A Study in Healthy Subjects and Mild Asthmatics to Investigate Pharmacokinetics of AZD5423 When Administered in Different Ways

Study Overview
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Brief Summary
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A study in healthy subjects and mild asthmatics to investigate Pharmacokinetics of AZD5423 when administered in different ways.

Official Title
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An Open, Partly Randomised, Four-way Cross-over Study in Healthy Subjects and in Patients With Mild Allergic Asthma to Investigate the Bioavailability and Basic Pharmacokinetics of a Single Dose of AZD5423 When Administered Intravenously, Orally, Inhaled Via SPIRA Nebuliser or Inhaled Via I-neb® AAD Systems

Conditions
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Healthy, Asthma

Intervention / Treatment
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* Drug: AZD5423
* Drug: AZD5423
* Drug: AZD5423
* Drug: AZD5423


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male healthy subjects and male asthma patients aged 18 to 45 years (inclusive) Have a body mass index (BMI) between 18 and 30 kg/m2 (inclusive and rounding allowed) and weight between 50 and 100 kg (inclusive) Be able to inhale from the SPIRA nebuliser and I-neb® according to the provided instructions Asthma patients should fulfil the following criteria: Pre-bronchodilator forced expiratory volume at 1 second (FEV1) ≥70% of predicted normal value Asthma diagnosis according to GINA guidelines with a history of episodic wheeze and shortness of breath Exclusion Criteria: History of any clinically significant disease or disorder Any clinically relevant abnormal findings Current smokers Asthma patients: Worsening of asthma or respiratory infection within 6 weeks before screening Asthma patients: Use of inhaled, nasal, oral, rectal or parenteral corticosteroids within 30 days before first administration of investigational product and during the study

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

Sexes Eligible for Study
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Male

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: 1<br>AZD5423 iv | Drug: AZD5423<br>* solution for injection, administered as intravenous infusion Corr to total dose of 250µg AZD5423<br>|
| Experimental: 2<br>AZD5423 inhalation, Spira | Drug: AZD5423<br>* nebuliser suspension, inhaled via Spira, corr to approximately 300 µg lung deposited dose AZD5423<br>|
| Experimental: 3<br>AZD5423 inhalation I-neb | Drug: AZD5423<br>* nebuliser suspension, inhaled via I-neb, corr to approximately 300 µg lung deposited dose AZD5423<br>|
| Experimental: 4<br>AZD5423 oral | Drug: AZD5423<br>* nebuliser suspension to be administered orally, corr to a total dose of 1200 µg AZD5423<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of AZD5423 measured by: Absolute bioavailability (F) |  | Pharmacokinetic (PK) sampling will be performed day 1 to day 5 for each treatment period | 
| Pharmacokinetics of AZD5423 measured by: Pulmonary bioavailability (Fpulmonary) |  | Pharmacokinetic (PK) sampling will be performed day 1 to day 5 for each treatment period | 
| Pharmacokinetics of AZD5423 measured by: Oral bioavailability after inhaled treatments (Foral) |  | Pharmacokinetic (PK) sampling will be performed day 1 to day 5 for each treatment period | 
| Pharmacokinetics of AZD5423 measured by: Area under the plasma concentration-time curve from time zero to infinity (AUC). |  | Pharmacokinetic (PK) sampling will be performed day 1 to day 5 for each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the pharmacokinetics between healthy subjects and asthma patients and estimate the basic pharmacokinetic parameters of AZD5423 by measuring e.g. maximum plasma concentration, Cmax |  | Pharmacokinetic (PK) sampling will be performed day 1 to day 5 for each treatment period | 
| To evaluate the safety and tolerability of AZD5423 measured by adverse events, laboratory variables, physical examination, electrocardiograms, blood pressure and pulse, and spirometry. | To evaluate the safety and tolerability of AZD5423 measured by (Adverse events) (Laboratory variables) (Physical examination) (Electrocardiograms) (blood pressure and pulse) (Spirometry) | From screening to follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Healthy male volunteers, mild asthmatics, pharmacokinetics, Bioavailability and AUC, Level of AZD5423 in your blood