Assess Safety, Tolerability and PK of AZD3199 in Japanese

Study Overview
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Brief Summary
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The primary objective of the study is to investigate the safety and tolerability of single and multiple once daily ascending doses of AZD3199 delivered as dry powder via the Turbuhaler inhaler in healthy male Japanese subjects by assessment of incidence and nature of adverse events (AEs), clinically significant abnormalities in ECG parameters, blood pressure (BP), pulse rate, lung function parameters, body temperature and laboratory variables (clinical chemistry, haematology and urinalysis). The secondary objectives of the study are to investigate the pharmacokinetics (PK) of single and multiple ascending doses of AZD3199 by assessment of the degree of accumulation, dose proportionality and time linearity in healthy Japanese subjects, and to investigate systemic β 2- adrenoreceptor mediated effects of single and multiple ascending doses of AZD3199 by assessment of potassium and lactate concentrations, tremor and palpitations, heart rate, QTc, pulse rate, blood pressure and FEV1.

Official Title
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A Phase I, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Single-Centre Study to Investigate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of AZD3199 Given Once Daily as Inhaled Formulation Via Turbuhaler to Japanese Healthy Men

Conditions
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Healthy

Intervention / Treatment
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* Drug: AZD3199 Turbuhaler®
* Drug: Placebo Turbuhaler®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be healthy Japanese volunteers, both of the volunteer's parents, and all grandparents must be Japanese. The volunteer must have been born in Japan, have a valid Japanese passport and must not have lived outside Japan for for more than 5 years. BMI 18 - 27, Weight 50 - 85 kg Be non-smoker or ex-smoker who has stopped smoking (or using other nicotine products) for >6 months prior to study start. Clinical normal physical findings Exclusion Criteria: Any clinically significant disease or disorder Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, ECG or lung function at baseline Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG that may interfere with the interpretation of QTc interval changes. Use of any medication (including OTC), herbal preparations, vitamins or nutritional supplements within 2 weeks prior to Visit 2, except for occasional intake of paracetamol (maximum daily dose of 4 g)

Ages Eligible for Study
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Minimum Age: 20 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Dry powder for oral inhalation | Drug: AZD3199 Turbuhaler®<br>* 240, 720 and 2160 μ g, single and multiple (o.d. for 12 days)<br>|
| Placebo Comparator: 2<br>Dry powder for oral inhalation | Drug: Placebo Turbuhaler®<br>* single and multiple (o.d. for 12 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety/Tolerability - adverse events (AEs), clinically significant abnormalities in ECG parameters, blood pressure (BP), pulse rate, lung function parameters, body temperature and laboratory variables (clinical chemistry, haematology and urinalysis) |  | During the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters derived from plasma concentration and optionally urinary excretion of AZD3199. |  | During residential period | 
| Pharmacodynamic Potassium and lactate concentrations, tremor and palpitations, heart rate, QTc, pulse rate, blood pressure, and forced expiratory volume in one second (FEV1). |  | During residential period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PK, AZD3199, Japanese Healthy Volunteers, Phase I study, Single and Multiple Ascending Dose, safety, tolerability