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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00839683
• Other study ID #: MB102-036
• Status: Completed
• Phase: Phase 1
• First received: February 5, 2009
• Last updated: October 14, 2016
• Start date: February 2009
• Est. completion date: March 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

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: March 2009
• Est. primary completion date: March 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

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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• simvastatin
Tablets, Oral, 20 mg, Single Dose
• Dapagliflozin
Tablets, Oral, 20 mg, Single Dose
• simvastatin
Oral, 40 mg, Single Dose
• valsartan
Tablets, Oral, 320 mg, Single Dose

Locations

Country	Name	City	State
United States	Mds Pharma Services (Us) Inc.	Neptune	New Jersey

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		72 hours post-dose	No
Secondary	To assess the safety and tolerability of dapagliflozin when administered alone, with valsartan, or with simvastatin in healthy subjects		15 timepoints	Yes
Secondary	To assess the safety and tolerability of the combination of dapagliflozin with valsartan, and the combination of dapagliflozin with simvastatin in healthy subjects		15 timepoints	Yes
Secondary	To assess the effect of dapagliflozin on the PK of simvastatin acid (active metabolite of simvastatin), when coadministered in healthy subjects		15 timepoints	No

External Links

•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   MB102-036_redacted _CSR _synopsis