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Drug Interaction Study of Saxagliptin in Combination With Dapagliflozin in Healthy Participants

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01662999
First received: August 9, 2012
Last updated: March 28, 2013
Last verified: October 2012
History of Changes
  Purpose

The purpose of this study is to evaluate whether the pharmacokinetics (body concentrations/metabolism of the drug) of Saxagliptin and Dapagliflozin are affected when they are administered together


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Single-dose, Open-label, Randomized, 3 Period, 3 Treatment Crossover Study to Evaluate the Pharmacokinetics of Saxagliptin 5 mg and Dapagliflozin 10 mg When Coadministered to Fasted Healthy Subjects

Resource links provided by NLM:

Drug Information available for: Saxagliptin
U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Effect of a single 5-mg oral dose of Saxagliptin on Maximum observed plasma concentration (Cmax) of Dapagliflozin when coadministered with a single 10-mg oral dose of Dapagliflozin and vice versa [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Effect of a single 5-mg oral dose of Saxagliptin on Area under the plasma concentration-time curve from time zero extrapolated to infinity [AUC(INF)] of Dapagliflozin when coadministered with a single 10-mg oral dose of Dapagliflozin and vice versa [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum observed plasma concentration (Cmax) of 5-OH Saxagliptin (the major active metabolite of Saxagliptin) will be derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) of Dapagliflozin, Saxagliptin, and 5-OH Saxagliptin (the major active metabolite of Saxagliptin) will be derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Half-life (T-HALF) of Dapagliflozin, Saxagliptin, and 5-OH Saxagliptin (the major active metabolite of Saxagliptin) will be derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • AUC(0-T) of Dapagliflozin, Saxagliptin, and 5-OH Saxagliptin (the major active metabolite of Saxagliptin) will be derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
    AUC(0-T) = Area under the plasma concentration-time curve from time zero to time of the last quantifiable concentration

  • AUC(INF) of 5-OH Saxagliptin (the major active metabolite of Saxagliptin) will be derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
    AUC(INF) = Area under the plasma concentration-time curve from time zero extrapolated to infinity

  • Apparent oral plasma clearance (CLT/F) of Dapagliflozin and Saxagliptin will be derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Molar ratios of metabolite to parent Cmax (MR_Cmax) of 5-OH Saxagliptin and Saxagliptin derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Molar ratios of metabolite to parent AUC(0-T) [MR_AUC(0-T)] of 5-OH Saxagliptin and Saxagliptin derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Molar ratios of metabolite to parent AUC(INF) [MR_AUC(INF)] of 5-OH Saxagliptin and Saxagliptin derived from plasma concentration versus time data [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) of the total Saxagliptin active moiety (molar summations of Saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin) [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) of the total Saxagliptin active moiety (molar summations of Saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin) [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • AUC(0-T) of the total Saxagliptin active moiety (molar summations of Saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin) [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • AUC(INF) of the total Saxagliptin active moiety (molar summations of Saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin) [ Time Frame: 39 time points up to 3 periods (Approximately up to 16 days) ] [ Designated as safety issue: No ]
  • Safety and tolerability of a single 5-mg dose of Saxagliptin and a single 10-mg dose of Dapagliflozin when administered alone and in combination [ Time Frame: Approximately up to Day 16 ] [ Designated as safety issue: Yes ]

    Based on:

    • Adverse events (AEs), AEs leading to discontinuation from the study, SAEs, and deaths
    • Vital signs
    • 12-lead electrocardiogram (ECG) data
    • Findings on Physical examinations (PEs)
    • Clinical laboratory test results


Enrollment: 42
Study Start Date: August 2012
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A-B-C: Saxagliptin-Dapagliflozin-(Saxagliptin+Dapagliflozin)
Treatment A: Saxagliptin 5mg, Tablet, Oral, Once daily, 1 day in each of 3 periods; Treatment B: Dapagliflozin 10mg, Tablet, Oral, Once daily, 1 day in each of 3 periods; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, Once daily, 1 day in each of 3 periods
 Drug: Saxagliptin
Other Names:
  • Onglyza®
  • BMS-477118
Drug: Dapagliflozin
Other Name: BMS-512148
Experimental: A-C-B: Saxagliptin-(Saxagliptin+Dapagliflozin)-Dapagliflozin
Treatment A: Saxagliptin 5mg, Tablet, Oral, Once daily, 1 day in each of 3 periods; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, Once daily, 1 day in each of 3 periods; Treatment B: Dapagliflozin 10mg, Tablet, Oral, Once daily, 1 day in each of 3 periods
 Drug: Saxagliptin
Other Names:
  • Onglyza®
  • BMS-477118
Drug: Dapagliflozin
Other Name: BMS-512148
Experimental: B-A-C: Dapagliflozin-Saxagliptin-(Saxagliptin+Dapagliflozin)
Treatment B: Dapagliflozin 10mg, Tablet, Oral, Once daily, 1 day in each of 3 periods; Treatment A: Saxagliptin 5mg, Tablet, Oral, Once daily, 1 day in each of 3 periods; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, Once daily, 1 day in each of 3 periods
 Drug: Saxagliptin
Other Names:
  • Onglyza®
  • BMS-477118
Drug: Dapagliflozin
Other Name: BMS-512148
Experimental: B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin
Treatment B: Dapagliflozin 10mg, Tablet, Oral, Once daily, 1 day in each of 3 periods; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, Once daily, 1 day in each of 3 periods; Treatment A: Saxagliptin 5mg, Tablet, Oral, Once daily, 1 day in each of 3 periods
 Drug: Saxagliptin
Other Names:
  • Onglyza®
  • BMS-477118
Drug: Dapagliflozin
Other Name: BMS-512148
Experimental: C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin
Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, Once daily, 1 day in each of 3 periods; Treatment A: Saxagliptin 5mg, Tablet, Oral, Once daily, 1 day in each of 3 periods; Treatment B: Dapagliflozin 10mg, Tablet, Oral, Once daily, 1 day in each of 3 periods
 Drug: Saxagliptin
Other Names:
  • Onglyza®
  • BMS-477118
Drug: Dapagliflozin
Other Name: BMS-512148
Experimental: C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin
Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, Once daily, 1 day in each of 3 periods; Treatment B: Dapagliflozin 10mg, Tablet, Oral, Once daily, 1 day in each of 3 periods; Treatment A: Saxagliptin 5mg, Tablet, Oral, Once daily, 1 day in each of 3 periods
 Drug: Saxagliptin
Other Names:
  • Onglyza®
  • BMS-477118
Drug: Dapagliflozin
Other Name: BMS-512148

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy subjects as determined by no clinically significant deviation from normal in medical history, PE, vital signs, 12-lead ECG, and clinical laboratory determinations
  • Body mass index (BMI) of 18 to 30 kg/m2
  • Men and women, ages 18 to 45 years
  • Women of childbearing potential must use acceptable methods of highly effective birth control

Exclusion Criteria:

  • History of chronic or recurrent urinary tract infection for females
  • History of allergies or adverse reactions to Dipeptidyl peptidase-IV (DPP4) or Sodium-glucose transporter type 2 (SGLT2) inhibitors
  • Any significant acute or chronic medical illness
  • Current or recent gastrointestinal disease
  • Any major surgery within 4 weeks of study drug administration
  • Prior exposure to saxagliptin or dapagliflozin or related drugs
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01662999

Locations
United States, Nebraska
Icon Clinical Pharmacology
Omaha, Nebraska, United States, 68154
Sponsors and Collaborators
Bristol-Myers Squibb
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trial Information  This link exits the ClinicalTrials.gov site
BMS clinical trial educational resource  This link exits the ClinicalTrials.gov site
Investigator Inquiry form  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01662999     History of Changes
Other Study ID Numbers: CV181-191
Study First Received: August 9, 2012
Last Updated: March 28, 2013
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
Dipeptidyl-Peptidase IV Inhibitors
 Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 21, 2013