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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01103609
• Other study ID #: D1020C00027
• Status: Completed
• Phase: Phase 1
• First received: April 13, 2010
• Last updated: November 5, 2010
• Start date: April 2010
• Est. completion date: August 2010

Study information

• Verified date: November 2010
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Warfarin
Oral tablet od on Day 4
• Placebo
Oral tablet bd, stepwise increased
• AZD1656
Oral tablet bd, stepwise increased

Locations

Country	Name	City	State
United Kingdom	Research Site	London

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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.	No
Secondary	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	No