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Study to Evaluate the Potential Pharmacokinetic Interaction and Pharmacodynamic Effects on Renal Parameters of Bumetanide (1mg) and Dapagliflozin (10 mg) When Co-administered in Healthy Subjects

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT00930865
Collaborator
Bristol-Myers Squibb (Industry)
42
Enrollment
1
Location
3
Arms
2
Duration (Months)
20.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To assess the potential pharmacokinetic (PK) interactions of bumetanide and dapagliflozin following multiple doses of 1 mg bumetanide and 10 mg dapagliflozin in healthy subjects

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
42 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-Label, Parallel-group, Multiple-Dose Study to Evaluate the Potential Pharmacokinetic Interaction and Pharmacodynamic Effects on Renal Parameters of Bumetanide (1mg) and Dapagliflozin (10 mg) When Co-administered in Healthy Subjects
Study Start Date :
Jul 1, 2009
Actual Primary Completion Date :
Sep 1, 2009
Actual Study Completion Date :
Sep 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Bumetanide

Drug: Bumetanide
Tablets, Oral, 1 mg, Single Dose, 7 Days
Other Names:
  • Bumex

    		•
    Active Comparator: Dapagliflozin

    Drug: Dapagliflozin
    Tablets, Oral, 10 mg. Single Dose, 7 Days
    Other Names:
  • BMS-512148

    		•
    Active Comparator: Bumetanide + Dapagliflozin

    Drug: Bumetanide
    Tablets, Oral, 1 mg, Single Dose, 7 Days
    Other Names:
  • Bumex

    • Drug: Dapagliflozin
    Tablets, Oral, 10 mg. Single Dose, 7 Days
    Other Names:
  • BMS-512148

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs [24 hours post-dose on Day 8 and 15]

    Secondary Outcome Measures

    1. To assess the safety and tolerability of bumetanide and dapagliflozin following multiple oral doses of 1 mg bumetanide and 10 mg dapagliflozin, administered together, either simultaneously or after adaptation to either agent alone, in healthy subjects [during 14 days of dosing]

    2. Explore potential pharmacodynamic (serum/urine electrolytes) effects of bumetanide + dapagliflozin following multiple doses of 1 mg bumetanide + 10 mg dapagliflozin, administered together, either simultaneously or after adaptation to either agent alone [during 14 days of dosing]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, ECGs, and clinical laboratory determinations

    • Body Mass Index (BMI) of 18 to 32 kg/m², inclusive. BMI = weight (kg)/ [height (m)]²

    • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized and men, ages 18 to 45

    Exclusion Criteria:

    • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period

    • Any significant acute or chronic medical illness

    • Current or recent (within 3 months) gastrointestinal disease

    • Current smoker or recent (within 1 month) history of regular tobacco use

    • Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population

    • Abnormal urinalysis at screening

    • Glucosuria at screening

    • Abnormal liver functions tests (ALT, AST or total bilirubin > 10 % ULN)

    • Presence of edema on physical exam

    • History of diabetes mellitus

    • History of heart failure

    • History of renal insufficiency

    • History of chronic or recurrent UTI (defined as 3 occurrences per year) or UTI in the past 3 months

    • Positive urine screen for drugs of abuse either at screening or before dosing

    • Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibody

    • History of allergy to SGLT2 inhibitors, bumetanide (or related compounds)

    • History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)

    • Prior exposure to dapagliflozin within 3 months of Day -1

    • Exposure to any investigational drug or placebo within 4 weeks of Day -1

    • Use of any prescription drugs within 4 weeks or over-the-counter acid controllers within 2 weeks prior to study drug administration

    • Use of any other drugs, including over-the-counter medications within 1 week and herbal preparations, within 2 weeks prior to study drug administration

    • Use of an oral, injectable or implantable hormonal contraceptive agent within 3 months of study drug administration

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ppd Development, Lp Austin Texas United States 78744

    Sponsors and Collaborators

    • AstraZeneca
    • Bristol-Myers Squibb

    Investigators

    • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT00930865
    Other Study ID Numbers:
    • MB102-057
    First Posted:
    Jul 2, 2009
    Last Update Posted:
    Oct 17, 2016
    Last Verified:
    Oct 1, 2016
    Additional relevant MeSH terms:
    Diabetes Mellitus, Type 2
    Dapagliflozin
    Bumetanide

    Study Results

    No Results Posted as of Oct 17, 2016