AZD5069 Neutrophil Function Study

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Chemokine Receptor 2 (CXCR2) Antagonist

Intervention / Treatment
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* Drug: 100 mg (50 mg x 2) AZD5069
* Drug: 100 mg Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD5069 100 mg capsules (50 mg BD) for 7 days | Drug: 100 mg (50 mg x 2) AZD5069<br>* Twice daily for 7 days<br>|
| Experimental: 2<br>Placebo twice daily for 7 days | Drug: 100 mg Placebo<br>* Twice daily for 7 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1, AZD5069, safety and tolerability, healthy volunteer,