BE Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin HCl XR Tablet Relative to a 5 mg Saxagliptin (Onglyza™) Tablet and a 500 mg Metformin HCl XR (Glifage® XR Marketed in Brazil by Merck S.A.) Tablet Co-Administered to Healthy Subjects in the Fasted and Fed States

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01305551
First received: February 25, 2011
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to demonstrate the bioequivalence (BE) of Saxagliptin and Metformin from a 5 mg Saxagliptin/500 mg Metformin extended release (XR) fixed dose combination (FDC) tablet relative to 5 mg Onglyza™ and 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) tablets administered together in both the fasted and fed states.


Condition Intervention Phase
Type 2 Diabetes
Drug: Saxagliptin
Drug: Metformin XR
Drug: Saxagliptin/Metformin XR FDC
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin Hydrochloride (HCl) XR Tablet Relative to a 5 mg Saxagliptin (Onglyza™) Tablet and a 500 mg Metformin HCl XR (Glifage® XR Marketed in Brazil by Merck S.A.) 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:
  • Evidence of BE on single-dose pharmacokinetic parameters maximum observed concentration (Cmax) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: 48 hours after dosing ] [ Designated as safety issue: No ]
  • Evidence of BE on single-dose pharmacokinetic parameters time of maximum observed concentration (Tmax) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: 48 hours after dosing ] [ Designated as safety issue: No ]
  • Evidence of BE on single-dose pharmacokinetic parameters (AUC(0-T) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: 48 hours after dosing ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from time zero to the time of the last quantifiable concentration (AUC(0-T))

  • Evidence of BE on single-dose pharmacokinetic parameters area under the concentration-time curve from time zero extrapolated to infinite time (AUC(INF)) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: 48 hours after dosing ] [ Designated as safety issue: No ]
  • Evidence of BE on single-dose pharmacokinetic parameters half-life (T-HALF) derived from Saxagliptin, 5-Hydroxy Saxagliptin and Metformin plasma concentration versus time data. [ Time Frame: 48 hours after dosing ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 3 days after dosing ] [ Designated as safety issue: No ]
  • Active metabolite of Saxagliptin, 5-Hydroxy Saxagliptin, from 5 mg Saxagliptin/500 mg Metformin XR FDC tablet & from 5 mg Onglyza administered together with 500 mg Glifage® XR in single-dose fed & fasted state pharmacokinetics in healthy subjects [ Time Frame: 3 days after dosing ] [ Designated as safety issue: No ]
    Amount of the active metabolite of Saxagliptin, 5-Hydroxy Saxagliptin (BMS-510849), from the 5 mg Saxagliptin/500 mg Metformin XR FDC tablet and from 5 mg Onglyza™ administered together with 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) in single-dose fed and fasted state pharmacokinetics in healthy subjects


Enrollment: 0
Study Start Date: March 2011
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A-Saxagliptin+Metformin XR
5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fasted state.
Drug: Saxagliptin
Tablet, Oral, 5 mg, once on Day 1 only
Other Name: Onglyza
Drug: Metformin XR
Tablet, Oral, 500 mg, once on Day 1 only
Other Name: Glifage XR
Experimental: Treatment B-Saxagliptin/Metformin XR FDC
5mg Saxagliptin / 500 mg Metformin XR FDC tablet, once on Day 1 only, administered in the fasted state.
Drug: Saxagliptin/Metformin XR FDC
Tablet, Oral, 5/500 mg, once on Day 1 only
Other Name: Onglyza/Glucophage
Experimental: Treatment C-Saxagliptin+Metformin XR
5mg Saxagliptin + 500 mg Metformin XR Tablets, once on Day 1 only, administered together in the fed state.
Drug: Saxagliptin
Tablet, Oral, 5 mg, once on Day 1 only
Other Name: Onglyza
Drug: Metformin XR
Tablet, Oral, 500 mg, once on Day 1 only
Other Name: Glifage XR
Experimental: Treatment D-Saxagliptin/Metformin XR FDC
5mg Saxagliptin / 500 mg Metformin XR FDC tablet, once on Day 1 only, administered in the fed state.
Drug: Saxagliptin/Metformin XR FDC
Tablet, Oral, 5/500 mg, once on Day 1 only
Other Name: Onglyza/Glucophage

Detailed Description:

Primary purpose: To demonstrate the bioequivalence of Saxagliptin and Metformin from a 5 mg Saxagliptin/500 mg Metformin XR FDC tablet relative to 5 mg Onglyza™ and 500 mg Glifage® XR (marketed in Brazil by Merck S.A.) tablets administered together in both the fasted and fed states.

  Eligibility

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

Inclusion Criteria:

  • Healthy men and women
  • Women of childbearing potential (WOCBP) who are using acceptable method of contraception
  • Women who are not nursing

Exclusion Criteria:

  • History of Gastrointestinal (GI) disease
  • Any GI surgery that could impact study drug absorption
  • History of allergy to drug class or related compounds
  • History of allergy to metformin or other similar acting agents.
  • History of any significant drug allergy.
  • Estimated creatinine clearance (ClCr) < 80 mL/min using 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: NCT01305551

Locations
Brazil
Local Institution
Campinas, Sao Paulo, Brazil, 13073
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01305551     History of Changes
Other Study ID Numbers: CV181-146
Study First Received: February 25, 2011
Last Updated: June 4, 2014
Health Authority: Brazil: Ethics Committee
Brazil: National Health Surveillance Agency

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
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 20, 2014