Clinical trial NCT00839683: Pharmacokinetic Drug Interaction Study of Dapagliflozin and Valsartan or Simvastatin in Healthy Subjects
Official title: Pharmacokinetic Drug Interaction Study of Dapagliflozin and Valsartan or Simvastatin in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2009-02-09
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: Phase A - To assess the effect of simvastatin on the pharmacokinetics (PK) of dapagliflozin and to determine the effect of dapagliflozin on the PK of simvastatin, when simvastatin and dapagliflozin are coadministered in healthy subjects. Phase B - To assess the effect of valsartan on the PK of dapagliflozin and to determine the effect of dapagliflozin on the PK of valsartan, when valsartan and dapagliflozin are coadministered in healthy subjects


Eligibility 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

Exclusion Criteria:

* Women of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of investigational product
* Abnormal urinalysis at screening (repeat urinalysis may be allowed for positive hematuria in women)
* Glucosuria at screening
* Abnormal liver functions tests (ALT, AST or total bilirubin \> 10% above 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
* History of recurrent (defined as 3 occurences per year) or recent vulvovaginal mycotic infections
* Positive urine screen for drugs of abuse either at screening or before dosing
* Positive blood screen for hepatitis C antibody, hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibody
* History of allergy to SGLT2 inhibitors or related compounds
* History of any significant drug allergy (such as anaphylaxis or hepatotoxicity)
* History of allergy or intolerance to valsartan or simvastatin (or related compounds)
* Prior exposure to dapagliflozin, valsartan or simvastatin 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 any study drug administration
* Use of any other drugs, including over-the counter medications within 1 week and herbal preparations within 2 weeks prior to admission to the study facility
* Use of an oral, injectable or implantable hormonal contraceptive agent within 3 months of Day -1

Primary outcomes:
measure: Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs
timeFrame: 72 hours post-dose
Secondary outcomes:
measure: To assess the safety and tolerability of dapagliflozin when administered alone, with valsartan, or with simvastatin in healthy subjects
timeFrame: 15 timepoints
measure: To assess the safety and tolerability of the combination of dapagliflozin with valsartan, and the combination of dapagliflozin with simvastatin in healthy subjects
timeFrame: 15 timepoints
measure: To assess the effect of dapagliflozin on the PK of simvastatin acid (active metabolite of simvastatin), when coadministered in healthy subjects
timeFrame: 15 timepoints
Other outcomes:
Locations:
city: Neptune
country: United States
facility: Mds Pharma Services (Us) Inc.
state: New Jersey
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References: