Clinical trial NCT01480739: AZD5069 Neutrophil Function Study
Official title: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chemokine Receptor 2 (CXCR2) Antagonist
Keywords: Phase 1, AZD5069, safety and tolerability, healthy volunteer,
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2011-11-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in status of Neutrophil function (phagocytosis and oxidative burst) in subjects on AZD5069 and placebo
timeFrame: Day -1, Day 1, Day 2, Day 3, Day 4 and 7 days after end of treatment.
measure: Circulating neutrophils during exercise challenge measured by average neutrophil values over time
timeFrame: Pre-dose, 10 min, 2h, 4 hours post exercise test
measure: Circulating neutrophils following subcutaneous injection of granulocyte-colony stimulating factor (G-CSF)
timeFrame: Pre-dose, 2h, 6h, 12h, 24h, 36 hours post subcutaneous G-CSF
Secondary outcomes:
measure: Adverse events
timeFrame: Screening to Day 63
measure: Steady state 24 hour pharmacokinetic profile of the AZD5069 capsule following twice daily (bid) dosing
timeFrame: 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
measure: Steady state 24 hour profile of circulating neutrophils following twice daily dosing of AZD5069 and its relationship to plasma concentration
timeFrame: Pre-dose and 1, 2, 3, 5, 8, 12 hours post each dose on Days 1 - 4, Day 6 and Day 7
measure: Changes in baseline of vital signs (blood pressure and pulse), clinical laboratory tests, ECGs, and physical examination findings will be presented
timeFrame: Screening to Day 63
Other outcomes:
Locations:
city: London
country: United Kingdom
state: UK
Study officials:
affiliation: Quintiles research Unit
name: Tim Mant, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca Medical Science Director
name: Bengt Larsson, MD
role: STUDY_DIRECTOR
References:
citation: 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.