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

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT02060201
First received: February 10, 2014
Last updated: June 11, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Saxagliptin
Drug: Dapagliflozin
Drug: Saxagliptin/Dapagliflozin FDC
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Maximum observed plasma concentration (Cmax) for Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [(AUC(0-T)] for Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve from time zero extrapolated to infinite time [(AUC(INF)] for Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cmax for 5-hydroxy (OH) Saxagliptin [ Time Frame: 54 time points up to 15 days ] [ Designated as safety issue: No ]
  • AUC(0-T) for 5-hydroxy (OH) Saxagliptin [ Time Frame: 54 time points up to 15 days ] [ Designated as safety issue: No ]
  • AUC(INF) for 5-hydroxy (OH) Saxagliptin [ Time Frame: 54 time points up to 15 days ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]
  • Percent of AUC extrapolated from last quantifiable concentration to infinity (pAUCe) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]
  • Half life (T HALF) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]
  • Terminal disposition rate constant (Lambda) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]
  • Time point where log-linear elimination begins (TLIN) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]
  • Time at which the last concentration occurred that is above the lower limit of quantitation (LQCT) for Saxagliptin, 5-OH Saxagliptin and Dapagliflozin [ Time Frame: 54 time points for Saxagliptin, 5-OH Saxagliptin and 42 time points for Dapagliflozin up to 15 days ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Approximately up to 16 days ] [ Designated as safety issue: Yes ]

Enrollment: 72
Study Start Date: February 2014
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: Saxagliptin
Other Names:
  • Onglyza®
  • BMS-477118
Drug: Dapagliflozin
Other Names:
  • Farxiga®
  • Forxiga®
  • BMS-512148
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 Name: BMS-986098
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 Name: BMS-986098
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: Saxagliptin
Other Names:
  • Onglyza®
  • BMS-477118
Drug: Dapagliflozin
Other Names:
  • Farxiga®
  • Forxiga®
  • BMS-512148
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 Name: BMS-986098
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 Name: BMS-986098

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

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02060201

Sponsors and Collaborators
Bristol-Myers Squibb
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02060201     History of Changes
Other Study ID Numbers: CV181-341
Study First Received: February 10, 2014
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents

ClinicalTrials.gov processed this record on August 01, 2014