NCT01214122

Brief Summary

The primary purpose of this study is to determine whether the treatment with AZD9668 will affect the metabolism and effect of Warfarin.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Nov 2010

Shorter than P25 for phase_1

Geographic Reach
1 country

2 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 21, 2010

Completed
13 days until next milestone

First Posted

Study publicly available on registry

October 4, 2010

Completed
28 days until next milestone

Study Start

First participant enrolled

November 1, 2010

Completed
1 month until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2010

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2010

Completed
Last Updated

January 29, 2013

Status Verified

January 1, 2013

Enrollment Period

1 month

First QC Date

September 21, 2010

Last Update Submit

January 28, 2013

Conditions

PharmacokineticsPharmacodynamics

Keywords

Phase 1Drug-Drug interactionwarfarinAZD9668resulting from AZD9668 and Warfarin interactionpharmacokineticspharmacodynamics

Outcome Measures

Primary Outcomes (46)

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 1

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 2

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 3

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 4

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 5

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 6

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 7

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 8

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 9

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 10

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 11

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 12

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 13

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 14

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 15

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 16

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 17

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 18

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 19

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 20

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 21

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 22

  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)

    Pharmacokinetic (PK) sampling will be performed day 23

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 1

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 2

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 3

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 4

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 5

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 6

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 7

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 8

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 9

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 10

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 11

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 12

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 13

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 14

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 15

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 16

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 17

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 18

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 19

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 20

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 21

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 22

  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax)

    International normalised ratio (INR) sampling will be performed day 23

Secondary Outcomes (10)

  • Pharmacokinetics for AZD9668 measured by Css,max

    Range from day 9 to 23

  • Pharmacokinetics for AZD9668 measured by tss,max

    Range from day 9 to 23

  • Pharmacokinetics for AZD9668 measured by Css,min

    Range from day 9 to 23

  • Pharmacokinetics for AZD9668 measured by CLss/F

    Range from day 9 to 23

  • Severity of Adverse Events as a Measure of Safety and Tolerability

    Adverse events will be collected pre-dose, during treatment and at follow up

  • +5 more secondary outcomes

Study Arms (2)

Treatment A

EXPERIMENTAL

AZD9668 - 2 x30mg tablets

Drug: AZD9668

Treatment B

EXPERIMENTAL

Warfarin - 10 x2.5 mg tablets

Drug: Warfarin

Interventions

AZD9668DRUG

60 mg orally twice daily for 11 days

Treatment A
WarfarinDRUG

10 x 2.5 (25) mg orally once daily on day 1 and on day 14

Treatment B

Eligibility Criteria

Age18 Years - 55 Years
Sexmale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Provision of signed informed consent (including genotyping screening sample for CYP2C9 and VKORC1) prior to any study specific procedures
  • Subjects must be willing to use a barrier method of contraception, unless their partners are post-menopausal or surgically sterile, or if a female partner is of childbearing potential the subject must use a barrier method of contraception (condom) and the partner must use accepted contraceptive methods (oral contraceptive, implant, long term injectable contraceptive or intrauterine device), from first dose of IP (warfarin and AZD9668) until 3 months after last dose of IP (warfarin and AZD9668)
  • Have a body mass index between 19 and 30 kg/m2 (inclusive) and a weight between 50 and 100 kg (inclusive)
  • Be a non-smoker or ex-smoker who has stopped smoking for \>6 months prior to Visit 1.

You may not qualify if:

  • Any clinically significant disease or disorder
  • Subject predicted to have high sensitivity to warfarin based on CYP2C9 and VKORC1 genotypes
  • Any clinically relevant abnormal findings in physical examination

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Research Site

Linköping, Sweden

Location

Research Site

Uppsala, Sweden

Location

MeSH Terms

Interventions

N-((5-(methanesulfonyl)pyridin-2-yl)methyl)-6-methyl-5-(1-methyl-1H-pyrazol-5-yl)-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamideWarfarin

Intervention Hierarchy (Ancestors)

4-HydroxycoumarinsCoumarinsBenzopyransPyransHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Christopher D O'Brien, MD, PhD

    AstraZeneca R&D

    STUDY DIRECTOR

  • Ingemar Bylesjö, MD

    Berzelius Clinical Reseach Centre

    PRINCIPAL INVESTIGATOR

  • Wolfgang Kühn, MD

    Quintiles AB, Phase 1 Services

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Masking
NONE
Purpose
BASIC SCIENCE
Sponsor Type
INDUSTRY

Study Record Dates

First Submitted

September 21, 2010

First Posted

October 4, 2010

Study Start

November 1, 2010

Primary Completion

December 1, 2010

Study Completion

December 1, 2010

Last Updated

January 29, 2013

Record last verified: 2013-01

Locations

SE(2)