Study in Healthy Subjects to Measure Amount of Drug in Blood After Dosing With Different Saxagliptin / Metformin Produc

Bioequivalence Study of the Fixed-dose Combination of Saxagliptin/Metformin XR Tablets Relative to Saxagliptin (Onglyza� ) Tablets and Australia-sourced Diabex XR Tablets Coadministered to Healthy Subjects in the Fed State During Steady-state Administration

Study in healthy subjects to measure amount of drug in blood after dosing with different saxagliptin / metformin products.

Study Overview

• Status: Completed
• Conditions: Bioequivalence, Log-transformed AUCss and Cmax,ss Values for Saxagliptin and Metformin
• Intervention / Treatment: Drug: Onglyza (saxagliptin); Drug: Diabex; Drug: Diabex; Drug: 5-mg saxagliptin/1000 mg metformin; Drug: 5-mg saxagliptin/500 mg metformin

Detailed Description

Bioequivalence Study of the Fixed-dose Combination of Saxagliptin/Metformin XR Tablets Relative to Saxagliptin (Onglyza� ) Tablets and Australia-sourced Diabex XR Tablets Coadministered to Healthy Subjects in the Fed State During Steady-state Administration

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Provision of signed and dated informed consent prior to any study specific procedures
• Males or females aged 18 to 55 years (inclusive) and with a weight of at least 50 kg and a body mass index (BMI) between 18 and 35 kg/m2, inclusive
• Females must have a negative urine pregnancy test at screening and negative serum pregnancy test on admission to the unit, must not be lactating, and must be using an acceptable method of contraception for at least 1 month before dosing
• Female volunteers of childbearing potential (including perimenopausal women who have had a menstrual period within 1 year) must be using appropriate birth control (defined as a method which results in a low failure rate, ie, less than 1% per year
• Oral contraceptive and hormone replacement medications are allowed in this study if used together with a barrier contraceptive method.

Exclusion Criteria:

• History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate
• History or presence of gastrointestinal, hepatic, renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs (except for cholecystectomy)
• Glomerular filtration rate of less than 60 mL/min (to be estimated at screening only)
• Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product (IP)
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, as judged by the Investigator (eg, seasonal allergies) or history of hypersensitivity to drugs with a similar chemical structure or class to saxagliptin or metformin

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; 5-mg Onglyza (saxagliptin) tablet +1000-mg Diabex extended release tablet	Drug: Onglyza (saxagliptin); Oral tablets, 5 mg , single dose; Drug: Diabex; Extended release oral tablets, 1000 mg, single dose; Drug: Diabex; Extended release oral tablets, 500 mg, single dose
EXPERIMENTAL: B; 5-mg saxagliptin/1000 mg metformin extended release fixed dose combination tablet	Drug: Onglyza (saxagliptin); Oral tablets, 5 mg , single dose; Drug: 5-mg saxagliptin/1000 mg metformin; Extended release fixed dose combination tablet, single dose
EXPERIMENTAL: C; 5-mg Onglyza (saxagliptin) tablet + 500-mg Diabex extended release tablet	Drug: Diabex; Extended release oral tablets, 1000 mg, single dose; Drug: Diabex; Extended release oral tablets, 500 mg, single dose
EXPERIMENTAL: D; 5-mg saxagliptin/500 mg metformin extended release fixed dose combination tablet	Drug: 5-mg saxagliptin/500 mg metformin; Extended release fixed dose combination tablet, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PK Saxagliptin: Observed maximum concentration at steady state (Cmax,ss), time of maximum concentration (tmax,ss) at steady state, and area under the concentration-time curve from zero to the end of the dosing interval at steady state (AUCss)	At day 5 to day 6 at visit 2 or 3
PK : Metformin Observed maximum concentration at steady state (Cmax,ss), time of maximum concentration (tmax,ss) at steady state, and area under the concentration-time curve from zero to the end of the dosing interval at steady state (AUCss)	At day 5 to day 6 at visit 2 or 3

Secondary Outcome Measures

Outcome Measure	Time Frame
PK : Saxagliptin 5-hydroxy Observed maximum concentration at steady state (Cmax,ss), time of maximum concentration (tmax,ss) at steady state, and area under the concentration-time curve from zero to the end of the dosing interval at steady state (AUCss)	At day 5 to day 6 at visit 2 or 3
Safety will be assessed by the incidence, severity, and relatedness of adverse events.	From day -1 visit 2 until performed follow up ( Approximately 30 days)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Chair: Miriana Kujacic, MD, AstraZeneca Mölndal, Sweden; Principal Investigator: Phil Leese, MD, Quintiles, Inc. Overland Park US; Study Director: Peter Öhman, MD, Astrazeneca, Wilmington, US

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: September 26, 2011
• First Submitted That Met QC Criteria: September 26, 2011
• First Posted (ESTIMATE): September 28, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 8, 2012
• Last Update Submitted That Met QC Criteria: February 7, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Phase 1, Healthy male volunteers, pharmacokinetics, saxagliptin/ metformin , Diabex
• Additional Relevant MeSH Terms: 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: D1681C00004