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Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01068717
First received: February 12, 2010
Last updated: June 4, 2014
Last verified: June 2014

February 12, 2010
June 4, 2014
March 2010
March 2010   (final data collection date for primary outcome measure)
  • Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
  • Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
  • Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ] [ Designated as safety issue: Yes ]
  • Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
  • AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
  • AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
  • AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
  • Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States [ Time Frame: Days 1, 2, and 3 of Periods 1, 2, 3, and 4 ] [ Designated as safety issue: No ]
Evidence of bioequivalence between FDC of saxagliptin and metformin with co-administrated saxagliptin and metformin (Glucophage Marketed in Canada by Sanofi-Aventis) in the fasted and fed state in healthy subjects [ Time Frame: Within the first 24 hours of dosing ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01068717 on ClinicalTrials.gov Archive Site
  • Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation [ Time Frame: Continuously over Days 1 to 3 of treatment Periods 1, 2, 3, and 4 ] [ Designated as safety issue: Yes ]
    An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
  • Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results [ Time Frame: At screening visit, at Day -1 of Periods 1 through 4, and at discharge ] [ Designated as safety issue: Yes ]
    Clinically significant was determined by the investigator. Hematology tests included hemoglobin, hematocrit, red blood cell count, total leukocyte count (including differential), and platelet count. Serum chemistry tests included aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, lactate dehydrogenase, creatinine, blood urea nitrogen, uric acid, fasting glucose, total protein, albumin, sodium, potassium, chloride, calcium, phosphorus, and creatine kinase. Urinalysis included protein, glucose, blood, leukocyte esterase, specific gravity, and pH.
  • Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results [ Time Frame: At screening visit, Day -1 of Period 1, and at study discharge ] [ Designated as safety issue: Yes ]
    Clinically significant was determined by the investigator. ECGs were recorded after participants had been supine for at least 5 minutes.
  • Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate [ Time Frame: At screening visit, prior to dosing on Day 1 of Periods 1 through 4, and at study discharge. ] [ Designated as safety issue: Yes ]
    Clinically significant was determined by the investigator. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes.
  • To assess the pharmacokinetics of the active metabolite of saxagliptin, BMS-510849, when saxagliptin is co-administered with a metformin (Glucophage) tablet and in a FDC tablet with metformin under fasted and under fed condition in healthy subjects [ Time Frame: 14 time points up to 24 hours after dosing ] [ Designated as safety issue: Yes ]
  • To assess the safety and tolerability of 2.5 mg saxagliptin when co-administered with a 500 mg metformin IR tablet and in a FDC tablet with metformin IR under fasted and under fed condition in healthy subjects [ Time Frame: 14 time points up to 24 hours after dosing ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants
Bioequivalence Study of the Fixed Dose Combination of 2.5 mg Saxagliptin and 500 mg Metformin Tablet Relative to a 2.5 mg Saxagliptin (Onglyza) Tablet and a 500 mg Metformin (Glucophage Marketed in Canada by Sanofi-Aventis) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed States

To demonstrate the bioequivalence of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet to that of 2.5-mg saxagliptin (Onglyza) and 500-mg metformin (Glucophage, marketed in Canada by Sanofi-Aventis) tablets coadministered to healthy participants in the fasted and fed states.

Not Provided
Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Type 2 Diabetes Mellitus
  • Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)
    Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week
    Other Names:
    • Onglyza™
    • Glucophage™
  • Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state)
    Tablets, oral, 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC), once daily, 1 week
  • Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state)
    Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week
    Other Names:
    • Onglyza™
    • Glucophage™
  • Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state)
    Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin FDC, once daily, 1 week
  • Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)
    Single oral doses of saxagliptin, 2.5 mg, and metformin, 500 mg, administered together as tablets in the fasted state
    Intervention: Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)
  • Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fasted state)
    Single oral dose of a 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) tablet administered in the fasted state
    Intervention: Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state)
  • Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state)
    Single oral doses of saxagliptin, 2.5 mg, and metformin, 500 mg, administered together as tablets in the fed state
    Intervention: Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state)
  • Saxagliptin, 2.5 mg/Metformin, 500 mg FDC (fed state)
    Single oral dose of saxagliptin, 2.5 mg/metformin, 500 mg, FDC tablet administered in the fed state
    Intervention: Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
27
March 2010
March 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Men and women, aged 18 to 55 years, inclusive
  • Healthy participants as determined by a lack of clinically significant deviation from normal in medical history, physical examination, electrocardiograms, and clinical laboratory determinations
  • Body Mass Index of 18 to 32 kg/m^2, inclusive

Exclusion Criteria:

  • Any significant acute or chronic medical illness
  • Current or recent (within 3 months) gastrointestinal disease
  • Any major surgery within 4 weeks of study drug administration
  • History of allergy to DPP-4 inhibitors or related compounds
  • History of allergy or intolerance to metformin or other similar acting agents
  • Previous exposure to saxagliptin
  • Exposure to metformin within 3 months pervious to study drug administration
  • Estimated creatinine clearance of <80 mL/min using the Cockcroft Gault formula
Both
18 Years to 55 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01068717
CV181-118
No
AstraZeneca
AstraZeneca
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
AstraZeneca
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP