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

October 14, 2016 updated by: AstraZeneca

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

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

Study Overview

Status

Completed

Study Type

Interventional

Enrollment (Actual)

42

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Texas
      • Austin, Texas, United States, 78744
        • PPD Development, LP

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Bumetanide
Tablets, Oral, 1 mg, Single Dose, 7 Days
Other Names:
  • Bumex
ACTIVE_COMPARATOR: Dapagliflozin
Tablets, Oral, 10 mg. Single Dose, 7 Days
Other Names:
  • BMS-512148
ACTIVE_COMPARATOR: Bumetanide + Dapagliflozin
Tablets, Oral, 1 mg, Single Dose, 7 Days
Other Names:
  • Bumex
Tablets, Oral, 10 mg. Single Dose, 7 Days
Other Names:
  • BMS-512148

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs
Time Frame: 24 hours post-dose on Day 8 and 15
24 hours post-dose on Day 8 and 15

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: during 14 days of dosing
during 14 days of dosing
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
Time Frame: during 14 days of dosing
during 14 days of dosing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Collaborators

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (ACTUAL)

September 1, 2009

Study Completion (ACTUAL)

September 1, 2009

Study Registration Dates

First Submitted

June 30, 2009

First Submitted That Met QC Criteria

June 30, 2009

First Posted (ESTIMATE)

July 2, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

October 17, 2016

Last Update Submitted That Met QC Criteria

October 14, 2016

Last Verified

October 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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