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

• Status: Completed
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: AstraZeneca
• Collaborator: Bristol-Myers Squibb
• Treatments: Bumetanide; Dapagliflozin

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