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

Condition(s) targeted: Type 2 Diabetes Mellitus

Intervention: Saxagliptin (Drug); Dapagliflozin (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb

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

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

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

Primary outcome:

Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin From a Single Dose of Dapagliflozin Versus Cmax of Dapagliflozin From Co-administered Saxagliptin Plus Dapagliflozin - Pharmacokinetic Evaluable Population

Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity [AUC(INF)] of Dapagliflozin From a Single Dose of Dapagliflozin Versus AUC (INF) of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population

Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus AUC(0-T) for Dapagliflozin When Co-administered With 5 mg Saxagliptin

Maximum Observed Concentration (Cmax) of a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population

AUC(0-T) of Saxagliptin From Single Dose 5 mg Saxagliptin Versus AUC(0-T) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population

AUC(INF) of Saxagliptin From a Single Dose of 5 mg Saxagliptin Versus AUC(INF) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population

Secondary outcome:

Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus Tmax of Dapagliflozin When Co-administered With 5 mg Saxagliptin - PK Evaluable Population

Half-life (T-HALF) of Dapagliflozin From a Single Dose of Dapagliflozin Versus T-Half of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population

Plasma Apparent Clearance (CLT/F) of a Single Dose of Dapagliflozin Versus CLT/F of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population

Cmax of 5-Hydroxy (5-OH) Saxagliptin From a Single Dose Saxagliptin Versus Cmax of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population

AUC(0-T) of 5-OH Saxagliptin From Single Dose Saxagliptin Versus AUC(0-T) of 5-OH From Saxagliptin Co-administered With Dapagliflozin - PK Evaluable Population

AUC(INF) of 5-OH Saxagliptin From a Single Dose Saxagliptin Versus AUC(INF) of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population

Cmax of the Saxagliptin Total Active Moiety From a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population

AUC(INF) and AUC(0-T) of the Saxagliptin Total Active Moiety From a Single Dose 5 mg Saxagliptin Versus AUC(INF) and AUC(0-T) of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population

Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population

Half-life (T-HALF) of Saxagliptin, and 5-OH Saxagliptin From Single Dose 5 mg Saxagliptin Versus T-HALF of Saxagliptin and 5-OH From Co-administered Saxagliptin With 10 mg Dapagliflozin - PK Evaluable Population

Metabolite to Parent Molar Ratios (MR) of Cmax, AUC(INF), and AUC(0-T) of 5-OH Saxagliptin and Saxagliptin From a Single Dose 5 mg Saxagliptin Versus MR of Saxagliptin and 5-OH When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable

Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population

Number of Participants With Marked Hematology Laboratory Abnormalities - Safety Population

Mean Change From Baseline in Systolic and Diastolic Blood Pressure - Safety Population

Mean Change From Baseline in Heart Rate - Safety Population

Mean Change From Baseline in Respiration Rate - Safety Population

Mean Change From Baseline in Temperature - Safety Population

Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population

Number of Participants With Marked Urinalysis Laboratory Abnormalities - Safety Population

Number of Participants With Change From Baseline in ECG Interval - Safety Population

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Healthy subjects as determined by no clinically significant deviation from normal in

medical history, Physical Examination, 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

Icon Clinical Pharmacology, Omaha, Nebraska 68154, United States

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Starting date: August 2012
Last updated: April 21, 2015