A Study in Healthy Subjects to Investigate Pharmacokinetics of AZD8683 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 AZD8683 in blood when the drug is administered in different ways - orally, intravenously or inhaled (with two different devices), to healthy subjects

Detailed Description
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A Phase I, Single-centre, Open-label, Partly Randomised, Cross-over Single Dose Study in Healthy Volunteers to Evaluate the Absolute Pulmonary Bioavailability of AZD8683 when Administered Inhaled via a New Dry Powder Inhaler and via Turbuhaler™

Official Title
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A Phase I, Single-centre, Open-label, Partly Randomised, Cross-over Single Dose Study in Healthy Volunteers to Evaluate the Absolute Pulmonary Bioavailability of AZD8683 When Administered Inhaled Via a New Dry Powder Inhaler and Via Turbuhaler™

Conditions
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Healthy

Intervention / Treatment
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* Drug: AZD8683
* Drug: AZD8683
* Drug: AZD8683
* Drug: AZD8683


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males 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 weight between 50 and 100 kg (inclusive) Be able to inhale from the inhaler devices used in the study. Exclusion Criteria: History of any clinically significant disease or disorder Current smokers Any clinically relevant abnormal findings in physical examination or laboratory values.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: 1<br>AZD8683 iv | Drug: AZD8683<br>* Solution for injection, administered as intravenous infusion Total dose of 100µg AZD8683<br>|
| Experimental: 2<br>AZD8683 oral | Drug: AZD8683<br>* Solution to be administered orally Total dose of 950 µg AZD8683<br>|
| Experimental: 3<br>AZD8683 inhalation New Dry Powder Inhaler | Drug: AZD8683<br>* Dry powder inhaled via New Dry Powder Inhaler, 540 µg delivered dose AZD8683<br>|
| Experimental: 4<br>AZD8683 inhalation Turbuhaler™ | Drug: AZD8683<br>* Dry powder inhaled via Turbuhaler™, 600 µg delivered dose AZD8683<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute pulmonary bioavailability of AZD8683 delivered by the new dry powder inhaler in terms of: Fpulmonary |  | Blood samples taken pre-dose and at 5, 15 and 30 minutes and 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute pulmonary bioavailability of AZD8683 delivered by the Turbuhaler™ in terms of: Fpulmonary |  | Blood samples taken pre-dose and at 5, 15 and 30 minutes and 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours post dose. | 
| Pharmacokinetics of AZD8683 following administration in terms of oral inhalation by Turbuhaler™ and New Dry Powder Inhaler in terms of: Finhalation total, FrelAUC, Frel Cmax and Foral |  | Blood samples taken pre-dose and at 5, 15 and 30 minutes and 1, 2, 4, 8, 12,24, 36, 48, 72, 96, 120 and 144 hours post dose. | 
| Pharmacokinetics of AZD8683 following oral administration in terms of: Fpo |  | Blood samples taken pre-dose and at 5, 15 and 30 minutes and 1, 2, 4, 8, 12 ,24, 36, and 48 hours post dose. | 
| Pharmacokinetics of AZD8683 following oral administration and oral inhalation by Turbuhaler™ and New Dry Powder inhaler in terms of : AUC, AUC(0-t), Cmax, tmax, t½λz, MRT and MAT. |  | Blood samples taken pre-dose and at 5, 15 and 30 minutes and 1, 2, 4, 8, 12,24, 36, 48, 72 96, 120 and 144 hours post dose. | 
| Pharmacokinetics of AZD8683 following i.v. administration in terms of: CL, Vz, and Vss |  | Blood samples taken pre-dose and at 5, 15, 20, 25 and 40 minutes and 1, 2, 4, 8, 12, 24, 48, 72, 96, 120 and 144 hours post dose. | 
| Safety profile in terms of adverse events, ECG, heart rate, blood pressure, body temperature, physical examination, spirometry, haematology, clinical chemistry and urinalysis. | No formal statistical tests will be performed. | Screening to 4 weeks after last dose. | 

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