Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin/1000 mg Metformin XR (Manufactured in Mt Vernon, IN) Relative to 5 mg of Onglyza and 2 × 500 mg Glucophage XR

NCT01192152 | Completed Phase 1 Results

• 1 other identifier: CV181-112
• 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/1000 mg metformin extended release (XR) fixed-dose combination (FDC) tablet (manufactured in Mt Vernon, Indiana) relative to a coadministered 5 mg Onglyza tablet (saxagliptin, manufactured in Mt Vernon, Indiana) and two 500 mg Glucophage XR tablets (metformin XR, manufactured in Evansville, Indiana) in the fed state in 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])

  Periods 1 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing.

• Saxagliptin Observed Maximum Plasma Concentration (Cmax)

  Periods 1 & 2: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 & 48 hrs post-dosing. Period 3: predosing on Days 2 & 3; predosing, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hrs postdosing on Day 4

• Metformin AUC(0-inf)

  Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.

• Metformin Cmax

  Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4.

Secondary Outcomes (28)

• 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 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing.

• Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau])

  Period 3: pre-dosing on Days 2 and 3; pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours post-dosing on Day 4.

• Saxagliptin Trough (Predose) Plasma Concentration (Cmin)

  Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.

• Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg)

  Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.

• Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %)

  Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.

Study Arms (3)

5 mg saxagliptin + 2 Glucophage XR 500 mg tablet

EXPERIMENTAL

Drug: saxagliptin; Drug: Glucophage XR

FDC tablet (5 mg saxa + 1000 mg metformin XR) (single dose)

EXPERIMENTAL

under fed state, single dose

Drug: saxagliptin + metformin XR (FDC tablet)

FDC tablet (5 mg saxa + 1000 mg metformin XR) (4 days)

EXPERIMENTAL

under fed state, 4 days

Drug: saxagliptin + metformin XR (FDC tablet)

Interventions

saxagliptin DRUG

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

Also known as: Onglyza

5 mg saxagliptin + 2 Glucophage XR 500 mg tablet

Glucophage XR DRUG

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

5 mg saxagliptin + 2 Glucophage XR 500 mg tablet

saxagliptin + metformin XR (FDC tablet) DRUG

Tablet, Oral, (saxagliptin 5 mg)(metformin XR 1000 mg), once daily, 4 days

Also known as: Onglyza

FDC tablet (5 mg saxa + 1000 mg metformin XR) (4 days); FDC tablet (5 mg saxa + 1000 mg metformin XR) (single dose)

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, ECGs, and clinical laboratory determinations
• Body Mass Index (BMI) of 18 to 32 kg/m², inclusive
• Ages 18 to 55, 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 HIV, HBV or 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 12, 2015
• Results First Posted: May 17, 2011

Record last verified: 2015-03

Locations

US (1)