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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01662999
• Date of registration: 09/08/2012
• Prospective Registration: No
• Primary sponsor: AstraZeneca
• Public title: Drug Interaction Study of Saxagliptin in Combination With Dapagliflozin in Healthy Participants
• Scientific 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
• Date of first enrolment: August 2012
• Target sample size: 42
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01662999
• Study type: Interventional
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 45 Years
Gender: All

Health Condition(s) or Problem(s) studied

Type 2 Diabetes Mellitus

Intervention(s)

Drug: Dapagliflozin

Drug: Saxagliptin

Primary Outcome(s)

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0 h to 60 h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

Secondary Outcome(s)

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

Mean Change From Baseline in Temperature - Safety Population [Time Frame: Baseline to Day 1 in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

Number of Participants With Change From Baseline in ECG Interval - Safety Population [Time Frame: Baseline to end of study (16 days)]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

Plasma Apparent Clearance (CLT/F) of a Single Dose of Dapagliflozin Versus CLT/F of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population [Time Frame: Day 1 (0h to 60h post dose) in each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

Mean Change From Baseline in Heart Rate - Safety Population [Time Frame: Baseline to Day 1 in each period]

Mean Change From Baseline in Systolic and Diastolic Blood Pressure - Safety Population [Time Frame: Baseline to Day 1 of each period]

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 [Time Frame: Day 1 (0h to 60h post dose) in each period]

Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population [Time Frame: Day 1 to end of study (16 days)]

Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population [Time Frame: Baseline to Day 1 in each period]

Number of Participants With Marked Hematology Laboratory Abnormalities - Safety Population [Time Frame: Baseline to Day 1 of each period]

Mean Change From Baseline in Respiration Rate - Safety Population [Time Frame: Baseline to Day 1 in each period]

Number of Participants With Marked Urinalysis Laboratory Abnormalities - Safety Population [Time Frame: Baseline to Day 1 of each period]

Secondary ID(s)

CV181-191

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 23/12/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01662999