Open Label Study, Assessing the Effect of Diltiazem or Ketoconazole on the Pharmacokinetics of AZD9742 in Healthy Volunteers

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT01124760

Collaborator

(none)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to examine the effect of coadministration of CYP3A4 inhibitors on the pharmacokinetics of AZD9742.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics	Drug: AZD9742 Drug: Diltiazem Drug: ketoconazole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Single Center, Open Label, 2-consecutive-group, 2-period, 1-sequence Crossover Study to Assess the Effect of Diltiazem (Cardizem), a Moderate CYP3A4 Inhibitor, or Ketoconazole, a Potent CYP3A4 Inhibitor, on the Pharmacokinetics of a Single Intravenous Dose of 150mg of AZD9742.

Study Start Date :

May 1, 2010

Actual Primary Completion Date :

Jul 1, 2010

Actual Study Completion Date :

Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 AZD9742	Drug: AZD9742 Sterile solution, 620 mg (20 mg/mL) in 50 mL vial with a fill volume of 31 mL; On Day 7, a single 150 mg IV dose, coadministered after the morning dose of ketoconazole Drug: Diltiazem Orally, daily beginning on Day 4 for 14 consecutive days Other Names: Myoderm Drug: ketoconazole 200 mg, orally, every 12 hours starting on Day 4 for 10 consecutive days in which on Day 13 only the morning dose will be administered

Arm

Intervention/Treatment

Experimental: 1

AZD9742

Drug: AZD9742

Sterile solution, 620 mg (20 mg/mL) in 50 mL vial with a fill volume of 31 mL; On Day 7, a single 150 mg IV dose, coadministered after the morning dose of ketoconazole

Drug: Diltiazem

Orally, daily beginning on Day 4 for 14 consecutive days

Other Names:

Myoderm

Drug: ketoconazole

200 mg, orally, every 12 hours starting on Day 4 for 10 consecutive days in which on Day 13 only the morning dose will be administered

Outcome Measures

Primary Outcome Measures

Determine the effect of coadministration of CYP3A4 inhibitors (diltiazem and ketoconazole) on the pharmacokinetics of AZD9742 in blood and urine. [For diltiazem group - up to 18 days of pre-defined study days for pk profiling. For keoconazole - up to 14 days of pre-defined study days for pk profiling.]

Secondary Outcome Measures

Safety variables (adverse events, vital signs, physical examinations, clinical laboratory assessments, 12-lead ECG, telemetry) [Collected prior to treatment, during treatment, and follow-up for a maximum of 57 days for group 1 and 53 days for group 2 (this includes up to 28 days for screening).]

Eligibility Criteria

Criteria

Ages Eligible for Study:

23 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

non-childbearing potential, with suitable veins for cannulation or repeated venipuncture
Females must have a negative pregnancy test at screening and on admission to the unit, must not be lactating and must be of non-childbearing potential, confirmed at screening.
Male volunteers should be willing to use barrier contraception, ie, condoms, from the day of dosing until 3 months after dosing with the investigational product.

Exclusion Criteria:

History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the volunteer at risk because of participation in the study, or influence the results or the volunteer's ability to participate
History or presence of GI, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs as judged by Investigator.
Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product