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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

This study has been completed.
Sponsor:
Collaborator:
AstraZeneca
Information provided by:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00930865
First received: June 30, 2009
Last updated: February 22, 2011
Last verified: November 2009
History of Changes
  Purpose

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 Intervention Phase
Type 2 Diabetes Mellitus
 Drug: Bumetanide
Drug: Dapagliflozin
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:

Drug Information available for: Bumetanide
U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: July 2009
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Bumetanide Drug: Bumetanide
Tablets, Oral, 1 mg, Single Dose, 7 Days
Other Name: Bumex
Active Comparator: Dapagliflozin Drug: Dapagliflozin
Tablets, Oral, 10 mg. Single Dose, 7 Days
Other Name: BMS-512148
Active Comparator: Bumetanide + Dapagliflozin Drug: Bumetanide
Tablets, Oral, 1 mg, Single Dose, 7 Days
Other Name: Bumex
Drug: Dapagliflozin
Tablets, Oral, 10 mg. Single Dose, 7 Days
Other Name: BMS-512148

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00930865

Locations
United States, Texas
Ppd Development, Lp
Austin, Texas, United States, 78744
Sponsors and Collaborators
Bristol-Myers Squibb
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
BMS Clinical Trials Disclosure  This link exits the ClinicalTrials.gov site
Investigator Inquiry form  This link exits the ClinicalTrials.gov site
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00930865     History of Changes
Other Study ID Numbers: MB102-057
Study First Received: June 30, 2009
Last Updated: February 22, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Bumetanide
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 18, 2013