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Bioequivalence Study Coadministered to Healthy Subjects in the Fasted State

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02223065
Recruitment Status : Completed
First Posted : August 22, 2014
Results First Posted : April 27, 2016
Last Update Posted : April 27, 2016
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
The purpose of this study is to demonstrate bioequivalence of coadministered drugs on healthy subjects.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Saxagliptin Drug: Dapagliflozin Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: A Bioequivalence Study of Fixed-dose Combination Tablet of 5 Milligrams Saxagliptin/10 Milligrams Dapagliflozin Relative to Their Respective Individual Components Coadministered to Healthy Subjects in the Fasted State
Study Start Date : September 2014
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment A
Single oral dose of saxagliptin tablet coadministered with dapagliflozin tablet
Drug: Saxagliptin
Other Name: Onglyza

Drug: Dapagliflozin
Other Names:
  • Farxiga in the United States
  • Forxiga in other countries

Experimental: Treatment B
Single oral dose of FDC (fixed-dose combination) tablet
Drug: Saxagliptin
Other Name: Onglyza

Drug: Dapagliflozin
Other Names:
  • Farxiga in the United States
  • Forxiga in other countries




Primary Outcome Measures :
  1. Saxagliptin Maximum Observed Concentrations (Cmax) [ Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2) ]
    5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

  2. Dapagliflozin Maximum Observed Concentrations (Cmax) [ Time Frame: Day 1 to 3 (Period 1) and Day 8 to 10 (Period 2) ]
    5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

  3. Saxagliptin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T]) [ Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2) ]
    5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

  4. Dapagliflozin AUC From Time 0 to Time of the Last Quantifiable Concentration (AUC[0-T]) [ Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2) ]
    5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

  5. Saxagliptin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) [ Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2) ]
    5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state

  6. Dapagliflozin AUC From Time 0 Extrapolated to Infinite Time (AUC[0-inf]) [ Time Frame: Day 1-3 (Period 1) and Day 8-10 (Period 2) ]
    5-mg saxagliptin/10-mg dapagliflozin as a Fixed-dose Combination (FDC) and as Individual Tablets together in the fasted state



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Signed Informed Consent Form

    • Signed written informed consent must be obtained from the subjects in accordance with requirements of the study center's IRB or IEC before the initiation of any protocol-required procedures.
  2. Target Population

    • Healthy subjects as determined by no clinically significant deviation from normal in medical history, psychiatric history, physical examination findings, vital sign measurements, 12-lead ECG measurements, physical measurements, and clinical laboratory test results.
  3. Age and Reproductive Status

    • Males and females, ages 19 to 55 years, inclusive. To extent possible, the distribution of men and women between the sequences will be balanced
    • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug.
    • Women must not be breastfeeding. d) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs saxagliptin and dapagliflozin plus 5 half lives of study drug dapagliflozin (the longer half life between the 2 drugs; 3 days) for a total of 3 days following treatment completion.

      e) Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drugs saxagliptin and dapagliflozin plus 5 half lives of dapagliflozin (the longer half life between the 2 drugs; 3 days) for a total of 3 days following treatment completion.

      f) Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described in this section

    Exclusion Criteria:

    • Any significant acute or chronic medical illness.
    • Current or recent (within 3 months of study drug administration) gastrointestinal disease that could impact upon the absorption of study drug
    • Any other sound medical, psychiatric, and/or social reason as determined by the investigator
    • Any major surgery within 4 weeks of study drug administration.
    • Any prior GI surgery including cholecystectomy (remote history of appendectomy will not be exclusionary).
    • Current, recent (within 3 months of study drug administration), or remote history of pancreatitis.
    • Donation of blood or plasma to a blood bank or in a clinical study (except at screening visit) within 4 weeks before study drug administration.
    • Blood transfusion within 4 weeks of study drug administration. h) Inability to tolerate oral medication.
    • Inability to be venipunctured performed and/or tolerate venous access.
    • Use of tobacco- or nicotine-containing products (including, but not limited to, cigarettes, pipes, e-cigarettes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months before check-in.
    • Drug or alcohol abuse (within 2 years of study drug administration) as defined in the Diagnostic and Statistical Manual of Mental Disorders - 4th Edition, Diagnostic Criteria for Drug and Alcohol Abuse History of glucose intolerance or diabetes mellitus.
    • For females, history of chronic or recurrent urinary tract infection (UTI) (defined as 3 occurrences per year) or UTI in the past 3 months. For males, any UTI within the previous 5 years that has not been thoroughly evaluated and for which an explanation is not clear.
    • History of recurrent (defined as 3 occurrences per year) or recent vulvovaginal mycotic infections.
    • Any other sound medical, psychiatric, and/or social reason as determined by the investigator.

    Physical and Laboratory Test Findings

    1. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECGs, or clinical laboratory determinations beyond what is consistent with the target population.
    2. Abnormal urinalysis at screening (may repeat once). If the urinalysis is abnormal on Day -1 of Period 1, continuation in the study is up to the investigator's discretion. The CRO medical monitor should be consulted.
    3. Glucosuria or hematoria at screening or Day -1 of Period 1, repeat is not permitted. d) A positive nicotine test (ie, cotinine).

    e) Abnormal liver function tests (alanine or aspartate aminotransferase [ALT or AST, respectively], or total bilirubin).

    f) Any of the following on 12-lead ECG prior to study drug administration, confirmed by repeat.

    i) PR ≥ 210 ms ii) QRS ≥ 120 ms iii) QT ≥ 500 ms iv) QTcF ≥ 450 ms g) Positive urine screen for drugs of abuse. h) Positive urine alcohol test. i) Positive blood screen for hepatitis C virus (HCV) antibody, hepatitis B surface antigen (HBsAg), or human immunodeficiency virus (HIV)-1 or HIV-2 antibodies at screening.

  4. Allergies and Adverse Drug Reaction

    1. History of allergy or adverse reactions to DPP4 or SGLT inhibitors or related compounds.
    2. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).
  5. Other Exclusion Criteria

    1. Prisoners or subjects who are involuntarily incarcerated.
    2. Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
    3. Inability to comply with restrictions and prohibited activities/treatments

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02223065


Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Michael Gartner, MD Celerion

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02223065    
Other Study ID Numbers: CV181-364
First Posted: August 22, 2014    Key Record Dates
Results First Posted: April 27, 2016
Last Update Posted: April 27, 2016
Last Verified: March 2016
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Saxagliptin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors