2.5mg+Dapagliflozin 5mg; Fasting; Saxagliptin 2.5 mg tablet and Dapagliflozin 5 mg tablet single dose orally on Day 1 in one of 3 periods	Drug: Dapagliflozin; Other Names: BMS-512148; Forxiga®; Farxiga®; Drug: Saxagliptin; Other Names: BMS-477118; Onglyza®
OTHER: Treatment B: Saxagliptin 2.5mg/Dapagliflozin 5mg FDC; Fasting; 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; Other Names: BMS-986098
OTHER: Treatment C: Saxagliptin 2.5mg/Dapagliflozin 5mg FDC; Fed; 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; Other Names: BMS-986098
OTHER: Treatment D: Saxagliptin 5mg+Dapagliflozin 10mg; Fasting; Saxagliptin 5 mg tablet and Dapagliflozin 10 mg tablet single dose orally for on Day 1 in one of 3 periods	Drug: Dapagliflozin; Other Names: BMS-512148; Forxiga®; Farxiga®; Drug: Saxagliptin; Other Names: BMS-477118; Onglyza®
OTHER: Treatment E: Saxagliptin 5mg/Dapagliflozin 10mg FDC; Fasting; 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; Other Names: BMS-986098
OTHER: Treatment F: Saxagliptin 5mg/Dapagliflozin 10mg FDC; Fed; 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; Other Names: BMS-986098

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): May 1, 2014

Study Registration Dates

• First Submitted: February 10, 2014
• First Submitted That Met QC Criteria: February 10, 2014
• First Posted (ESTIMATE): February 11, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): June 10, 2015
• Last Update Submitted That Met QC Criteria: June 9, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Saxagliptin
• Other Study ID Numbers: CV181-341; 118,840 (OTHER: IND Number)