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

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01103609

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Warfarin Drug: Placebo Drug: AZD1656	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2010

Actual Primary Completion Date :

Aug 1, 2010

Actual Study Completion Date :

Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 twice daily on Day 1 to Day 10, with Warfarin on Day 4	Drug: Warfarin Oral tablet od on Day 4 Drug: AZD1656 Oral tablet bd, stepwise increased
Placebo Comparator: 2 twice daily on Day 1 to Day 10, with Warfarin on Day 4	Drug: Warfarin Oral tablet od on Day 4 Drug: Placebo Oral tablet bd, stepwise increased

Arm

Intervention/Treatment

Experimental: 1

twice daily on Day 1 to Day 10, with Warfarin on Day 4

Drug: Warfarin

Oral tablet od on Day 4

Drug: AZD1656

Oral tablet bd, stepwise increased

Placebo Comparator: 2

twice daily on Day 1 to Day 10, with Warfarin on Day 4

Drug: Warfarin

Oral tablet od on Day 4

Drug: Placebo

Oral tablet bd, stepwise increased

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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