Clinical trial NCT01214122: A Drug-Drug Interaction Study Between AZD9668 and Warfarin to Study the Effect of AZD9668 on the Metabolism and Effect of Warfarin
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Pharmacokinetics
Pharmacodynamics
Keywords: Phase 1
Drug-Drug interaction
warfarin
AZD9668
resulting from AZD9668 and Warfarin interaction
pharmacokinetics
pharmacodynamics
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-10-04
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Primary purpose: BASIC_SCIENCE

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


Eligibility 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

Primary outcomes:
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 1
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 2
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 3
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 4
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 5
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 6
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 7
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 8
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 9
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 10
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 11
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 12
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 13
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 14
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 15
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 16
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 17
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 18
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 19
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 20
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 21
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 22
measure: Pharmacokinetics for (R)- and (S)- Warfarin, measured by maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC)
timeFrame: Pharmacokinetic (PK) sampling will be performed day 23
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 1
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 2
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 3
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 4
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 5
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 6
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 7
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 8
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 9
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 10
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 11
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 12
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 13
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 14
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 15
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 16
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 17
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 18
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 19
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 20
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 21
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 22
measure: Pharmacodynamics measured by maximum international normalised ratio ( INRmax)
timeFrame: International normalised ratio (INR) sampling will be performed day 23
Secondary outcomes:
measure: Pharmacokinetics for AZD9668 measured by Css,max
timeFrame: Range from day 9 to 23
measure: Pharmacokinetics for AZD9668 measured by tss,max
timeFrame: Range from day 9 to 23
measure: Pharmacokinetics for AZD9668 measured by Css,min
timeFrame: Range from day 9 to 23
measure: Pharmacokinetics for AZD9668 measured by CLss/F
timeFrame: Range from day 9 to 23
measure: Severity of Adverse Events as a Measure of Safety and Tolerability
timeFrame: Adverse events will be collected pre-dose, during treatment and at follow up
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: Adverse events will be collected pre-dose, during treatment and at follow up
measure: Pharmacokinetics for (R)- and (S)- Warfarin measured tmax.
timeFrame: Range from day 1 to 23
measure: Pharmacokinetics for (R)- and (S)- Warfarin measured t½.
timeFrame: Range from day 1 to 23
measure: Pharmacokinetics for (R)- and (S)- Warfarin measured CL/F.
timeFrame: Range from day 1 to 23
measure: Pharmacokinetics for (R)- and (S)- Warfarin measured Vz/F.
timeFrame: Range from day 1 to 23
Other outcomes:
Locations:
city: Linköping
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D
name: Christopher D O'Brien, MD, PhD
role: STUDY_DIRECTOR
affiliation: Berzelius Clinical Reseach Centre
name: Ingemar Bylesjö, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Quintiles AB, Phase 1 Services
name: Wolfgang Kühn, MD
role: PRINCIPAL_INVESTIGATOR
References: