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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01068717
• Other study ID #: CV181-118
• Status: Completed
• Phase: Phase 1
• First received: February 12, 2010
• Last updated: April 22, 2015
• Start date: March 2010
• Est. completion date: March 2010

Study information

• Verified date: April 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Saxagliptin, 2.5 mg + Metformin, 500 mg (fasted state)
Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week
• 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)
Tablets, oral, 2.5-mg saxagliptin and 500-mg metformin, once daily, 1 week
• 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

Locations

Country	Name	City	State
United States	Ppd Development, Lp	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	Yes
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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.	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form