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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Chronic Obstructive Pulmonary Disease, Lung Disease

Intervention / Treatment
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* Drug: AZD3199
* Drug: Moxifloxacin
* Other: Placebo comparator


Participation Criteria
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Eligibility Criteria
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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.

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: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory disease, Bronchiolitis, Emphysema, Lung disease causing persistent narrowing of the airways