To Evaluate the Effect of AZD3199 on the Electrical Activity in the Heart

A Single-centre, Randomised, Double-blind, Double-dummy, Placebo Controlled, 4-way Crossover Phase I Study to Investigate the Effect of 2 Single Doses (400 μg and 1200 µg) of Inhaled AZD3199 on QT/QTc Interval, Compared to Placebo, Using Moxifloxacin (Avelox®) as a Positive Control, in Healthy Male Volunteers

The purpose of this research study is to evaluate the effect of AZD3199 on the electrical activity of the heart. The effect of AZD3199 will be compared to a licensed antibiotic (moxifloxacin). Moxifloxacin effects on the electrical activity of the heart are well known. Safety and tolerability of AZD3199 and how much AZD3199 enters the blood circulation will also be assessed.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease; Lung Disease
• Intervention / Treatment: Drug: AZD3199; Drug: Moxifloxacin; Other: Placebo comparator

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • UK
    • London, UK, United Kingdom
      • Research Site

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:

• Healthy male subjects aged 18 to 45 years (inclusive)
• Have a body mass index (BMI) between 19 and 30 kg/m2 and a body weight between 60 and 100 kg.
• Be a non-smoker or ex-smoker who has stopped smoking (or using other nicotine products) for >6 months prior to study start.
• Be able to inhale from the Turbuhaler inhaler according to given instructions.

Exclusion Criteria:

• Any clinically significant disease or disorder
• Any clinically relevant abnormal findings at screening examination
• History of additional risk factors for Torsade de Pointes (eg, heart failure, hypokalaemia, or family history of long QT syndrome).
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 400 µg AZD3199 + moxifloxacin placebo	Drug: AZD3199; Single dose, oral inhalation
Experimental: 2; 1200 µg AZD3199 + moxifloxacin placebo	Drug: AZD3199; Single dose, oral inhalation
Active Comparator: 3; AZD3199 placebo + moxifloxacin 400 mg	Drug: Moxifloxacin; Single dose, oral encapsulated tablet; Other Names: Avelox®
Placebo Comparator: 4; AZD3199 placebo + moxifloxacin placebo	Other: Placebo comparator; Single dose, oral inhalation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the effect of AZD3199 on the QT interval	QTcF or QTcI (algorithm based decision)	Throughout the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To investigate the effect of AZD3199 on additional electrocardiogram variables	QTcF or QTcI dependent on variable confirmed as primary; Holter-Bin QT	Throughout the study
To assess the pharmacokinetics of single doses of AZD3199.	AUC(0-24); Cmax; tmax	Throughout the study
To evaluate the safety and tolerability of single doses of AZD3199.	Adverse events - type of events and number of subjects experiencing adverse events.; Laboratory safety assessments, pulse, blood pressure and electrocardiogram interpretation - Summarised using descriptive stats. Judged regarding high/low values or changes from pre-dose.	Throughout the study

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Carin Jorup, MD, AstraZeneca R&D, Lund, Sweden; Principal Investigator: Leonard Siew, MB CHB, Quintiles Drug Research Unit at Guy's Hospital, London

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: October 12, 2010
• First Submitted That Met QC Criteria: October 15, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Estimate): February 16, 2011
• Last Update Submitted That Met QC Criteria: February 15, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Emphysema; Respiratory disease; Bronchiolitis; Lung disease causing persistent narrowing of the airways
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Adrenergic Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Moxifloxacin; AZD-3199
• Other Study ID Numbers: D0570C00004