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
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)
Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fasted state)
Drug: Saxagliptin, 2.5 mg + Metformin, 500 mg (fed state)
Drug: Saxagliptin, 2.5 mg /Metformin, 500 mg FDC (fed state)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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.


Enrollment: 27
Study Start Date: March 2010
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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™
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
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
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
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™
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
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

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01068717

Locations
United States, Texas
Ppd Development, Lp
Austin, Texas, United States, 78744
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01068717     History of Changes
Other Study ID Numbers: CV181-118
Study First Received: February 12, 2010
Results First Received: August 10, 2011
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Saxagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014