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

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

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).

Study Overview

• Status: Completed
• Conditions: Asthma,; Pharmacokinetics,; Cmax,; Tmax,; λz,; AUC,; Ketoconazole,; Metabolite
• Intervention / Treatment: Drug: AZD5069; Drug: Ketoconazole

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 Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	(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.	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.
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

Outcome Measure	Measure Description	Time Frame
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.	Measures: laboratory assessments (clinical chemistry, haematology, urinalysis), vital signs (blood pressure, pulse rate, including body temperature), physical examination and 12-led electrocardiogram.	Up to 2 months

Collaborators and Investigators

• Sponsor: 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

Publications and helpful links

General Publications

• Cullberg M, Arfvidsson C, Larsson B, Malmgren A, Mitchell P, Wahlby Hamren U, Wray H. Pharmacokinetics of the Oral Selective CXCR2 Antagonist AZD5069: A Summary of Eight Phase I Studies in Healthy Volunteers. Drugs R D. 2018 Jun;18(2):149-159. doi: 10.1007/s40268-018-0236-x.

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: November 26, 2012
• First Posted (Estimate): November 28, 2012

Study Record Updates

• Last Update Posted (Estimate): June 25, 2015
• Last Update Submitted That Met QC Criteria: June 24, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: safety; Phase I,; healthy volunteers,; ketoconazole,; open-label,; combination,; fixed-sequence,
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Ketoconazole
• Other Study ID Numbers: D3550C00011