Pharmacodynamics, Pharmacokinetics
Conditions
Keywords
Phase 1, Drug-Drug interaction, warfarin, AZD9668, resulting from AZD9668 and Warfarin interaction, pharmacokinetics, pharmacodynamics
Brief summary
The primary purpose of this study is to determine whether the treatment with AZD9668 will affect the metabolism and effect of Warfarin.
Interventions
DRUGAZD9668
60 mg orally twice daily for 11 days
DRUGWarfarin
10 x 2.5 (25) mg orally once daily on day 1 and on day 14
Sponsors
AstraZeneca
Study design
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| Pharmacodynamics measured by maximum international normalised ratio ( INRmax) | International normalised ratio (INR) sampling will be performed day 1 |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | Adverse events will be collected pre-dose, during treatment and at follow up |
| Pharmacokinetics for AZD9668 measured by Css,max | Range from day 9 to 23 |
| Pharmacokinetics for (R)- and (S)- Warfarin measured t½. | Range from day 1 to 23 |
| Pharmacokinetics for (R)- and (S)- Warfarin measured CL/F. | Range from day 1 to 23 |
| Pharmacokinetics for (R)- and (S)- Warfarin measured Vz/F. | Range from day 1 to 23 |
| Pharmacokinetics for (R)- and (S)- Warfarin measured tmax. | Range from day 1 to 23 |
| Pharmacokinetics for AZD9668 measured by tss,max | Range from day 9 to 23 |
Countries
Sweden
Outcome results
None listed