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

NCT00904176 | Completed Phase 1

• 1 other identifier: MB102-058
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Exposure to the investigational drug will be measured to compare with and without the co-administration of other drugs

  216 hours post-dose

Secondary Outcomes (2)

• 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

• 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

Study Arms (4)

Dapagliflozin + Warfarin

ACTIVE COMPARATOR

Drug: Dapagliflozin; Drug: Warfarin

Warfarin

ACTIVE COMPARATOR

Drug: Warfarin

Dapagliflozin + Digoxin

ACTIVE COMPARATOR

Drug: Dapagliflozin; Drug: Digoxin

Digoxin

ACTIVE COMPARATOR

Drug: Digoxin

Interventions

Dapagliflozin DRUG

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

Dapagliflozin + Digoxin; Dapagliflozin + Warfarin

Warfarin DRUG

Tablets, Oral, 25 mg, Single Dose

Also known as: Coumadin

Dapagliflozin + Warfarin; Warfarin

Digoxin DRUG

Tablets, Oral, 0.25, Single Dose

Also known as: Lanoxin

Dapagliflozin + Digoxin; Digoxin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Pra International

Lenexa, Kansas, 66219, United States

Location

Related Links

• MB102-058\_redacted \_CSR \_synopsis

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin; Warfarin; Digoxin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2009
• First Posted: May 19, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: October 17, 2016

Record last verified: 2016-10

Locations

US (1)