Clinical trial NCT01103609: Investigate the Effect of AZD1656 on the Pharmacokinetics and Pharmacodynamics of Warfarin in Type 2 Diabetes Mellitus (T2DM) Patients
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes
Type 2
Warfarin
drug-drug interaction
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-04-14
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: Serial PK blood samples will be taken on days 4-10 during the treatment periods
Secondary outcomes:
measure: To evaluate the anticoagulant activity of warfarin upon co-administration with AZD1656 by assessment of prothrombin time (PT) and international normalised ratio (INR).
timeFrame: Serial blood samples for warfarin PD measurements will be taken on days 4-10 during the treatment periods
measure: 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
timeFrame: Safety assessments will be monitored throughout the study, from screening visit until follow up visit.
measure: 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).
timeFrame: Serial PK blood samples will be taken on days 4-10 during the treatment periods
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: Stanko Skrtic
role: STUDY_DIRECTOR
affiliation: Quintiles Drug Research Unit
name: James Ritter, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Mirjana Kujacic
role: STUDY_CHAIR
References: