Pharmacokinetic Drug Interaction Study of Dapagliflozin and Valsartan or Simvastatin in Healthy Subjects

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: simvastatin; Drug: Dapagliflozin; Drug: valsartan

Study type: Interventional

Funder types: Industry

Identifiers

NCT00839683

MB102-036

Details and patient eligibility

About

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

Enrollment: 24 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

24 participants in 5 patient groups

simvastatin

Active Comparator group

Treatment:

Drug: simvastatin

Drug: simvastatin

Dapagliflozin + simvastatin

Active Comparator group

Treatment:

Drug: simvastatin

Drug: Dapagliflozin

Drug: simvastatin

Dapagliflozin

Active Comparator group

Treatment:

Drug: Dapagliflozin

valsartan

Active Comparator group

Treatment:

Drug: valsartan

Dapagliflozin + valsartan

Active Comparator group

Treatment:

Drug: valsartan

Drug: Dapagliflozin