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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Dapagliflozin; Drug: simvastatin; Drug: simvastatin; Drug: valsartan

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dapagliflozin	Drug: Dapagliflozin; Tablets, Oral, 20 mg, Single Dose; Other Names: BMS-512148
Active Comparator: valsartan	Drug: valsartan; Tablets, Oral, 320 mg, Single Dose; Other Names: Diovan
Active Comparator: simvastatin	Drug: simvastatin; Tablets, Oral, 20 mg, Single Dose; Other Names: Zocor; Drug: simvastatin; Oral, 40 mg, Single Dose
Active Comparator: Dapagliflozin + simvastatin	Drug: Dapagliflozin; Tablets, Oral, 20 mg, Single Dose; Other Names: BMS-512148; Drug: simvastatin; Tablets, Oral, 20 mg, Single Dose; Other Names: Zocor; Drug: simvastatin; Oral, 40 mg, Single Dose
Active Comparator: Dapagliflozin + valsartan	Drug: Dapagliflozin; Tablets, Oral, 20 mg, Single Dose; Other Names: BMS-512148; Drug: valsartan; Tablets, Oral, 320 mg, Single Dose; Other Names: Diovan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs	72 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the safety and tolerability of dapagliflozin when administered alone, with valsartan, or with simvastatin in healthy subjects	15 timepoints
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
To assess the effect of dapagliflozin on the PK of simvastatin acid (active metabolite of simvastatin), when coadministered in healthy subjects	15 timepoints

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• MB102-036_redacted _CSR _synopsis

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: February 5, 2009
• First Submitted That Met QC Criteria: February 6, 2009
• First Posted (Estimate): February 9, 2009

Study Record Updates

• Last Update Posted (Estimate): October 17, 2016
• Last Update Submitted That Met QC Criteria: October 14, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Dapagliflozin; Valsartan; Simvastatin
• Other Study ID Numbers: MB102-036