Type 2 Diabetes Mellitus
Conditions
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
Interventions
DRUGBumetanide
Tablets, Oral, 1 mg, Single Dose, 7 Days
DRUGDapagliflozin
Tablets, Oral, 10 mg. Single Dose, 7 Days
Sponsors
Bristol-Myers Squibb
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| 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 | 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 | during 14 days of dosing |
Countries
United States
Outcome results
None listed