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

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

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

Study Overview

• Status: Completed
• Conditions: Bioavailability and AUC
• Intervention / Treatment: Drug: AZD5423; Drug: AZD5423; Drug: AZD5423; Drug: AZD5423; Drug: AZD5423; Drug: AZD5423

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • London, UK, United Kingdom

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; AZD5423 iv	Drug: AZD5423; solution for injection, administered as intravenous infusion Corr to total dose of 250 µg AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via Spira, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via I-neb, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension to be administered orally, corr to a total dose of 1200 µg AZD5423; Drug: AZD5423; dry powder inhaled via Turbuhaler, corr to approximately 200 µg lung deposited dose AZD5423; Drug: AZD5423; dry powder inhaled via New Dry Powder Inhaler, corr to approximately 200 µg lung deposited dose AZD5423
Experimental: 2; AZD5423 inhalation, Spira	Drug: AZD5423; solution for injection, administered as intravenous infusion Corr to total dose of 250 µg AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via Spira, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via I-neb, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension to be administered orally, corr to a total dose of 1200 µg AZD5423; Drug: AZD5423; dry powder inhaled via Turbuhaler, corr to approximately 200 µg lung deposited dose AZD5423; Drug: AZD5423; dry powder inhaled via New Dry Powder Inhaler, corr to approximately 200 µg lung deposited dose AZD5423
Experimental: 3; AZD5423 inhalation I-neb	Drug: AZD5423; solution for injection, administered as intravenous infusion Corr to total dose of 250 µg AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via Spira, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via I-neb, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension to be administered orally, corr to a total dose of 1200 µg AZD5423; Drug: AZD5423; dry powder inhaled via Turbuhaler, corr to approximately 200 µg lung deposited dose AZD5423; Drug: AZD5423; dry powder inhaled via New Dry Powder Inhaler, corr to approximately 200 µg lung deposited dose AZD5423
Experimental: 4; AZD5423 oral	Drug: AZD5423; solution for injection, administered as intravenous infusion Corr to total dose of 250 µg AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via Spira, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via I-neb, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension to be administered orally, corr to a total dose of 1200 µg AZD5423; Drug: AZD5423; dry powder inhaled via Turbuhaler, corr to approximately 200 µg lung deposited dose AZD5423; Drug: AZD5423; dry powder inhaled via New Dry Powder Inhaler, corr to approximately 200 µg lung deposited dose AZD5423
Experimental: 5; AZD5423 inhalation Turbuhaler	Drug: AZD5423; solution for injection, administered as intravenous infusion Corr to total dose of 250 µg AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via Spira, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via I-neb, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension to be administered orally, corr to a total dose of 1200 µg AZD5423; Drug: AZD5423; dry powder inhaled via Turbuhaler, corr to approximately 200 µg lung deposited dose AZD5423; Drug: AZD5423; dry powder inhaled via New Dry Powder Inhaler, corr to approximately 200 µg lung deposited dose AZD5423
Experimental: 6; AZD5423, New Dry Powder Inhaler	Drug: AZD5423; solution for injection, administered as intravenous infusion Corr to total dose of 250 µg AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via Spira, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension, inhaled via I-neb, corr to approximately 300 µg lung deposited dose AZD5423; Drug: AZD5423; nebuliser suspension to be administered orally, corr to a total dose of 1200 µg AZD5423; Drug: AZD5423; dry powder inhaled via Turbuhaler, corr to approximately 200 µg lung deposited dose AZD5423; Drug: AZD5423; dry powder inhaled via New Dry Powder Inhaler, corr to approximately 200 µg lung deposited dose AZD5423

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Carin Jorup, MD, AstraZeneca R&D, Molndal Sweden

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: July 5, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 10, 2012

Study Record Updates

• Last Update Posted (Estimate): January 14, 2015
• Last Update Submitted That Met QC Criteria: January 13, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Keywords: Phase I, Healthy male volunteers, pharmacokinetics
• Other Study ID Numbers: D2340C00012; Eudract 2012-002307-17