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

This study has been completed.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01103609
First received: April 13, 2010
Last updated: November 5, 2010
Last verified: November 2010
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: Warfarin
Drug: Placebo
Drug: AZD1656
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

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). [ Time Frame: Serial PK blood samples will be taken on days 4-10 during the treatment periods ] [ Designated as safety issue: No ]

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). [ Time Frame: Serial blood samples for warfarin PD measurements will be taken on days 4-10 during the treatment periods ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Safety assessments will be monitored throughout the study, from screening visit until follow up visit. ] [ Designated as safety issue: No ]
  • 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). [ Time Frame: Serial PK blood samples will be taken on days 4-10 during the treatment periods ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: April 2010
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01103609

Locations
United Kingdom
Research Site
London, United Kingdom
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Stanko Skrtic AstraZeneca
Principal Investigator: James Ritter, Prof Quintiles Drug Research Unit
Study Chair: Mirjana Kujacic AstraZeneca
  More Information

No publications provided

Responsible Party: MSD, AstraZeneca
ClinicalTrials.gov Identifier: NCT01103609     History of Changes
Other Study ID Numbers: D1020C00027
Study First Received: April 13, 2010
Last Updated: November 5, 2010
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:
Diabetes
Type 2
Warfarin
drug-drug interaction

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014