A Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Multiple Ascending Doses of AZD5069 in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to explore the safety and tolerability of AZD5069 at steady-state, following twice a day oral dosing in healthy subjects. AZD5069 is being developed by AstraZeneca and this study is being carried out on behalf of the sponsor by Quintiles Drug Research Unit at Guy's Hospital, London. This is the second time that AZD5069 will be administered to humans in clinical trials. We are conducting this study to determine whether AZD5069 is safe and well tolerated by healthy males and females at different dose levels over an 8-day dosing period. We will also be studying how quickly AZD5069 is absorbed into and cleared by the body. It is planned that there will be up to 3 dose groups in the study and each group will consist of up to 12 volunteers, with 9 receiving the active drug and 3 receiving placebo. The study involves 3 visits over approximately 8 weeks, and will include 1 residential visit lasting 10 nights and a follow up.

Official Title
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A Phase I, Single Centre, Double-blind, Randomised, Placebo-controlled, Parallel-group Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Oral AZD5069 After Administration of Multiple Ascending Doses for 8 Days in Healthy Male or Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: AZD5069
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated, written informed consent Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg Healthy male or female (of non child bearing potential)volunteers with suitable veins for cannulation or repeated venepuncture Exclusion Criteria: Subjects must not have any clinically significant disease or disorder, which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results, or the subjects ability to participate Subjects must not have any history of gastrointestinal, liver or kidney disease, or any other condition known to interfere with how drugs are absorbed, used or eliminated by the body Subjects must not have had any significant illness or medical/surgical procedures or injuries with 4 weeks of administration of the investigational product

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: AZD5069<br>* oral suspension dose of AZD5069. Multiple doses will be given once daily on day 1 and day 8 and twice daily on days 2 to 7<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* oral suspension dose of matched placebo. Multiple doses will be given once daily on day 1 and day 8 and twice daily on days 2 to 7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, electrocardiograms (ECGs), laboratory variables, blood pressure, pulse rate, body temperature, QT interval and continuous cardiac monitoring using telemetry |  | Baselines assessments at Visit 1 (enrolment) or pre-dose on Day 1 with assessments during Visit 2 at protocol defined time-points post-dose until 96hr post final dose. Follow up assessments at Visit 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile: concentration of AZD5069 in blood |  | Samples collected at Visit 2 from pre-dose and at regular protocol defined intervals up to 96 hours post-dose | 
| Assessment of ex vivo GROa stimulated CD11b expression on neutrophils in whole blood |  | Samples collected at Visit 2 from pre-dose and at regular protocol defined intervals up to 96 hours post-dose | 
| Measurement of the effect of AZD5069 on blood cells |  | Samples collected at Visit 2 from pre-dose and at regular protocol defined intervals up to 96 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, multiple ascending dose, Safety, Tolerability, Healthy Volunteer