Phase I Study to Assess the Effect on Healthy Male Volunteers of Ketoconazole on the Pharmacokinetics of a Single Dose of AZD5069 Administered Orally. - Full Text View

Purpose

The main purpose of the study is to compare the change of the AZD5069 Pharmacokinetic profile when administered with ketoconazole. Subjects will be treated first with AZD5069 only followed by a washout period before starting with the combined treatment (both ketoconazole and AZD5069).

Condition	Intervention	Phase
Asthma, Pharmacokinetics, Cmax, Tmax, λz, AUC, Ketoconazole, Metabolite	Drug: AZD5069 Drug: Ketoconazole	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Basic Science
Official Title:	An Open-label, Fixed-sequence, Single-centre Phase I Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of AZD5069 After Oral Administration of a Single Dose AZD5069 to Healthy Male Volunteers

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Ketoconazole

U.S. FDA Resources

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

Pharmacokinetics of AZD5069 (15 mg) and a metabolite (AZ13587715) measured by AUC, AUC(0-t), Cmax, λz, t½λz, tmax, CL/F (AZD5069 only), Vz/F (alone and in combination with Ketoconazole) [ Time Frame: Day 1, Day 2 at 24 hours post dose and Day 3 at 48 hours post dose in period 1 and Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2. ] [ Designated as safety issue: No ]
(AUC(0-t)) area under the plasma concentration-time curve from time zero to time of last quantifiable concentration, (Cmax) observed maximum plasma concentration, (λz) terminal rate constant, (t½λz) terminal half-life, (tmax) time to reach maximum plasma concentration (tmax), (CL/F) apparent oral clearance (AZD5069 only), (Vz/F) apparent volume of distribution.
Pharmacokinetics of Ketoconazole measured by AUC(0-t) and Cmax (in combination with AZD5069) [ Time Frame: Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Numbers of circulating neutrophil in blood measured by AZD5069 administration alone and in combination with Ketoconazole [ Time Frame: Day 1, 2, 3 at predose, 4, 8, 12, 24, 48 hours post dose in period 1 and Day 1, 2, 3, 4 at predose, 4, 8, 12, 24, 48 hours post dose ] [ Designated as safety issue: Yes ]
Safety of AZD5069 (15 mg) in combination with Ketoconazole by assessing a panel of adverse events measures: laboratory assessments, vital signs, physical examination and 12-led electrocardiogram. [ Time Frame: Up to 2 months ] [ Designated as safety issue: Yes ]
Measures: laboratory assessments (clinical chemistry, haematology, urinalysis), vital signs (blood pressure, pulse rate, including body temperature), physical examination and 12-led electrocardiogram.

Enrollment:	15
Study Start Date:	December 2012
Study Completion Date:	February 2013
Primary Completion Date:	February 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: First AZD5069, then Ketoconazole + AZD5069 AZD5069 in first period (on 1 day) and in second period (after wash out) ketoconazole alone (on 2 days) then ketoconazole + AZD5069 (on 1 day), then again ketoconazole alone (on 2 days)	Drug: AZD5069 AZD5069 15 mg (3x5 mg capsules) single administration Drug: Ketoconazole Ketoconazole 400 mg (2x200 mg tablets)

Detailed Description:

An open-label, fixed-sequence, single-centre phase I study to assess the effect of ketoconazole on the pharmacokinetics of AZD5069 after oral administration of a single dose AZD5069 to healthy male volunteers

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Healthy male volunteers aged 18 to 50 years (inclusive).
Veins suitable for cannulation or repeated venipuncture.
Healthy volunteers with neutrophil counts within the laboratory normal reference range at Screening
Body mass index (BMI) ≥18.0 and ≤30.0 kg/m2 calculated from height and weight at screening; minimum weight 50 kg and maximum weight 100 kg.
Non-smokers or ex-smokers with no smoking history for the last 3 months prior to screening and a smoking history of less than 10 pack years (1 pack year = tobacco consumption corresponding to 20 cigarettes smoked per day for 1 year) at screening.

Exclusion Criteria:

Healthy volunteers with latent tuberculosis as suggested by their history and judged by the Investigator
Healthy volunteers who belong to a high-risk group for HIV infection.
Known or suspected history of significant drug abuse as judged by the Investigator.
History of alcohol abuse or excessive intake of alcohol as judged by the Investigator.
Plasma donation within 1 month of screening or any blood donation/blood loss >500 mL during the 3 months and/or 1350 mL within the 12 months prior to screening.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01735240

Locations

United Kingdom

London, United Kingdom

Sponsors and Collaborators

AstraZeneca

Investigators

Study Director:	Bengt Larsson, Dr.	AstraZeneca Pharmaceutical
Study Chair:	Gillian Pilbrow	AstraZeneca Pharmaceutical
Principal Investigator:	Leonard Siew, DR.	Quintiles Drug Research Unit at Guy's Hospital

More Information

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT01735240 History of Changes
Other Study ID Numbers:	D3550C00011
Study First Received:	November 20, 2012
Last Updated:	February 18, 2013
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by AstraZeneca:

Phase I,
healthy volunteers,
fixed-sequence,
open-label,

ketoconazole,
combination,
safety

Additional relevant MeSH terms:

Ketoconazole
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on June 17, 2013