Study of the Effect of Dapagliflozin on the Pharmacokinetics of Warfarin or Digoxin in Healthy Subjects

NCT ID: NCT00904176

Last Updated: 2016-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2009-08-31

Brief Summary

The purpose of this study is determine that Dapagliflozin has no effect on the pharmacokinetics (PK) or pharmacodynamics (PD) of warfarin when dapagliflozin is coadministered with warfarin. Also, that Dapagliflozin has no effect on the PK of digoxin when dapagliflozin is coadministered with digoxin.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dapagliflozin + Warfarin

Group Type: ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type: DRUG

Tablets, Oral, 20 mg, followed by 10 mg, Single Dose

Warfarin

Intervention Type: DRUG

Tablets, Oral, 25 mg, Single Dose

Warfarin

Group Type: ACTIVE_COMPARATOR

Warfarin

Intervention Type: DRUG

Tablets, Oral, 25 mg, Single Dose

Dapagliflozin + Digoxin

Group Type: ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type: DRUG

Tablets, Oral, 20 mg, followed by 10 mg, Single Dose

Digoxin

Intervention Type: DRUG

Tablets, Oral, 0.25, Single Dose

Digoxin

Group Type: ACTIVE_COMPARATOR

Digoxin

Intervention Type: DRUG

Tablets, Oral, 0.25, Single Dose

Interventions

Dapagliflozin

Tablets, Oral, 20 mg, followed by 10 mg, Single Dose

Intervention Type: DRUG

Warfarin

Tablets, Oral, 25 mg, Single Dose

Intervention Type: DRUG

Digoxin

Tablets, Oral, 0.25, Single Dose

Intervention Type: DRUG

Other Intervention Names

Coumadin; Lanoxin

Eligibility 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
• Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) and men, ages 18 to 45

Exclusion Criteria

• WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal
• Any significant acute or chronic medical illness or relevant trauma (e.g. history of chronic hypertension, bacterial endocarditis, hemorrhagic stroke, motor vehicle accident resulting in significant head trauma or internal injuries)
• History of important arrhythmias as determined by the Investigator, including but not limited to ventricular fibrillation, ventricular tachycardia, A-V block, Wolff-Parkinson-White Syndrome, and sinus bradycardia (defined in this study as heart rate < 50 bpm based on vital signs and ECG performed within 21 days of Study Day 1)
• History or evidence of abnormal bleeding or coagulation disorder (e.g., history of prolonged bleeding during dental procedures, pregnancy delivery, previous surgery or injury) and/or having a first degree relative under 50 years of age with a history of abnormal bleeding or coagulation disorder per patient's report
• History of unexplained syncope
• Presence of external hemorrhoids with signs of rectal bleeding on physical exam
• Positive fecal occult blood (FOB), using the Hemoccult Sensa® assay (or equivalent), or hematuria (more than trace), unless deemed not clinically significant by the Investigator and Medical Monitor at screening or dosing
• Platelet count < 150,000 cells/µL at screening or dosing
• INR or aPTT values above the upper limit of normal (ULN) at screening or dosing
• Hemoglobin or hematocrit < LLN at screening or dosing
• Abnormal urinalysis at screening or dosing (repeat urinalysis may be allowed for positive hematuria in women)
• Glucosuria at screening or dosing
• Abnormal liver functions tests (ALT, AST or total bilirubin > 10% above ULN) at screening or dosing
• History of diabetes mellitus
• History of heart failure
• History of renal insufficiency
• History of recurrent (defined as 3 occurrences 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 B surface antigen, or HIV-1, -2 antibody
• Protein C or Protein S deficiency
• History of allergy to SGLT2 inhibitors or related compounds
• History of allergy to warfarin or related compounds
• History of allergy to digoxin or related compounds
• Prior exposure to dapagliflozin 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 or over-the-counter acid controllers or vitamin K containing products within 4 weeks prior to study drug administration

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bristol-Myers Squibb

Role: STUDY_DIRECTOR

Bristol-Myers Squibb

Locations

Pra International

Lenexa, Kansas, United States

Countries

United States

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3648&filename=MB102-058_redacted%20_CSR%20_synopsis.pdf

MB102-058\_redacted \_CSR \_synopsis

Other Identifiers

MB102-058

Identifier Type: -

Identifier Source: org_study_id