AZD5069 Neutrophil Function Study

Phase 1

Completed

• Conditions: Chemokine Receptor 2 (CXCR2) Antagonist
• Interventions: Drug: 100 mg (50 mg x 2) AZD5069; Drug: 100 mg Placebo

• Registration Number: NCT01480739
• Lead Sponsor: AstraZeneca

Brief Summary

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)

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 Timeline

• Study First Submitted: 2011-11-24
• Study First Submitted QC: 2011-11-24
• Study First Posted: 2011-11-29
• Study Start: 2011-12
• Primary Completion: 2012-07
• Study Completion: 2012-07
• Status Verified: 2015-06
• Last Update Submitted: 2015-06-24
• Last Update Posted: 2015-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
1	100 mg (50 mg x 2) AZD5069	AZD5069 100 mg capsules (50 mg BD) for 7 days
2	100 mg Placebo	Placebo twice daily for 7 days

Primary Outcome Measures

Name	Time	Method
Circulating neutrophils during exercise challenge measured by average neutrophil values over time	Pre-dose, 10 min, 2h, 4 hours post exercise test
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 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

Name	Time	Method
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