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

Tracking Information

First Received Date ^ICMJE

August 9, 2012

Last Updated Date

March 28, 2013

Start Date ^ICMJE

August 2012

Primary Completion Date

November 2012 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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 ]

Original Primary Outcome Measures ^ICMJE

Same as current

Change History

Complete list of historical versions of study NCT01662999 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

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

Original Secondary Outcome Measures ^ICMJE

Same as current

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

Brief Summary

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

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 1

Study Design ^ICMJE

Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label

Condition ^ICMJE

Type 2 Diabetes Mellitus

Intervention ^ICMJE

Drug: Saxagliptin
Other Names:
- Onglyza®
- BMS-477118
Drug: Dapagliflozin
Other Name: BMS-512148

Study Arm (s)

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
Interventions:
- Drug: Saxagliptin
- Drug: Dapagliflozin
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
Interventions:
- Drug: Saxagliptin
- Drug: Dapagliflozin
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
Interventions:
- Drug: Saxagliptin
- Drug: Dapagliflozin
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
Interventions:
- Drug: Saxagliptin
- Drug: Dapagliflozin
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
Interventions:
- Drug: Saxagliptin
- Drug: Dapagliflozin
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
Interventions:
- Drug: Saxagliptin
- Drug: Dapagliflozin

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

Completion Date

November 2012

Primary Completion Date

November 2012 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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

Gender

Both

Ages

18 Years to 45 Years

Accepts Healthy Volunteers

Yes

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Location Countries ^ICMJE

United States

Administrative Information

NCT Number ^ICMJE

NCT01662999

Other Study ID Numbers ^ICMJE

CV181-191

Has Data Monitoring Committee

Responsible Party

Bristol-Myers Squibb

Study Sponsor ^ICMJE

Bristol-Myers Squibb

Collaborators ^ICMJE

AstraZeneca

Investigators ^ICMJE

Study Director:

Bristol-Myers Squibb

Information Provided By

Bristol-Myers Squibb

Verification Date

October 2012

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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