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

NCT01103609 | Completed Phase 1

• 1 other identifier: D1020C00027
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes; Type 2; Warfarin; drug-drug interaction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

1

EXPERIMENTAL

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

Drug: Warfarin; Drug: AZD1656

2

PLACEBO COMPARATOR

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

Drug: Warfarin; Drug: Placebo

Interventions

Warfarin DRUG

Oral tablet od on Day 4

1; 2

Placebo DRUG

Oral tablet bd, stepwise increased

2

AZD1656 DRUG

Oral tablet bd, stepwise increased

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

London, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Interventions

Warfarin; AZD1656

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Stanko Skrtic

  AstraZeneca

  STUDY DIRECTOR

• James Ritter, Prof

  Quintiles Drug Research Unit

  PRINCIPAL INVESTIGATOR

• Mirjana Kujacic

  AstraZeneca

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 13, 2010
• First Posted: April 14, 2010
• Study Start: April 1, 2010
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2010
• Last Updated: November 8, 2010

Record last verified: 2010-11

Locations

GB (1)