AZD5069 Neutrophil Function Study

A Randomised, Double-blind, Placebo-Controlled, Two-way Cross-over, Single Centre Study in Healthy Subjects to Assess the Effect of Oral Dosing of AZD5069 on Neutrophil Number and Function in Peripheral Blood and the Ability to Recruit Neutrophils Into the Circulation After Exercise and Subcutaneous

Study in healthy volunteer to see effect of AZD5069 and placebo on neutrophil number and function (phagocytosis and oxidative burst) in the circulation, following a burst of strenuous exercise and following subcutaneous injection of granulocyte-colony stimulating factor (G-CSF)

Study Overview

• Status: Completed
• Conditions: Chemokine Receptor 2 (CXCR2) Antagonist
• Intervention / Treatment: Drug: 100 mg (50 mg x 2) AZD5069; Drug: 100 mg Placebo

Detailed Description

A Randomised, Double-blind, Placebo-Controlled, Two-way Cross-over, Single Centre Study in Healthy Subjects to Assess the Effect of Oral Dosing of AZD5069 on Neutrophil Number and Function in Peripheral Blood and the Ability to Recruit Neutrophils into the Circulation after Exercise and Subcutaneous

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • London, UK, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy Caucasian male or post-menopausal/surgical sterile females, aged 18 to 45 years inclusive at screening
• Only women of non-childbearing potential are included in the study, ie, women who are permanently or surgically sterilised or post-menopausal
• Non-smokers or ex-smokers with no smoking history the last 12 months prior to Visit 1 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
• Body mass index (BMI) >18 kg/m2 and ≤30 kg/m2 and a minimum weight of 50 kg

Exclusion Criteria:

• Subjects with a history of or active or latent tuberculosis (TB), or close contact with anybody with active TB
• Subjects with a history of malignancy or neoplastic disease (except successfully treated basal or squamous cell carcinoma of the skin)
• Subjects who are pyrexial with a body temperature of greater than 37.7 C at Visit 2, or as judged by the Investigator
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) level ≥1.5 x upper limit of normal (ULN) at screening (Visit 2)
• Peripheral blood neutrophils above or below the laboratory reference range at screening (Visit 2) hsCRP above the upper limit of the laboratory reference range at Visit 2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; AZD5069 100 mg capsules (50 mg BD) for 7 days	Drug: 100 mg (50 mg x 2) AZD5069; Twice daily for 7 days
Experimental: 2; Placebo twice daily for 7 days	Drug: 100 mg Placebo; Twice daily for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in status of Neutrophil function (phagocytosis and oxidative burst) in subjects on AZD5069 and placebo	Day -1, Day 1, Day 2, Day 3, Day 4 and 7 days after end of treatment.
Circulating neutrophils during exercise challenge measured by average neutrophil values over time	Pre-dose, 10 min, 2h, 4 hours post exercise test
Circulating neutrophils following subcutaneous injection of granulocyte-colony stimulating factor (G-CSF)	Pre-dose, 2h, 6h, 12h, 24h, 36 hours post subcutaneous G-CSF

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events	Screening to Day 63
Steady state 24 hour pharmacokinetic profile of the AZD5069 capsule following twice daily (bid) dosing	Pre-dose on Days 1 - 4 On Day 3 with sampling pre-dose and at 1h, 2h, 3h, 5h, 8h, and 12 hours post dose
Steady state 24 hour profile of circulating neutrophils following twice daily dosing of AZD5069 and its relationship to plasma concentration	Pre-dose and 1, 2, 3, 5, 8, 12 hours post each dose on Days 1 - 4, Day 6 and Day 7
Changes in baseline of vital signs (blood pressure and pulse), clinical laboratory tests, ECGs, and physical examination findings will be presented	Screening to Day 63

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Tim Mant, MD, Quintiles research Unit; Study Director: Bengt Larsson, MD, AstraZeneca Medical Science Director

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, 2011
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: November 24, 2011
• First Submitted That Met QC Criteria: November 24, 2011
• First Posted (Estimate): November 29, 2011

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: Phase 1, AZD5069, safety and tolerability, healthy volunteer,
• Other Study ID Numbers: D3550C00017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No