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
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: 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 July 24, 2014