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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: 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)

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD Development, LP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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™
Other: 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
Other: 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™
Other: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States	Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States	Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States	Days 1, 2, and 3 of Periods 1, 2, 3, and 4
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	Days 1, 2, and 3 of Periods 1, 2, 3, and 4
AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States	Days 1, 2, and 3 of Periods 1, 2, 3, and 4
AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States	Days 1, 2, and 3 of Periods 1, 2, 3, and 4
AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States	Days 1, 2, and 3 of Periods 1, 2, 3, and 4
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	Days 1, 2, and 3 of Periods 1, 2, 3, and 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation	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.	Continuously over Days 1 to 3 of treatment Periods 1, 2, 3, and 4
Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results	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.	At screening visit, at Day -1 of Periods 1 through 4, and at discharge
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Clinically significant was determined by the investigator. ECGs were recorded after participants had been supine for at least 5 minutes.	At screening visit, Day -1 of Period 1, and at study discharge
Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate	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.	At screening visit, prior to dosing on Day 1 of Periods 1 through 4, and at study discharge.

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: February 12, 2010
• First Submitted That Met QC Criteria: February 12, 2010
• First Posted (Estimate): February 15, 2010

Study Record Updates

• Last Update Posted (Estimate): May 12, 2015
• Last Update Submitted That Met QC Criteria: April 22, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Saxagliptin
• Other Study ID Numbers: CV181-118