Study to Investigate Relative Bioavailability of up to Five Different Formulations of AZD5069

Study Overview
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Brief Summary
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Study to investigate relative bioavailability of up to five different formulations of AZD5069

Detailed Description
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An Open-label, Single Centre Relative Bioavailability Study With an Adaptive Design Comparing up to 5 Solid Oral AZD5069 Formulations After Single Dose Administration to Healthy Volunteers

Official Title
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An Open-label, Single Centre Relative Bioavailability Study With an Adaptive Design Comparing up to 5 Solid Oral AZD5069 Formulations After Single Dose Administration to Healthy Volunteers

Conditions
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Uncontrolled and Persistent Asthma

Intervention / Treatment
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* Drug: Phase IIb formulation
* Drug: Putative phase III formulation
* Drug: Slow dissolution variant 1
* Drug: Slow dissolution variant 2
* Drug: Test treatment E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and/or female volunteers aged 18 to 50 years (inclusive). Non-smokers or ex-smokers with no smoking history for the last 3 months prior to screening. Body mass index (BMI) ≥18.0 and ≤30.0 kg/m2 calculated from height and weight at screening; minimum (min) weight 50 kg and maximum (max) weight 100 kg. Healthy volunteers with neutrophil counts within the laboratory range at screening. - Exclusion Criteria: A definite or suspected personal history of severe allergy, intolerance or hypersensitivity or ongoing allergy to drugs with a similar chemical structure or class to AZD5069 and/or the excipients, as judged to be clinically relevant by the Investigator. Healthy volunteers who have previously received AZD5069. Volunteers with latent tuberculosis as suggested by their history and judged by the Investigator; confirmatory testing with eg, Quantiferon(R) -TB Gold may be done if required. Volunteers who have received live or live-attenuated vaccine in the 2 weeks prior to the first administration of the IP -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Phase IIb formulation | Drug: Phase IIb formulation<br>* Single oral dose 45mg AZD5069<br>|
| Experimental: Treatment B<br>Putative phase III formulation | Drug: Putative phase III formulation<br>* Single oral dose 45mg AZD5069<br>|
| Experimental: Treatment C<br>Slow dissolution variant 1 | Drug: Slow dissolution variant 1<br>* Single oral dose 45mg AZD5069<br>|
| Experimental: Treatment D<br>Slow dissolution variant 2 | Drug: Slow dissolution variant 2<br>* Single oral dose 45mg AZD 5069<br>|
| Experimental: Treatment E<br>Optional treatment that may use one of 3 45 mg (intermediate dissolution variant) of AZD5069 | Drug: Test treatment E<br>* Tablet formulation E, 45 mg (intermediate dissolution variant) of AZD5069<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of pharmacokinetics of AZD5069 and its metabolite in terms of area under plasma concentration-time curve from time zero to the time of last quantifiable analyte concentration and extrapolated to infinity (AUC(0-last) and AUC) | Curve taken during each of the 5 treatments | Samples taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose | 
| Description of pharmacokinetics of AZD5069 and its metabolite in terms of observed maximum plasma concentration (Cmax), plasma concentration measured at 12 hours (C12h), Cmax/C12h ratio, Cmax/AUC ratio, terminal rate constant (λz) | Curve taken during each of the 5 treatments | Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose | 
| Description of pharmacokinetics of AZD5069 and its metabolite in terms of terminal half-life (t½λz), time to reach maximum plasma concentration (tmax) | Curve taken during each of the 5 treatments | Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose | 
| Description of pharmacokinetics of AZD5069 and its metabolite in terms of apparent systemic clearance (CL/F) (AZD5069 only), and apparent volume of distribution (Vz/F) (AZD5069 only) | Curve taken during each of the 5 treatments | Sample taken predose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, and 24 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Description of effect on neutrophils in terms of circulating neutrophil numbers reported as absolute circulating neutrophil counts (ANC). The minimum absolute neutrophil count (ANCmin) and the time to ANCmin (ANCtmin) | Samples taken during each of the 5 treatments | Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| Description of effect on neutrophils in terms of mean of ANC values from predose to 24 hours postdose (ANCmean), the minimum of the ANC ratio values (ANCmin,ratio) | Samples taken during each of the 5 treatments | Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose | 
| Description of effect on neutrophils in terms of the mean of ANC ratio values calculated baseline to 24 hours post dose (ANCmean,ratio) | Samples taken during each of the 5 treatments | Baseline sample taken at predose day 1 and then 2, 4, 6, 8, 10, 12, and 24 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Relative bioavailability, Healthy volunteers, Neutrophils