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

Purpose

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

Condition	Intervention	Phase
Pharmacokinetics	Drug: AZD9742 Drug: Diltiazem Drug: ketoconazole	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Crossover Assignment Masking: 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.

Resource links provided by NLM:

Drug Information available for: Verapamil hydrochloride Diltiazem hydrochloride Diltiazem Ketoconazole Diltiazem malate

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Determine the effect of coadministration of CYP3A4 inhibitors (diltiazem and ketoconazole) on the pharmacokinetics of AZD9742 in blood and urine. [ Time Frame: 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. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Safety variables (adverse events, vital signs, physical examinations, clinical laboratory assessments, 12-lead ECG, telemetry) [ Time Frame: 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). ] [ Designated as safety issue: Yes ]

Enrollment:	28
Study Start Date:	May 2010
Study Completion Date:	July 2010
Primary Completion Date:	July 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 Name: 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

Arms

Assigned Interventions

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 Name: 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

Eligibility

Ages Eligible for Study:	23 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01124760

Locations

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

Sponsors and Collaborators

AstraZeneca

Investigators

Principal Investigator:	Ralph Schutz, MD	Quintiles
Study Director:	Colleen Jensen	AstraZeneca
Study Chair:	Brendan Smyth	AstraZeneca

More Information

No publications provided

Responsible Party:	MSD, AstraZeneca
ClinicalTrials.gov Identifier:	NCT01124760 History of Changes
Other Study ID Numbers:	D2690C00008
Study First Received:	May 13, 2010
Last Updated:	August 2, 2010
Health Authority:	United States: Food and Drug Administration

Keywords provided by AstraZeneca:

open label
2-consecutive-group
2-period
1-sequence crossover study

Additional relevant MeSH terms:

Diltiazem
Verapamil
Ketoconazole
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cardiovascular Agents

Therapeutic Uses
Antihypertensive Agents
Vasodilator Agents
Anti-Arrhythmia Agents
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 16, 2013