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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This study has been withdrawn prior to enrollment.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
History of Changes
  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: Endpoint Classification: Safety Study
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:

U.S. FDA Resources

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 1 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 2 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 3 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 4 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 5 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 6 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 7 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 8 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 9 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 10 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 11 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 12 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 13 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 14 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 15 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 16 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 17 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 18 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 19 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 20 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 21 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 22 ] [ Designated as safety issue: No ]
  • Pharmacodynamics measured by maximum international normalised ratio ( INRmax) [ Time Frame: International normalised ratio (INR) sampling will be performed day 23 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetics for AZD9668 measured by Css,max [ Time Frame: Range from day 9 to 23 ] [ Designated as safety issue: No ]
  • Pharmacokinetics for AZD9668 measured by tss,max [ Time Frame: Range from day 9 to 23 ] [ Designated as safety issue: No ]
  • Pharmacokinetics for AZD9668 measured by Css,min [ Time Frame: Range from day 9 to 23 ] [ Designated as safety issue: No ]
  • Pharmacokinetics for AZD9668 measured by CLss/F [ Time Frame: Range from day 9 to 23 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics for (R)- and (S)- Warfarin measured tmax. [ Time Frame: Range from day 1 to 23 ] [ Designated as safety issue: No ]
  • Pharmacokinetics for (R)- and (S)- Warfarin measured t½. [ Time Frame: Range from day 1 to 23 ] [ Designated as safety issue: No ]
  • Pharmacokinetics for (R)- and (S)- Warfarin measured CL/F. [ Time Frame: Range from day 1 to 23 ] [ Designated as safety issue: No ]
  • Pharmacokinetics for (R)- and (S)- Warfarin measured Vz/F. [ Time Frame: Range from day 1 to 23 ] [ Designated as safety issue: No ]

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
Genders 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
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

No publications provided

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
Health Authority: Sweden: Medical Products Agency

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
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013