Phase 1
Completed N=30
Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin/1000 mg Metformin XR (Manufactured in Mt Vernon, IN) Relative to 5 mg of Onglyza and 2 × 500 mg Glucophage XR
Source: ClinicalTrials.gov NCT01192152 ↗Enrolled (actual)
30
Serious AEs
0.0%
Results posted
May 2011
Primary outcomePrimary: Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) — 99.45; 105.28 ng*hr/mL
Summary
The purpose of this study is to demonstrate bioequivalence (BE) of a 5 mg saxagliptin/1000 mg metformin extended release (XR) fixed-dose combination (FDC) tablet (manufactured in Mt Vernon, Indiana) relative to a coadministered 5 mg Onglyza tablet (saxagliptin, manufactured in Mt Vernon, Indiana) and two 500 mg Glucophage XR tablets (metformin XR, manufactured in Evansville, Indiana) in the fed state in healthy subjects.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) |
99.45; 105.28 | — |
| PRIMARY Saxagliptin Observed Maximum Plasma Concentration (Cmax) |
25.28; 25.75; 25.75 | — |
| PRIMARY Metformin AUC(0-inf) |
10336.18; 9211.29 | — |
| PRIMARY Metformin Cmax |
1184.07; 1078.67; 979.93 | — |
| SECONDARY Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) |
97.76; 103.34 | — |
| SECONDARY Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau]) |
19.20 | — |
| SECONDARY Saxagliptin Trough (Predose) Plasma Concentration (Cmin) |
0.28 | — |
| SECONDARY Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg) |
4.13 | — |
| SECONDARY Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %) |
611.85 | — |
| SECONDARY Saxagliptin Terminal Half-life (T1/2) |
8.69; 8.85 | — |
| SECONDARY Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf]) |
0.981; 0.982 | — |
| SECONDARY Saxagliptin Time to Achieve the Observed Maximum Plasma Concentration (Tmax) |
1.88; 1.51; 1.35 | — |
| SECONDARY 5-hydroxy Saxagliptin AUC(0-inf) |
298.80; 296.99 | — |
| SECONDARY 5-hydroxy Saxagliptin AUC(0-t) |
293.06; 289.37 | — |
| SECONDARY 5-hydroxy Saxagliptin AUC(0-tau) |
318.47 | — |
| SECONDARY 5-hydroxy Saxagliptin Cmax |
54.69; 51.32; 59.87 | — |
| SECONDARY 5-hydroxy Saxagliptin Cmin |
1.51 | — |
| SECONDARY 5-hydroxy Saxagliptin Cavg |
13.27 | — |
| SECONDARY 5-hydroxy Saxagliptin Fluctuation % |
437.09 | — |
| SECONDARY 5-hydroxy Saxagliptin T1/2 |
13.48; 13.82 | — |
| SECONDARY 5-hydroxy Saxagliptin AUC(0-t)/AUC(0-inf) |
0.975; 0.973 | — |
| SECONDARY 5-hydroxy Saxagliptin Tmax |
2.69; 2.27; 2.05 | — |
| SECONDARY Metformin AUC(0-t) |
9734.38; 8846.36 | — |
| SECONDARY Metformin AUC(0-tau) |
9501.81 | — |
| SECONDARY Metformin Cmin |
105.04 | — |
| SECONDARY Metformin Cavg |
395.91 | — |
| SECONDARY Metformin Fluctuation % |
240.06 | — |
| SECONDARY Metformin T1/2 |
13.02; 12.94 | — |
| SECONDARY Metformin AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf]) |
0.967; 0.963 | — |
| SECONDARY Metformin Tmax |
4.38; 4.84; 5.00 | — |
| SECONDARY Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs) |
3; 3; 4; 0; 0; 0 | — |
| SECONDARY Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Healthy male and female subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
- Body Mass Index (BMI) of 18 to 32 kg/m², inclusive
- Ages 18 to 55, 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 HIV, HBV or 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
Data sourced from ClinicalTrials.gov (NCT01192152). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.