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

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00904176
First received: May 18, 2009
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Dapagliflozin
Drug: Warfarin
Drug: Digoxin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study of the Effect of Dapagliflozin on the Pharmacokinetics of Warfarin or Digoxin in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs [ Time Frame: 216 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the effect of dapagliflozin on the PK of R-warfarin, when warfarin and dapagliflozin are coadministered in healthy subjects (Cohort 1) [ Time Frame: 16 time points ] [ Designated as safety issue: Yes ]
  • To assess the safety and tolerability of the combination of dapagliflozin with warfarin, and the combination of dapagliflozin with digoxin in healthy subjects [ Time Frame: 16 time points ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: June 2009
Study Completion Date: August 2009
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Dapagliflozin + Warfarin Drug: Dapagliflozin
Tablets, Oral, 20 mg, followed by 10 mg, Single Dose
Drug: Warfarin
Tablets, Oral, 25 mg, Single Dose
Other Name: Coumadin
Active Comparator: Warfarin Drug: Warfarin
Tablets, Oral, 25 mg, Single Dose
Other Name: Coumadin
Active Comparator: Dapagliflozin + Digoxin Drug: Dapagliflozin
Tablets, Oral, 20 mg, followed by 10 mg, Single Dose
Drug: Digoxin
Tablets, Oral, 0.25, Single Dose
Other Name: Lanoxin
Active Comparator: Digoxin Drug: Digoxin
Tablets, Oral, 0.25, Single Dose
Other Name: Lanoxin

  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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00904176

Locations
United States, Kansas
Pra International
Lenexa, Kansas, United States, 66219
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00904176     History of Changes
Other Study ID Numbers: MB102-058
Study First Received: May 18, 2009
Last Updated: June 6, 2014
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
Warfarin
Digoxin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Arrhythmia Agents
Cardiovascular Agents
Cardiotonic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014