A Bioequivalence Study of the Fixed Dose Combinations of Saxagliptin/Metformin XR Relative to Co-Administration (SAXA)

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01755494
First received: December 12, 2012
Last updated: December 12, 2013
Last verified: December 2013
  Purpose

The primary objective of this study is to assess the pharmacokinetic parameters of saxagliptin and metformin in healthy male Chinese subjects.


Condition Intervention Phase
Type 2 Diabetes Mellitus(T2DM)
Drug: Saxagliptin 5 mg
Drug: Metformin XR 500 mg
Drug: Mertformin XR 2 x 500 mg
Drug: Komboglyze XR 5/500 mg
Drug: Komboglyze XR 5/1000 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Single-centre, Randomized, Open-label, Two-period, Cross-over, Bioequivalence Study of the Fixed Dose Combinations of Saxagliptin/Metformin XR Relative to Co-Administration of the Individual Components in Two Cohorts of Healthy Chinese Subjects Under Fed Conditions

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Maximum plasma concentration (Cmax) for saxagliptin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets [ Time Frame: Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Maximum plasma concentration (Cmax) for metformin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets [ Time Frame: Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Area under plasma concentration time curve (AUC) for saxagliptin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets [ Time Frame: Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Area under plasma concentration time curve (AUC) for metformin during treatment with fixed dose combination tablet of metformin plus saxagliptin compared with individual metformin XR and saxaglitpin tablets [ Time Frame: Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Maximum plasma concentration (Cmax) for 5-hydroxy saxagliptin [ Time Frame: Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Area under plasma concentration time curve (AUC) for 5-hydroxy saxagliptin [ Time Frame: Plasma samples at 0, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 hours post-dose ] [ Designated as safety issue: No ]
  • Safety and tolerability assessment based on medical review of AE reports:physical examination, ECG, heart rate, blood pressure, lab test [ Time Frame: Study duration for individual subject (up to 34 days) when the safety data are collected ] [ Designated as safety issue: Yes ]
    Assessment for 5 mg saxagliptin co-administered with up to 1000 mg metformin XR given either separately, or as a single FDC tablet.


Enrollment: 64
Study Start Date: February 2013
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lower dose
co-administration of a single oral dose of a 5 mg saxagliptin tablet and a 500 mg metformin XR (Glucophage XR®) tablet vs. single FDC tablet consisting of 5 mg saxagliptin and 500 mg metformin XR (Kombiglyze XR)
Drug: Saxagliptin 5 mg
Saxagliptin oral tablet 5mg, single dose
Drug: Metformin XR 500 mg
Metformin XR oral tablet 500 mg, single dose
Drug: Komboglyze XR 5/500 mg
oral FDC tablet (saxagliptin 5 mg and metformin 500 mg), single dose
Experimental: Higher dose
co-administration of a single oral dose of a 5 mg saxagliptin tablet and two (2) 500 mg metformin XR (Glucophage XR®) tablets vs. Single FDC tablet consisting of 5 mg saxagliptin and 1000 mg metformin XR (Kombiglyze XR)
Drug: Saxagliptin 5 mg
Saxagliptin oral tablet 5mg, single dose
Drug: Mertformin XR 2 x 500 mg
Metformin XR oral tablet 2 x 500 mg, single dose
Drug: Komboglyze XR 5/1000 mg
oral FDC tablet (saxagliptin 5 mg and metformin 1000 mg), single dose

Detailed Description:

A Single-centre, Randomized, Open-label, Two-period, Cross-over, Bioequivalence Study of the Fixed Dose Combinations of Saxagliptin/Metformin XR Relative to Co-Administration of the Individual Components in two cohorts of Healthy Chinese Subjects under Fed Conditions

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Chinese ethnicity which is defined as having both parents and 4 grandparents who are Chinese
  • Healthy male subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations
  • Men, ages 18 to 40 years, inclusive. The age difference among the subjects is within 10 years
  • Weigh at least 50 kg and have a body mass index (BMI) between 19 and 24 kg/m2
  • Sexually active fertile men must use effective birth control throughout the study and for up to 90 days after the last dose of investigational product if their partners are women of child bearing potential

Exclusion Criteria:

  • Any significant acute or chronic medical illness
  • Current or recent gastrointestinal disease
  • Subjects that have lymphocytopenia or thrombocytopenia
  • History of autoimmune skin disorder
  • Estimatedcreatinine clearance of less than 80 mL/min
  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: NCT01755494

Locations
China
Research Site
Beijing, China
Sponsors and Collaborators
AstraZeneca
Bristol-Myers Squibb
Investigators
Study Director: Boaz Hirshberg Room No.: C3C-718, 1800 Concord Pike, PO Box 15437, Wilmington DE 19850-5437, USA
Principal Investigator: Haiyan Li Peking University Third Hospital (PU3), 49 North Garden Road, Haidian District, Beijing 100191, PR. China
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01755494     History of Changes
Other Study ID Numbers: D1681C00001
Study First Received: December 12, 2012
Last Updated: December 12, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by AstraZeneca:
Type 2 diabetes, Saxagliptin, Metformin,Fixed dose combination tablet, Bioequivalence, pharmacokinetic, safety, tolerability

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
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 21, 2014