Single-dose Crossover Study to Investigate Pharmacodynamics of AZD3199

Study Overview
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Brief Summary
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The purpose of this study is to investigate the pharmacodynamics of single doses of AZD3199 in asthmatic patients.

Official Title
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A Phase II, Double-blind, Placebo-controlled, Randomised, 6-way Cross-over, Single-dose Study to Investigate the Local and Systemic Effects of 3 Doses of Inhaled AZD3199 (a β2-agonist) Compared to Formoterol in Asthmatic Patients

Conditions
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Asthma, Airway Obstruction

Intervention / Treatment
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* Drug: AZD3199
* Drug: Formoterol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Asthmatic patients with pre-bronchodilatory FEV1 above 60% of predicted normal and above 1.5 liters. Men and post-menopausal women above 18 years of age. Reversible airway obstruction in response to classical beta2-agonist (salbutamol) Non/ex-smokers Exclusion Criteria: Any clinically significant disease or disorder other than asthma Any clinically relevant abnormal findings at screening examinations Treatment with systemic glucocorticosteroids within the past 30 days Inhaled corticosteroid use if dosing is not kept constant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: crossover dose 1<br>AZD3199 120 microgram | Drug: AZD3199<br>* Dry powder for inhalation, single dose<br>|
| Experimental: crossover dose 2<br>AZD3199 480 microgram | Drug: AZD3199<br>* Dry powder for inhalation, single dose<br>|
| Experimental: crossover dose 3<br>AZD3199 1920 microgram | Drug: AZD3199<br>* Dry powder for inhalation, single dose<br>|
| Placebo Comparator: crossover dose 4<br>Placebo | Drug: Placebo<br>* Dry powder for inhalation, single dose<br>|
| Active Comparator: crossover dose 5<br>Formoterol 9 microgram | Drug: Formoterol<br>* Dry powder for inhalation, single dose<br>* Other names: Oxis;|
| Active Comparator: crossover dose 6<br>Formoterol 36 microgram | Drug: Formoterol<br>* Dry powder for inhalation, single dose<br>* Other names: Oxis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 Peak Effect Within 0 - 24 h Post-dose | Maximum FEV1 value | 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h | 
| E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. | Residual FEV1 24 h post-dose | 22- 26 h post dose | 
| S-potassium, Peak Effect Over 0 - 4 h Post-dose | Minimum S-potassium concentration (A well-known effect of beta2-agonists (AZD3199 is a beta2-agonist) is a reduction in serum potassium levels. The minimum value has therefore been evaluated. | 0, 15min, 30min,1h, 2h, 4h | 
| S-potassium, Average Effect Over 0 - 4 h Post-dose | Average S-potassium concentration | 0, 15min, 30min,1h, 2h, 4h | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 Effect at 5 Min Post-dose | FEV1 at 5 minutes | 5min | 
| FEV1 Average Effect Over 0 - 24 h Post-dose | FEV1 average effect over 24 h dosing interval | 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h | 
| FEV1 Average Effect Over 0 - 12 h Post-dose | FEV1 average effect over 12 h day-time period | 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h | 
| FEV1 Average Effect Over 12 - 24 h Post-dose | FEV1 average effect over 12 h night-time period | 12h, 14h, 18h, 22h, 24h | 
| Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | Maximum SBP value over 4 h | 0, 30min, 2h, 4h | 
| Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | Average SBP value over 4 h | 0, 30min, 2h, 4h | 
| Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | Minimum DBP value over 4 h | 0, 30min, 2h, 4h | 
| Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | Average DBP value over 4 h | 0, 30min, 2h, 4h | 
| Pulse, Peak Effect Over 0 - 4 h Post-dose | Maximum pulse over 4 h | 0, 30min, 2h, 4h | 
| Pulse, Average Effect Over 0 - 4 h Post-dose | Average pulse over 4 h | 0, 30min, 2h, 4h | 
| Heart Rate, Peak Effect Over 0 - 4 h Post-dose | Maximum heart rate over 4 h | 0, 30min, 2h, 4h | 
| Heart Rate, Average Effect Over 0 - 4 h Post-dose | Average heart rate over 4 h | 0, 30min, 2h, 4h | 
| QTcB, Peak Effect Over 0 - 4 h Post-dose | Maximum QTc Bazett over 4 h | 0, 30min, 2h, 4h | 
| QTcB, Average Effect Over 0 - 4 h Post-dose | Average QTc Bazett over 4 h | 0, 30min, 2h, 4h | 
| Tremor, Peak Effect Over 0 - 4 h Post-dose | Maximum tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h. | 0, 15min, 30min, 1h, 2h, 4h | 
| Tremor, Average Effect Over 0 - 4 h Post-dose | Average tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h. | 0, 15min, 30min, 1h, 2h, 4h | 
| Palpitations, Peak Effect Over 0 - 4 h Post-dose | Maximum palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h | 0, 15min, 30min, 1h, 2h, 4h | 
| Palpitations, Average Effect Over 0 - 4 h Post-dose | Average palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h | 0, 15min, 30min, 1h, 2h, 4h | 
| Plasma AZD3199 Cmax | Maximum plasma concentration of AZD3199 measured | 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h | 
| Plasma AZD3199 AUC0-24 | Area under the plasma concentration curve from time 0 to 24 h post-dose | 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, airway obstruction, beta2-agonist, efficacy, inhalation