Clinical trial NCT01662999: Drug Interaction Study of Saxagliptin in Combination With Dapagliflozin in Healthy Participants
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2012-08-13
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

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


Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Day 1 (0 h to 60 h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
Secondary outcomes:
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: Plasma Apparent Clearance (CLT/F) of a Single Dose of Dapagliflozin Versus CLT/F of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: 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
timeFrame: Day 1 (0h to 60h post dose) in each period
measure: Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population
timeFrame: Day 1 to end of study (16 days)
measure: Number of Participants With Marked Hematology Laboratory Abnormalities - Safety Population
timeFrame: Baseline to Day 1 of each period
measure: Mean Change From Baseline in Systolic and Diastolic Blood Pressure - Safety Population
timeFrame: Baseline to Day 1 of each period
measure: Mean Change From Baseline in Heart Rate - Safety Population
timeFrame: Baseline to Day 1 in each period
measure: Mean Change From Baseline in Respiration Rate - Safety Population
timeFrame: Baseline to Day 1 in each period
measure: Mean Change From Baseline in Temperature - Safety Population
timeFrame: Baseline to Day 1 in each period
measure: Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population
timeFrame: Baseline to Day 1 in each period
measure: Number of Participants With Marked Urinalysis Laboratory Abnormalities - Safety Population
timeFrame: Baseline to Day 1 of each period
measure: Number of Participants With Change From Baseline in ECG Interval - Safety Population
timeFrame: Baseline to end of study (16 days)
Other outcomes:
Locations:
city: Omaha
country: United States
facility: Icon Clinical Pharmacology
state: Nebraska
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Vakkalagadda B, Lubin S, Reynolds L, Liang D, Marion AS, LaCreta F, Boulton DW. Lack of a Pharmacokinetic Interaction Between Saxagliptin and Dapagliflozin in Healthy Subjects: A Randomized Crossover Study. Clin Ther. 2016 Aug;38(8):1890-9. doi: 10.1016/j.clinthera.2016.07.005. Epub 2016 Aug 2.