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

Phase 1

Completed

• Conditions: Asthma,; Pharmacokinetics,; λz,; Metabolite; Cmax,; Ketoconazole,; AUC,; Tmax,
• Interventions: Drug: AZD5069; Drug: Ketoconazole

• Registration Number: NCT01735240
• Lead Sponsor: AstraZeneca

Brief Summary

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).

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

Study Timeline

• Study First Submitted: 2012-11-20
• Study First Submitted QC: 2012-11-26
• Study First Posted: 2012-11-28
• Study Start: 2012-12
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-24
• Last Update Posted: 2015-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
First AZD5069, then Ketoconazole + AZD5069	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)
First AZD5069, then Ketoconazole + AZD5069	Ketoconazole	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)

Primary Outcome Measures

Name	Time	Method
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)	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.	(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)	Day 1, 2, 3 at 48 hours post dose and Day 4 at 72 post dose in period 2.

Secondary Outcome Measures

Name	Time	Method
Numbers of circulating neutrophil in blood measured by AZD5069 administration alone and in combination with Ketoconazole	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
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.	Up to 2 months	Measures: laboratory assessments (clinical chemistry, haematology, urinalysis), vital signs (blood pressure, pulse rate, including body temperature), physical examination and 12-led electrocardiogram.