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

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus(T2DM)
• Intervention / Treatment: Drug: Saxagliptin 5 mg; Drug: Metformin XR 500 mg; Drug: Komboglyze XR 5/500 mg; Drug: Mertformin XR 2 x 500 mg; Drug: Komboglyze XR 5/1000 mg

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

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	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
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	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
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	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
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	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) for 5-hydroxy saxagliptin		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
Area under plasma concentration time curve (AUC) for 5-hydroxy saxagliptin		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
Safety and tolerability assessment based on medical review of AE reports:physical examination, ECG, heart rate, blood pressure, lab test	Assessment for 5 mg saxagliptin co-administered with up to 1000 mg metformin XR given either separately, or as a single FDC tablet.	Study duration for individual subject (up to 34 days) when the safety data are collected

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: 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

Publications and helpful links

Helpful Links

• D1681C00001.pdf

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (ACTUAL): April 1, 2013
• Study Completion (ACTUAL): April 1, 2013

Study Registration Dates

• First Submitted: December 12, 2012
• First Submitted That Met QC Criteria: December 19, 2012
• First Posted (ESTIMATE): December 24, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 13, 2013
• Last Update Submitted That Met QC Criteria: December 12, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Type 2 diabetes, Saxagliptin, Metformin,Fixed dose combination tablet, Bioequivalence, pharmacokinetic, safety, tolerability
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Saxagliptin
• Other Study ID Numbers: D1681C00001