Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, Type 2, Warfarin, drug-drug interaction
Brief summary
The purpose of this study is to determine whether AZD1656 will affect the Pharmacokinetics and Pharmacodynamics of Warfarin in T2DM patients.
Interventions
DRUGWarfarin
Oral tablet od on Day 4
DRUGPlacebo
Oral tablet bd, stepwise increased
DRUGAZD1656
Oral tablet bd, stepwise increased
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of T2DM treated with at least 1000 mg metformin as a single treatment or in combination with one other oral anti-diabetics for at least 2 months prior to screening. Doses of anti-diabetic treatment stable for at least 1 month * Fasting plasma glucose (FPG) at screening in the range of 6.0 to 15.0 mmol/L (108 to 270 mg/dL) and FPG in the range of 7.5 to 13.0 mmol/L (135 to 234 mg/dL) on Day 1 * Haemoglobin (Hb) A1c \>6.5% at screening
Exclusion criteria
* Use of drugs with anticoagulant effects 3 weeks prior to first warfarin dosing * Use of amiodarone within 3 months prior to screening and the use of potent CYP450 inhibitors * Previous treatment with warfarin on clinical indication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the pharmacokinetics of warfarin after a single dose when administered alone and in combination with AZD1656 at steady state by assessment of AUC and Cmax of both enantiomers of warfarin (S- and R-warfarin). | Serial PK blood samples will be taken on days 4-10 during the treatment periods |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the anticoagulant activity of warfarin upon co-administration with AZD1656 by assessment of prothrombin time (PT) and international normalised ratio (INR). | Serial blood samples for warfarin PD measurements will be taken on days 4-10 during the treatment periods |
| To evaluate the safety of AZD1656 in combination with warfarin by assessment of electrocardiogram, weight, pulse, blood pressure, laboratory variables (including 7-point glucose), physical examination and adverse events | Safety assessments will be monitored throughout the study, from screening visit until follow up visit. |
| To describe the pharmacokinetics of AZD1656 and its metabolite during concomitant warfarin administration by assessment of AUC0-24, Cmax, Ctrough, tmax, t1/2 and CL/F (AZD1656 only). | Serial PK blood samples will be taken on days 4-10 during the treatment periods |
Countries
United Kingdom
Outcome results
None listed