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

Condition(s) targeted: Type 2 Diabetes Mellitus

Intervention: simvastatin (Drug); Dapagliflozin (Drug); simvastatin (Drug); valsartan (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: AstraZeneca

Official(s) and/or principal investigator(s):
Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb

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

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

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Primary outcome: Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs

Secondary outcome:

To assess the safety and tolerability of dapagliflozin when administered alone, with valsartan, or with simvastatin in healthy subjects

To assess the safety and tolerability of the combination of dapagliflozin with valsartan, and the combination of dapagliflozin with simvastatin in healthy subjects

To assess the effect of dapagliflozin on the PK of simvastatin acid (active metabolite of simvastatin), when coadministered in healthy subjects

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

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

Mds Pharma Services (Us) Inc., Neptune, New Jersey 07753, United States

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Starting date: February 2009
Last updated: March 20, 2015