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

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.

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

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: AZD9742; Drug: Diltiazem; Drug: ketoconazole

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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).

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Ralph Schutz, MD, Quintiles, Inc.; Study Director: Colleen Jensen, AstraZeneca

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: May 13, 2010
• First Submitted That Met QC Criteria: May 14, 2010
• First Posted (Estimate): May 17, 2010

Study Record Updates

• Last Update Posted (Estimate): August 3, 2010
• Last Update Submitted That Met QC Criteria: August 2, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: open label; 2-consecutive-group; 2-period; 1-sequence crossover study
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Membrane Transport Modulators; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Calcium-Regulating Hormones and Agents; Antifungal Agents; Steroid Synthesis Inhibitors; Calcium Channel Blockers; 14-alpha Demethylase Inhibitors; Ketoconazole; Diltiazem
• Other Study ID Numbers: D2690C00008