Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN)

NCT01192139 | Completed Phase 1 Results

• 1 other identifier: CV181-111
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to demonstrate bioequivalence (BE) of a 5 mg saxagliptin/500 mg metformin extended release (XR) fixed-dose combination (FDC) tablet (manufactured in Mt Vernon, Indiana \[IN\]) to coadministered 5 mg saxagliptin and 500 mg metformin XR tablet (manufactured in Evansville, IN) in fed healthy subjects.

Conditions

Diabetes Mellitus

Outcome Measures

Primary Outcomes (4)

• Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])

  Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t \[calculated using the linear trapezoidal rule\] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

• Saxagliptin Observed Maximum Plasma Concentration (Cmax)

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

• Metformin AUC(0-inf)

  Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t \[calculated using the linear trapezoidal rule\] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

• Metformin Cmax

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

Secondary Outcomes (16)

• Saxagliptin Terminal Half-life (T1/2)

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

• Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

• Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax)

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

• Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

• Active Metabolite BMS-510849 AUC(0-inf)

  Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

Study Arms (3)

5 mg saxagliptin + a single 500 mg metformin XR tablet

EXPERIMENTAL

Drug: saxagliptin; Drug: metformin XR

FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fed)

EXPERIMENTAL

under fed state

Drug: saxagliptin + metformin XR (FDC tablet)

FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fasting)

EXPERIMENTAL

under fasted state

Drug: saxagliptin + metformin XR (FDC tablet)

Interventions

saxagliptin DRUG

Tablets, Oral, 5 mg, once daily, Single dose

Also known as: Onglyza

5 mg saxagliptin + a single 500 mg metformin XR tablet

metformin XR DRUG

Tablets, Oral, 500 mg. once daily, Single dose

Also known as: Glucophage XR

5 mg saxagliptin + a single 500 mg metformin XR tablet

saxagliptin + metformin XR (FDC tablet) DRUG

Tablet, Oral, (saxagliptin 5 mg)(metformin XR 500 mg), once daily, Single dose

FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fasting); FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fed)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiogram (ECG), and clinical laboratory determinations
• Body Mass Index (BMI) of 18 to 32 kg/m2, inclusive
• Ages 18 to 45, inclusive

You may not qualify if:

• 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 human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Ppd Development, Lp

Austin, Texas, 78744, United States

Location

Related Publications (1)

• Boulton DW, Smith CH, Li L, Huang J, Tang A, LaCreta FP. Bioequivalence of saxagliptin/metformin extended-release (XR) fixed-dose combination tablets and single-component saxagliptin and metformin XR tablets in healthy adult subjects. Clin Drug Investig. 2011;31(9):619-30. doi: 10.2165/11590290-000000000-00000.

  PMID: 21819160 DERIVED

Related Links

• Investigator Inquiry form

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

saxagliptin; Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Boaz Hirschberg
• Organization: AstraZeneca Pharmaceuticals

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2010
• First Posted: August 31, 2010
• Study Start: November 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 21, 2015
• Results First Posted: May 17, 2011

Record last verified: 2015-05

Locations

US (1)