Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN)

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT01192139
• Date of registration: 30/08/2010
• Prospective Registration: No
• Primary sponsor: AstraZeneca
• Public title: Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN)
• Scientific title: Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN) Coadministered to Healthy Subjects in a Fed Condition
• Date of first enrolment: November 2009
• Target sample size: 30
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01192139
• 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 male and female subjects as determined by no clinically significant deviation
from normal in medical history, physical examination, electrocardiogram (ECG), and
clinical laboratory determinations

- Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive

- Ages 18 to 45, inclusive

Exclusion Criteria:

- Evidence of organ dysfunction or any clinically significant deviation from normal in
physical examination, vital signs, ECG or clinical laboratory determinations beyond
what is consistent with the target population

- Major surgical procedure within 4 weeks prior to randomization

- Positive serology test for human immunodeficiency virus (HIV), hepatitis B virus (HBV)
or hepatitis C virus (HCV)

- Clinically significant history or presence of any of the following conditions: heart,
liver, or kidney disease, neurologic or psychiatric disease

- History of gastrointestinal disease within the past 3 months

- Any clinically significant medical condition that could potentially affect your
participation in the study and/or personal well-being, as judged by the investigator

- Donated blood or blood products to a blood bank, blood transfusion or participated in
a clinical study (except a screening visit) requiring withdrawal of blood within 4
weeks prior to randomization

- Unable to tolerate oral and/or intravenous (IV) medications

- Unable to tolerate the puncturing of veins for drawing of blood

- Known allergy or hypersensitivity to any component of the study medication

- History of any significant drug allergies (such as anaphylaxis or hepatotoxicity)

- Used any prescription drugs or over the counter products to control acid (for example,
Prevacid, Mylanta or Rolaids) within 4 weeks prior to randomization

- Used any other drugs including over the counter medications and herbal preparations
within 1 week prior to randomization

- Taken any investigational drug or placebo (inactive drug) within 4 weeks prior to
randomization



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

Health Condition(s) or Problem(s) studied

Diabetes Mellitus

Intervention(s)

Drug: metformin XR

Drug: saxagliptin + metformin XR (FDC tablet)

Drug: saxagliptin

Primary Outcome(s)

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Metformin AUC(0-inf) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Metformin Cmax [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Saxagliptin Observed Maximum Plasma Concentration (Cmax) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Secondary Outcome(s)

Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities [Time Frame: From Day 1 of Period 1 through Day 3 of Period 3 (study discharge)]

Active Metabolite BMS-510849 T1/2 [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Active Metabolite BMS-510849 Cmax [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Active Metabolite BMS-510849 AUC(0-t) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Metformin T1/2 [Time Frame: Period 1 (before dosing, 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)]

Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf) [Time Frame: Period 1 (samples taken before dosing, and at 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)]

Metformin AUC(0-t) [Time Frame: Period 1 (samples taken before dosing, and at 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)]

Active Metabolite BMS-510849 AUC(0-inf) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Active Metabolite BMS-510849 Tmax [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf]) [Time Frame: Period 1 (before dosing, 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)]

Metformin Tmax [Time Frame: Periods 1, 2, and 3 (before dosing, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs) [Time Frame: AEs: from initiation of study drug administration on Day 1/Period 1 through study discharge Day 3/Period 3. SAEs: from date of written consent until 30 days after discontinuation of dosing or participation in study if last scheduled visit occurred later.]

Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf]) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Saxagliptin Terminal Half-life (T1/2) [Time Frame: Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)]

Secondary ID(s)

CV181-111

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 17/05/2011
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01192139