Pharmacokinetic Drug Interaction Study of Dapagliflozin and Valsartan or Simvastatin in Healthy Subjects - Full Text View

Sponsor:	Bristol-Myers Squibb
Collaborator:	AstraZeneca
Information provided by:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00839683

Purpose

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

Condition	Intervention	Phase
Type 2 Diabetes Mellitus	Drug: simvastatin Drug: Dapagliflozin Drug: valsartan	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label
Official Title:	Pharmacokinetic Drug Interaction Study of Dapagliflozin and Valsartan or Simvastatin in Healthy Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: 6q24-related transient neonatal diabetes mellitus

MedlinePlus related topics: Diabetes Diabetes Type 2 Drug Reactions

Drug Information available for: Simvastatin Valsartan BMS 512148

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs [ Time Frame: 72 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the safety and tolerability of dapagliflozin when administered alone, with valsartan, or with simvastatin in healthy subjects [ Time Frame: 15 timepoints ] [ Designated as safety issue: Yes ]
To assess the safety and tolerability of the combination of dapagliflozin with valsartan, and the combination of dapagliflozin with simvastatin in healthy subjects [ Time Frame: 15 timepoints ] [ Designated as safety issue: Yes ]
To assess the effect of dapagliflozin on the PK of simvastatin acid (active metabolite of simvastatin), when coadministered in healthy subjects [ Time Frame: 15 timepoints ] [ Designated as safety issue: No ]

Enrollment:	24
Study Start Date:	February 2009
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: simvastatin	Drug: simvastatin Tablets, Oral, 20 mg, Single Dose Other Name: Zocor
Active Comparator: Dapagliflozin + simvastatin	Drug: Dapagliflozin Tablets, Oral, 20 mg, Single Dose Other Name: BMS-512148 Drug: simvastatin Oral, 40 mg, Single Dose
Active Comparator: Dapagliflozin	Drug: Dapagliflozin Tablets, Oral, 20 mg, Single Dose Other Name: BMS-512148
Active Comparator: valsartan	Drug: valsartan Tablets, Oral, 320 mg, Single Dose Other Name: Diovan
Active Comparator: Dapagliflozin + valsartan	Drug: Dapagliflozin Tablets, Oral, 20 mg, Single Dose Other Name: BMS-512148 Drug: valsartan Tablets, Oral, 320 mg, Single Dose Other Name: Diovan

Eligibility

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00839683

Locations

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

Sponsors and Collaborators

Bristol-Myers Squibb

AstraZeneca

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00839683 History of Changes
Other Study ID Numbers:	MB102-036
Study First Received:	February 5, 2009
Last Updated:	February 22, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Simvastatin
Valsartan
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Antihypertensive Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on February 09, 2012