Single-dose Crossover Study to Investigate Pharmacodynamics of AZD3199

Phase 2

Completed

Conditions: Asthma
Airway Obstruction

Interventions: Drug: AZD3199
Drug: Formoterol
Drug: Placebo

Registration Number: NCT00736489

Lead Sponsor: AstraZeneca

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
crossover dose 2	AZD3199	AZD3199 480 microgram
crossover dose 1	AZD3199	AZD3199 120 microgram
crossover dose 3	AZD3199	AZD3199 1920 microgram
crossover dose 6	Formoterol	Formoterol 36 microgram
crossover dose 4	Placebo	Placebo
crossover dose 5	Formoterol	Formoterol 9 microgram

Primary Outcome Measures

Name	Time	Method
S-potassium, Peak Effect Over 0 - 4 h Post-dose	0, 15min, 30min,1h, 2h, 4h	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.
FEV1 Peak Effect Within 0 - 24 h Post-dose	0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h	Maximum FEV1 value
E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit.	22- 26 h post dose	Residual FEV1 24 h post-dose
S-potassium, Average Effect Over 0 - 4 h Post-dose	0, 15min, 30min,1h, 2h, 4h	Average S-potassium concentration

Secondary Outcome Measures

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