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

Pharmacokinetics Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01214122
• Other study ID #: D0520C00013
• Secondary ID: 2010-022360-12
• Status: Withdrawn
• Phase: Phase 1
• First received: September 21, 2010
• Last updated: January 28, 2013
• Start date: November 2010
• Est. completion date: December 2010

Study information

• Verified date: January 2013
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2010
• Est. primary completion date: December 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Pharmacodynamics
• Pharmacokinetics

Intervention

Drug:
• AZD9668
60 mg orally twice daily for 11 days
• Warfarin
10 x 2.5 (25) mg orally once daily on day 1 and on day 14

Locations

Country	Name	City	State
Sweden	Research Site	Linköping
Sweden	Research Site	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 1	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 2	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 3	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 4	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 5	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 6	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 7	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 8	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 9	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 10	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 11	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 12	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 13	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 14	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 15	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 16	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 17	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 18	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 19	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 20	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 21	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 22	No
Primary	Pharmacodynamics measured by maximum international normalised ratio ( INRmax)		International normalised ratio (INR) sampling will be performed day 23	No
Secondary	Pharmacokinetics for AZD9668 measured by Css,max		Range from day 9 to 23	No
Secondary	Pharmacokinetics for AZD9668 measured by tss,max		Range from day 9 to 23	No
Secondary	Pharmacokinetics for AZD9668 measured by Css,min		Range from day 9 to 23	No
Secondary	Pharmacokinetics for AZD9668 measured by CLss/F		Range from day 9 to 23	No
Secondary	Severity of Adverse Events as a Measure of Safety and Tolerability		Adverse events will be collected pre-dose, during treatment and at follow up	Yes
Secondary	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	Yes
Secondary	Pharmacokinetics for (R)- and (S)- Warfarin measured tmax.		Range from day 1 to 23	No
Secondary	Pharmacokinetics for (R)- and (S)- Warfarin measured t½.		Range from day 1 to 23	No
Secondary	Pharmacokinetics for (R)- and (S)- Warfarin measured CL/F.		Range from day 1 to 23	No
Secondary	Pharmacokinetics for (R)- and (S)- Warfarin measured Vz/F.		Range from day 1 to 23	No