To Compare the Similarity of a Combination Dapagliflozin/Metformin Tablet With the Two Drugs Administered Separately

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01535677
First received: January 13, 2012
Last updated: July 15, 2013
Last verified: July 2013
  Purpose

This is an open-label, randomised study to compare the similarity of a combination Dapagliflozin/Metformin tablet with the two drugs administered separately under fasting and fed conditions in healthy volunteers.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Dapagliflozin + Glucophage tablet fasted
Drug: Dapagliflozin/metformin IR FDC tablet fasted
Drug: Dapagliflozin + Glucophage tablet fed
Drug: Dapagliflozin/metformin IR FDC tablet fed
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 Bioequivalence Study of the Fixed Dose Combination Dapagliflozin/Metformin Tablet (5 mg/850 mg) Relative to a 5 mg Dapagliflozin Tablet and an 850 mg Metformin (Glucophage® Marketed in Canada by Sanofi-Aventis) 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:
  • Area under the curve over the time (AUC) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed

  • AUC from time zero to the time of last quantifiable analyte concentration (AUC(0-t)) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed

  • Maximum concentration (Cmax) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed


Secondary Outcome Measures:
  • Time to reach maximum analyte concentration (tmax) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: No ]
    No statistical analysis will be performed

  • Terminal rate constant (λz) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: No ]
    No statistical analysis will be performed

  • Time of last quantifiable analyte concentration (tlast) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: No ]
    No statistical analysis will be performed

  • Terminal half-life (t1/2) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: No ]
    No statistical analysis will be performed

  • Observed maximum analyte concentration (Cmax) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: No ]
    No statistical analysis will be performed

  • Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: No ]
    No statistical analysis will be performed

  • Area under the plasma concentration-curve from time zero to the time of last quantifiable analyte concentration (AUC(0 t)) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: No ]
    No statistical analysis will be performed

  • Elimination terminal half-life (t1/2) [ Time Frame: pre-dose, 0.25 min, 0.5 min, 1h, 1.5h, 2 h, 3h , 4 h, 5 h , 6 h, 8 h, 10 h, 12 h, 16 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h and 72 h post-dose ] [ Designated as safety issue: No ]
    No statistical analysis will be performed

  • Safety profile description in term of Adverse Events [ Time Frame: from first dose in treatment period 1 up to 10 days after final dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed

  • Safety profile description in term of Blood Pressure [ Time Frame: at screening, once daily during the residential period (5 days each) and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed

  • Safety profile description in term of Physical Examination [ Time Frame: at screening, Day -1 and Day 4 at Visits 2 to 5 and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed

  • Safety profile description in term of Electrocardiogram ECG [ Time Frame: at screening and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed

  • Safety profile description in term of Heart Rate [ Time Frame: at screening, once daily during the residential period (5 days each) and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed

  • Safety profile description in term of Safety Labs [ Time Frame: at screening, on Day -1 and Day 4 (72 hours post-dose) at Visits 2 to 5 and up to 10 days after final dose ] [ Designated as safety issue: Yes ]
    No statistical analysis will be performed


Enrollment: 40
Study Start Date: April 2013
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
5 mg dapagliflozin and 850 mg Glucophage in fasted state
Drug: Dapagliflozin + Glucophage tablet fasted
Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fasted state
Experimental: 2
dapagliflozin/metformin (5 mg/850 mg) immediate release (IR) FDC in fasted
Drug: Dapagliflozin/metformin IR FDC tablet fasted
single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fasted state
Experimental: 3
5 mg dapagliflozin and 850 mg Glucophage in fed state
Drug: Dapagliflozin + Glucophage tablet fed
Single oral doses of 5 mg dapagliflozin and 850 mg Glucophage® tablets administered together in the fed state
Experimental: 4
dapagliflozin/metformin (5 mg/850 mg) IR FDC in fed state
Drug: Dapagliflozin/metformin IR FDC tablet fed
single oral dose of dapagliflozin/metformin (5 mg/850 mg) IR FDC tablet in the fed state

Detailed Description:

A Bioequivalence Study of the Fixed Dose Combination Dapagliflozin/Metformin Tablet (5.0 mg/850 mg) Relative to a 5.0 mg Dapagliflozin Tablet and an 850 mg Metformin (Glucophage® Marketed in Canada by Sanofi-Aventis) Tablet Co-Administered to Healthy Subjects in 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 volunteers aged 18 to 55 years inclusive with suitable veins for cannulation or repeated vein puncture
  • Male subjects should be willing to use barrier contraception ie, condoms and spermicide, from the day of dosing until at least 3 months after dosing with the investigational product
  • Non-pregnant, non-lactating female subjects who if pre-menopausal are using adequate birth control eg, oral, injectable, transdermal or implanted hormonal contraceptives, vaginal contraceptive ring, intrauterine device (IUD)/intrauterine systems
  • Have a body mass index (BMI) between 18.5 and 30.0 kg/m2 inclusive (ie, within 15% of normal range) and weigh at least 50 kg and no more than 100 kg.

Exclusion Criteria:

  • History or presence of gastrointestinal, hepatic or renal disease or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with individual safety evaluation Current smokers who smoke more than 5 cigarettes per day (or equivalent use of tobacco products) or cannot give up smoking during the study
  • Excessive intake of caffeine containing drinks eg, coffee, tea, caffeine containing energy drinks and cola (more than 5 cups of coffee or equivalent per day)
  • Plasma donation within one month of screening or any blood donation/blood loss >500 mL during the 3 months prior to screening
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01535677

Locations
United Kingdom
London, United Kingdom
Sponsors and Collaborators
AstraZeneca
Bristol-Myers Squibb
Investigators
Study Director: Eva Johnsson, MD AstraZeneca Research and Development SE-431 83 Mölndal Sweden
Principal Investigator: Saeed Kahn, MBBS Quintiles Drug Research Unit at Guy's Hospital, 6 Newcomen St, London SE1 1YR
Study Chair: Mirjana Kujacic, PHD AstraZeneca Research and DevelopmentSE-431 83 Mölndal Sweden
  More Information

No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01535677     History of Changes
Other Study ID Numbers: D1691C00007
Study First Received: January 13, 2012
Last Updated: July 15, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Phase 1
healthy volunteers
cross-over study
Bioavailability
Bioequivalence
Cmax
tmax
AUC
AUC(0-t)
λz
tlast

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014