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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00904176
• Other study ID #: MB102-058
• Status: Completed
• Phase: Phase 1
• First received: May 18, 2009
• Last updated: October 14, 2016
• Start date: June 2009
• Est. completion date: August 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2009
• Est. primary completion date: August 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

• 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

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Dapagliflozin
Tablets, Oral, 20 mg, followed by 10 mg, Single Dose
• Warfarin
Tablets, Oral, 25 mg, Single Dose
• Digoxin
Tablets, Oral, 0.25, Single Dose

Locations

Country	Name	City	State
United States	Pra International	Lenexa	Kansas

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		216 hours post-dose	No
Secondary	To assess the effect of dapagliflozin on the PK of R-warfarin, when warfarin and dapagliflozin are coadministered in healthy subjects (Cohort 1)		16 time points	Yes
Secondary	To assess the safety and tolerability of the combination of dapagliflozin with warfarin, and the combination of dapagliflozin with digoxin in healthy subjects		16 time points	Yes

External Links

•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   MB102-058_redacted _CSR _synopsis