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

Study Overview
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Brief Summary
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The purpose of this study is to look at drug levels of AZD5423 in blood when the drug is administered in different ways - orally, intravenously or inhaled (with four different devices), to healthy subjects

Detailed Description
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A Phase I, Single Centre, Open, Partly Randomised, Crossover Study in Healthy Subjects to Evaluate AZD5423 Absolute Pulmonary Bioavailability when Administered Inhaled via a New Dry Powder Inhaler, Turbuhaler, Spira nebulizer and I-neb AAD system

Official Title
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A Phase I, Single Centre, Open, Partly Randomised, Crossover Study in Healthy Subjects to Evaluate AZD5423 Absolute Pulmonary Bioavailability When Administered Inhaled Via a New Dry Powder Inhaler, Turbuhaler, Spira Nebulizer and I-neb AAD System

Conditions
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Bioavailability and AUC

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or women of non-childbearing potential aged 18-45 years inclusive with suitable veins for cannulation or repeated vein puncture Have a body mass index (BMI) between 19 and 30 kg/m2 (inclusive and rounding allowed) and weight between 50 and 100 kg (inclusive) Be able to inhale from the inhaler devices used in the study according to given instructions as well as be able to perform spirometry Exclusion Criteria: History of any clinically significant disease or disorder Current smokers Any clinically relevant abnormal findings

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 250 µg 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>|
| Experimental: 5<br>AZD5423 inhalation Turbuhaler | Drug: AZD5423<br>* dry powder inhaled via Turbuhaler, corr to approximately 200 µg lung deposited dose AZD5423<br>|
| Experimental: 6<br>AZD5423, New Dry Powder Inhaler | Drug: AZD5423<br>* dry powder inhaled via New Dry Powder Inhaler, corr to approximately 200 µg lung deposited dose AZD5423<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of AZD5423 delivered by the new dry powder inhaler in terms of: Fpulmonary |  | Blood samples taken pre-dose and at10, 20 and 40 minutes and 1, 1.5, 2, 4, 6, 8, 12,16, 24, 36, 48 and 96 hours post dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of AZD5423 following i.v administration in terms of : AUC, AUC(0-t), Fpo, Finhalation total, Fpulmonary, Foral, Frel, Frel Cmax, Cmax, Cmax(tmax), t½λz, MAT, MRT, Vz and Vss |  | Blood samples taken pre-dose and at 5, 10, 25, 30, 35 and 45 minutes and 1, 1.5, 2, 4, 6, 8, 12,16, 24, 36, 48, 72 and 96 hours post dose. | 
| Pharmacokinetics of AZD5423 following oral administration in terms of : AUC, AUC(0-t), Fpo, Finhalation total, Fpulmonary, Foral, Frel, Frel Cmax, Cmax, Cmax(tmax), t½λz, MAT, MRT, Vz and Vss |  | Blood samples taken pre-dose and at10, 20 and 40 minutes and 1, 1.5, 2, 4, 6, 8, 12,16, 24, 36 and 48 hours post dose. | 
| Pharmacokinetics of AZD5423 following oral inhalation by Spira, I-neb, Turbuhaler and New Dry Powder Inhaler in terms of : AUC, AUC(0-t), Fpo, Finhalation total, Fpulmonary, Foral, Frel, Frel Cmax, Cmax, Cmax(tmax), t½λz, MAT, MRT, Vz and Vss |  | Blood samples taken pre-dose and at10, 20 and 40 minutes and 1, 1.5, 2, 4, 6, 8, 12,16, 24, 36, 48 and 96 hours post dose. | 
| Safety profile in terms of adverse events, ECG, heart rate, blood pressure, pulse rate, body temperature, physical examination, spirometry, haematology, clinical chemistry and urinalysis. | No formal statistical tests will be performed. | Screening to 28 days post dose. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Healthy male volunteers, pharmacokinetics