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A Drug-Drug Interaction Study Between AZD9668 and Warfarin to Study the Effect of AZD9668 on the Metabolism and Effect of Warfarin

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01214122
First received: September 21, 2010
Last updated: January 28, 2013
Last verified: January 2013
  Purpose
The primary purpose of this study is to determine whether the treatment with AZD9668 will affect the metabolism and effect of Warfarin.

Condition Intervention Phase
Pharmacokinetics
Pharmacodynamics
Drug: AZD9668
Drug: Warfarin
Phase 1

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase I, Open Label, Fixed Sequence, Single Centre Study in Healthy Volunteers to Investigate the Effects of Repeated Oral Doses AZD9668 on the Pharmacokinetics and Pharmacodynamics of a Single Dose of Warfarin

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Pharmacokinetic (PK) sampling will be performed day 23 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 1 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 2 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 3 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 4 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 5 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 6 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 7 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 8 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 9 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 10 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 11 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 12 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 13 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 14 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 15 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 16 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 17 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 18 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 19 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 20 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 21 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 22 ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 23 ]

Secondary Outcome Measures:
  • Pharmacokinetics for AZD9668 measured by Css,max [ Time Frame: Range from day 9 to 23 ]
  • Pharmacokinetics for AZD9668 measured by tss,max [ Time Frame: Range from day 9 to 23 ]
  • Pharmacokinetics for AZD9668 measured by Css,min [ Time Frame: Range from day 9 to 23 ]
  • Pharmacokinetics for AZD9668 measured by CLss/F [ Time Frame: Range from day 9 to 23 ]
  • Severity of Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Adverse events will be collected pre-dose, during treatment and at follow up ]
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Adverse events will be collected pre-dose, during treatment and at follow up ]
  • Pharmacokinetics for (R)- and (S)- Warfarin measured tmax. [ Time Frame: Range from day 1 to 23 ]
  • Pharmacokinetics for (R)- and (S)- Warfarin measured t½. [ Time Frame: Range from day 1 to 23 ]
  • Pharmacokinetics for (R)- and (S)- Warfarin measured CL/F. [ Time Frame: Range from day 1 to 23 ]
  • Pharmacokinetics for (R)- and (S)- Warfarin measured Vz/F. [ Time Frame: Range from day 1 to 23 ]

Enrollment: 0
Study Start Date: November 2010
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
AZD9668 - 2 x30mg tablets
Drug: AZD9668
60 mg orally twice daily for 11 days
Experimental: Treatment B
Warfarin - 10 x2.5 mg tablets
Drug: Warfarin
10 x 2.5 (25) mg orally once daily on day 1 and on day 14

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01214122

Locations
Sweden
Research Site
Linköping, Sweden
Research Site
Uppsala, Sweden
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Christopher D O'Brien, MD, PhD AstraZeneca R&D
Principal Investigator: Ingemar Bylesjö, MD Berzelius Clinical Reseach Centre
Principal Investigator: Wolfgang Kühn, MD Quintiles AB, Phase 1 Services
  More Information

Responsible Party: Medical Science Director, AstraZeneca
ClinicalTrials.gov Identifier: NCT01214122     History of Changes
Other Study ID Numbers: D0520C00013  2010-022360-12 
Study First Received: September 21, 2010
Last Updated: January 28, 2013

Keywords provided by AstraZeneca:
Phase 1
Drug-Drug interaction
warfarin
AZD9668
resulting from AZD9668 and Warfarin interaction
pharmacokinetics
pharmacodynamics

Additional relevant MeSH terms:
Warfarin
Anticoagulants

ClinicalTrials.gov processed this record on February 23, 2017