Investigate the Effect of AZD1656 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Type 2 Diabetes Mellitus (T2DM) Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether AZD1656 will affect the Pharmacokinetics and Pharmacodynamics of Warfarin in T2DM patients.

Official Title
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An Open-Label, Randomised, Placebo-Controlled, Two-Way Crossover, Phase I Single Centre Study in Type 2 Diabetes Mellitus Patients Treated With Metformin to Evaluate the Pharmacokinetics and Pharmacodynamics of Warfarin During Co-administration With AZD1656

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Warfarin
* Drug: Placebo
* Drug: AZD1656


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>twice daily on Day 1 to Day 10, with Warfarin on Day 4 | Drug: Warfarin<br>* Oral tablet od on Day 4<br>Drug: AZD1656<br>* Oral tablet bd, stepwise increased<br>|
| Placebo Comparator: 2<br>twice daily on Day 1 to Day 10, with Warfarin on Day 4 | Drug: Warfarin<br>* Oral tablet od on Day 4<br>Drug: Placebo<br>* Oral tablet bd, stepwise increased<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, Type 2, Warfarin, drug-drug interaction