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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00930865
• Other study ID #: MB102-057
• Status: Completed
• Phase: Phase 1
• First received: June 30, 2009
• Last updated: October 14, 2016
• Start date: July 2009
• Est. completion date: September 2009

Study information

• Verified date: October 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Bumetanide
Tablets, Oral, 1 mg, Single Dose, 7 Days
• Dapagliflozin
Tablets, Oral, 10 mg. Single Dose, 7 Days

Locations

Country	Name	City	State
United States	Ppd Development, Lp	Austin	Texas

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	Yes

External Links

•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   MB102-057_redacted _CSR _synopsis