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

Phase 1

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Warfarin; Drug: AZD1656; Drug: Placebo

• Registration Number: NCT01103609
• Lead Sponsor: AstraZeneca

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04
• Study First Submitted: 2010-04-13
• Study First Submitted QC: 2010-04-13
• Study First Posted: 2010-04-14
• Primary Completion: 2010-08
• Study Completion: 2010-08
• Status Verified: 2010-11
• Last Update Submitted: 2010-11-05
• Last Update Posted: 2010-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	Warfarin	twice daily on Day 1 to Day 10, with Warfarin on Day 4
1	AZD1656	twice daily on Day 1 to Day 10, with Warfarin on Day 4
2	Warfarin	twice daily on Day 1 to Day 10, with Warfarin on Day 4
2	Placebo	twice daily on Day 1 to Day 10, with Warfarin on Day 4

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

Research Site; 🇬🇧 London, United Kingdom