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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy; Asthma
• Intervention / Treatment: Drug: AZD5423; Drug: AZD5423; Drug: AZD5423; Drug: AZD5423

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; AZD5423 iv	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; solution for injection, administered as intravenous infusion Corr to total dose of 250µg AZD5423
Experimental: 2; AZD5423 inhalation, Spira	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; solution for injection, administered as intravenous infusion Corr to total dose of 250µg AZD5423
Experimental: 3; AZD5423 inhalation I-neb	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; solution for injection, administered as intravenous infusion Corr to total dose of 250µg AZD5423
Experimental: 4; AZD5423 oral	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; solution for injection, administered as intravenous infusion Corr to total dose of 250µg AZD5423

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Darren Wilbraham, Dr, Quintiles Drug Research Unit at Guy's Hospital

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: February 17, 2011
• First Submitted That Met QC Criteria: March 7, 2011
• First Posted (Estimate): March 8, 2011

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: pharmacokinetics; Healthy male volunteers; Phase I; mild asthmatics; Bioavailability and AUC; Level of AZD5423 in your blood
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D2340C00008