Airway Obstruction, Asthma
Conditions
Keywords
Asthma, airway obstruction, beta2-agonist, efficacy, inhalation
Brief summary
The purpose of this study is to investigate the pharmacodynamics of single doses of AZD3199 in asthmatic patients.
Interventions
DRUGFormoterol
Dry powder for inhalation, single dose
DRUGAZD3199
Dry powder for inhalation, single dose
DRUGPlacebo
Dry powder for inhalation, single dose
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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, 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. |
| S-potassium, Average Effect Over 0 - 4 h Post-dose | 0, 15min, 30min,1h, 2h, 4h | Average S-potassium concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 0, 30min, 2h, 4h | Maximum SBP value over 4 h |
| QTcB, Average Effect Over 0 - 4 h Post-dose | 0, 30min, 2h, 4h | Average QTc Bazett over 4 h |
| Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 0, 30min, 2h, 4h | Average SBP value over 4 h |
| Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 0, 30min, 2h, 4h | Minimum DBP 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 |
| Heart Rate, Peak Effect Over 0 - 4 h Post-dose | 0, 30min, 2h, 4h | Maximum heart rate over 4 h |
| FEV1 Effect at 5 Min Post-dose | 5min | FEV1 at 5 minutes |
| QTcB, Peak Effect Over 0 - 4 h Post-dose | 0, 30min, 2h, 4h | Maximum 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. |
| 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 |
| 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 |
| 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 |
| Heart Rate, Average Effect Over 0 - 4 h Post-dose | 0, 30min, 2h, 4h | Average heart rate 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 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 |
Countries
Denmark, Sweden
Participant flow
Recruitment details
The study has been performed in Sweden and Denmark at two University hospital clinics and two CROs. The recruitment period was between 11 August 2008 to 22 October 2008.
Participants by arm
| Arm | Count |
|---|---|
| Baseline Total Total number of patients randomized and treated in the study | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Period 1 | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Baseline Total |
|---|---|
| Age, Continuous | 40.3 years |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 36 | 3 / 35 | 10 / 35 | 2 / 35 | 4 / 35 | 6 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 35 | 0 / 36 |
Outcome results
Primary
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
Time frame: 22- 26 h post dose
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. | 3.31 L | Standard Deviation 0.96 |
| AZD3199 480 mcg | E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. | 3.35 L | Standard Deviation 0.93 |
| AZD3199 1920 mcg | E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. | 3.40 L | Standard Deviation 0.94 |
| Formoterol 9 mcg | E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. | 3.26 L | Standard Deviation 0.94 |
| Formoterol 36 mcg | E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. | 3.36 L | Standard Deviation 0.97 |
| Placebo | E22-26: the Average of the FEV1 Value Between 22 and 26 h Post Dose for Every Treatment Visit. | 3.23 L | Standard Deviation 0.96 |
Primary
FEV1 Peak Effect Within 0 - 24 h Post-dose
Maximum FEV1 value
Time frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | FEV1 Peak Effect Within 0 - 24 h Post-dose | 3.56 L | Standard Deviation 0.94 |
| AZD3199 480 mcg | FEV1 Peak Effect Within 0 - 24 h Post-dose | 3.62 L | Standard Deviation 0.94 |
| AZD3199 1920 mcg | FEV1 Peak Effect Within 0 - 24 h Post-dose | 3.70 L | Standard Deviation 1.02 |
| Formoterol 9 mcg | FEV1 Peak Effect Within 0 - 24 h Post-dose | 3.62 L | Standard Deviation 1.01 |
| Formoterol 36 mcg | FEV1 Peak Effect Within 0 - 24 h Post-dose | 3.69 L | Standard Deviation 0.97 |
| Placebo | FEV1 Peak Effect Within 0 - 24 h Post-dose | 3.44 L | Standard Deviation 0.99 |
Primary
S-potassium, Average Effect Over 0 - 4 h Post-dose
Average S-potassium concentration
Time frame: 0, 15min, 30min,1h, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. Two patients on AZD3199 1920 mcg had data not sufficient for computing PD parameters and for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | S-potassium, Average Effect Over 0 - 4 h Post-dose | 4.22 mmol/L | Standard Deviation 0.19 |
| AZD3199 480 mcg | S-potassium, Average Effect Over 0 - 4 h Post-dose | 4.21 mmol/L | Standard Deviation 0.26 |
| AZD3199 1920 mcg | S-potassium, Average Effect Over 0 - 4 h Post-dose | 4.17 mmol/L | Standard Deviation 0.26 |
| Formoterol 9 mcg | S-potassium, Average Effect Over 0 - 4 h Post-dose | 4.19 mmol/L | Standard Deviation 0.2 |
| Formoterol 36 mcg | S-potassium, Average Effect Over 0 - 4 h Post-dose | 3.99 mmol/L | Standard Deviation 0.17 |
| Placebo | S-potassium, Average Effect Over 0 - 4 h Post-dose | 4.21 mmol/L | Standard Deviation 0.25 |
Primary
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.
Time frame: 0, 15min, 30min,1h, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. Two patients on AZD3199 1920 mcg had data not sufficient for computing PD parameters and for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | S-potassium, Peak Effect Over 0 - 4 h Post-dose | 4.04 mmol/L | Standard Deviation 0.19 |
| AZD3199 480 mcg | S-potassium, Peak Effect Over 0 - 4 h Post-dose | 4.03 mmol/L | Standard Deviation 0.25 |
| AZD3199 1920 mcg | S-potassium, Peak Effect Over 0 - 4 h Post-dose | 3.98 mmol/L | Standard Deviation 0.28 |
| Formoterol 9 mcg | S-potassium, Peak Effect Over 0 - 4 h Post-dose | 4.04 mmol/L | Standard Deviation 0.2 |
| Formoterol 36 mcg | S-potassium, Peak Effect Over 0 - 4 h Post-dose | 3.84 mmol/L | Standard Deviation 0.21 |
| Placebo | S-potassium, Peak Effect Over 0 - 4 h Post-dose | 4.04 mmol/L | Standard Deviation 0.23 |
Secondary
Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose
Average DBP value over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 71.4 mmHg | Standard Deviation 10 |
| AZD3199 480 mcg | Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 72.0 mmHg | Standard Deviation 8.9 |
| AZD3199 1920 mcg | Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 71.6 mmHg | Standard Deviation 9.5 |
| Formoterol 9 mcg | Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 71.5 mmHg | Standard Deviation 9.2 |
| Formoterol 36 mcg | Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 71.0 mmHg | Standard Deviation 8.6 |
| Placebo | Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 72.7 mmHg | Standard Deviation 8.4 |
Secondary
Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose
Minimum DBP value over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 67.3 mmHg | Standard Deviation 10.3 |
| AZD3199 480 mcg | Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 67.6 mmHg | Standard Deviation 7.9 |
| AZD3199 1920 mcg | Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 66.7 mmHg | Standard Deviation 9.6 |
| Formoterol 9 mcg | Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 66.9 mmHg | Standard Deviation 9.1 |
| Formoterol 36 mcg | Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 66.7 mmHg | Standard Deviation 9.6 |
| Placebo | Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 68.8 mmHg | Standard Deviation 8 |
Secondary
FEV1 Average Effect Over 0 - 12 h Post-dose
FEV1 average effect over 12 h day-time period
Time frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | FEV1 Average Effect Over 0 - 12 h Post-dose | 3.33 L | Standard Deviation 0.92 |
| AZD3199 480 mcg | FEV1 Average Effect Over 0 - 12 h Post-dose | 3.40 L | Standard Deviation 0.89 |
| AZD3199 1920 mcg | FEV1 Average Effect Over 0 - 12 h Post-dose | 3.48 L | Standard Deviation 0.97 |
| Formoterol 9 mcg | FEV1 Average Effect Over 0 - 12 h Post-dose | 3.40 L | Standard Deviation 0.98 |
| Formoterol 36 mcg | FEV1 Average Effect Over 0 - 12 h Post-dose | 3.51 L | Standard Deviation 0.95 |
| Placebo | FEV1 Average Effect Over 0 - 12 h Post-dose | 3.20 L | Standard Deviation 0.96 |
Secondary
FEV1 Average Effect Over 0 - 24 h Post-dose
FEV1 average effect over 24 h dosing interval
Time frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | FEV1 Average Effect Over 0 - 24 h Post-dose | 3.31 L | Standard Deviation 0.93 |
| AZD3199 480 mcg | FEV1 Average Effect Over 0 - 24 h Post-dose | 3.36 L | Standard Deviation 0.91 |
| AZD3199 1920 mcg | FEV1 Average Effect Over 0 - 24 h Post-dose | 3.44 L | Standard Deviation 0.95 |
| Formoterol 9 mcg | FEV1 Average Effect Over 0 - 24 h Post-dose | 3.35 L | Standard Deviation 0.98 |
| Formoterol 36 mcg | FEV1 Average Effect Over 0 - 24 h Post-dose | 3.46 L | Standard Deviation 0.96 |
| Placebo | FEV1 Average Effect Over 0 - 24 h Post-dose | 3.19 L | Standard Deviation 0.95 |
Secondary
FEV1 Average Effect Over 12 - 24 h Post-dose
FEV1 average effect over 12 h night-time period
Time frame: 12h, 14h, 18h, 22h, 24h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo treatment had data not sufficient for computing PD parameters and for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | FEV1 Average Effect Over 12 - 24 h Post-dose | 3.28 L | Standard Deviation 0.95 |
| AZD3199 480 mcg | FEV1 Average Effect Over 12 - 24 h Post-dose | 3.33 L | Standard Deviation 0.92 |
| AZD3199 1920 mcg | FEV1 Average Effect Over 12 - 24 h Post-dose | 3.41 L | Standard Deviation 0.94 |
| Formoterol 9 mcg | FEV1 Average Effect Over 12 - 24 h Post-dose | 3.30 L | Standard Deviation 0.98 |
| Formoterol 36 mcg | FEV1 Average Effect Over 12 - 24 h Post-dose | 3.40 L | Standard Deviation 0.98 |
| Placebo | FEV1 Average Effect Over 12 - 24 h Post-dose | 3.19 L | Standard Deviation 0.95 |
Secondary
FEV1 Effect at 5 Min Post-dose
FEV1 at 5 minutes
Time frame: 5min
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. Two patients on Placebo and 1 on AZD3199 480 mcg had data not sufficient for computing PD parameters and for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | FEV1 Effect at 5 Min Post-dose | 3.36 L | Standard Deviation 0.88 |
| AZD3199 480 mcg | FEV1 Effect at 5 Min Post-dose | 3.38 L | Standard Deviation 0.92 |
| AZD3199 1920 mcg | FEV1 Effect at 5 Min Post-dose | 3.33 L | Standard Deviation 1.03 |
| Formoterol 9 mcg | FEV1 Effect at 5 Min Post-dose | 3.37 L | Standard Deviation 0.95 |
| Formoterol 36 mcg | FEV1 Effect at 5 Min Post-dose | 3.47 L | Standard Deviation 0.93 |
| Placebo | FEV1 Effect at 5 Min Post-dose | 3.13 L | Standard Deviation 0.86 |
Secondary
Heart Rate, Average Effect Over 0 - 4 h Post-dose
Average heart rate over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Heart Rate, Average Effect Over 0 - 4 h Post-dose | 58.3 bpm | Standard Deviation 7.9 |
| AZD3199 480 mcg | Heart Rate, Average Effect Over 0 - 4 h Post-dose | 59.0 bpm | Standard Deviation 8.5 |
| AZD3199 1920 mcg | Heart Rate, Average Effect Over 0 - 4 h Post-dose | 61.8 bpm | Standard Deviation 9 |
| Formoterol 9 mcg | Heart Rate, Average Effect Over 0 - 4 h Post-dose | 58.6 bpm | Standard Deviation 9.2 |
| Formoterol 36 mcg | Heart Rate, Average Effect Over 0 - 4 h Post-dose | 62.7 bpm | Standard Deviation 10 |
| Placebo | Heart Rate, Average Effect Over 0 - 4 h Post-dose | 58.1 bpm | Standard Deviation 8.6 |
Secondary
Heart Rate, Peak Effect Over 0 - 4 h Post-dose
Maximum heart rate over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Heart Rate, Peak Effect Over 0 - 4 h Post-dose | 64.0 bpm | Standard Deviation 8.8 |
| AZD3199 480 mcg | Heart Rate, Peak Effect Over 0 - 4 h Post-dose | 64.1 bpm | Standard Deviation 9.6 |
| AZD3199 1920 mcg | Heart Rate, Peak Effect Over 0 - 4 h Post-dose | 66.9 bpm | Standard Deviation 9.5 |
| Formoterol 9 mcg | Heart Rate, Peak Effect Over 0 - 4 h Post-dose | 63.8 bpm | Standard Deviation 10.2 |
| Formoterol 36 mcg | Heart Rate, Peak Effect Over 0 - 4 h Post-dose | 66.8 bpm | Standard Deviation 10.9 |
| Placebo | Heart Rate, Peak Effect Over 0 - 4 h Post-dose | 64.5 bpm | Standard Deviation 11.3 |
Secondary
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
Time frame: 0, 15min, 30min, 1h, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo, 1 patient on formoterol 36 mcg and 1 patient on AZD3199 480 mcg had no data for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Palpitations, Average Effect Over 0 - 4 h Post-dose | 0.00 Score on a scale | Standard Deviation 0.02 |
| AZD3199 480 mcg | Palpitations, Average Effect Over 0 - 4 h Post-dose | 0.01 Score on a scale | Standard Deviation 0.05 |
| AZD3199 1920 mcg | Palpitations, Average Effect Over 0 - 4 h Post-dose | 0.02 Score on a scale | Standard Deviation 0.08 |
| Formoterol 9 mcg | Palpitations, Average Effect Over 0 - 4 h Post-dose | 0.00 Score on a scale | Standard Deviation 0 |
| Formoterol 36 mcg | Palpitations, Average Effect Over 0 - 4 h Post-dose | 0.11 Score on a scale | Standard Deviation 0.33 |
| Placebo | Palpitations, Average Effect Over 0 - 4 h Post-dose | 0.00 Score on a scale | Standard Deviation 0 |
Secondary
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
Time frame: 0, 15min, 30min, 1h, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo, 1 patient on formoterol 36 mcg and 1 patient on AZD3199 480 mcg had no data for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Palpitations, Peak Effect Over 0 - 4 h Post-dose | 0.03 Score on a scale | Standard Deviation 0.17 |
| AZD3199 480 mcg | Palpitations, Peak Effect Over 0 - 4 h Post-dose | 0.03 Score on a scale | Standard Deviation 0.17 |
| AZD3199 1920 mcg | Palpitations, Peak Effect Over 0 - 4 h Post-dose | 0.09 Score on a scale | Standard Deviation 0.37 |
| Formoterol 9 mcg | Palpitations, Peak Effect Over 0 - 4 h Post-dose | 0.00 Score on a scale | Standard Deviation 0 |
| Formoterol 36 mcg | Palpitations, Peak Effect Over 0 - 4 h Post-dose | 0.18 Score on a scale | Standard Deviation 0.52 |
| Placebo | Palpitations, Peak Effect Over 0 - 4 h Post-dose | 0.00 Score on a scale | Standard Deviation 0 |
Secondary
Plasma AZD3199 AUC0-24
Area under the plasma concentration curve from time 0 to 24 h post-dose
Time frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacokinetic analysis set.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3199 120 mcg | Plasma AZD3199 AUC0-24 | 1.83 nmol*h/L |
| AZD3199 480 mcg | Plasma AZD3199 AUC0-24 | 9.75 nmol*h/L |
| AZD3199 1920 mcg | Plasma AZD3199 AUC0-24 | 46.06 nmol*h/L |
Secondary
Plasma AZD3199 Cmax
Maximum plasma concentration of AZD3199 measured
Time frame: 0, 5min, 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacokinetic analysis set.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| AZD3199 120 mcg | Plasma AZD3199 Cmax | 0.99 nmol/L |
| AZD3199 480 mcg | Plasma AZD3199 Cmax | 5.39 nmol/L |
| AZD3199 1920 mcg | Plasma AZD3199 Cmax | 24.55 nmol/L |
Secondary
Pulse, Average Effect Over 0 - 4 h Post-dose
Average pulse over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Pulse, Average Effect Over 0 - 4 h Post-dose | 57.1 bpm | Standard Deviation 8 |
| AZD3199 480 mcg | Pulse, Average Effect Over 0 - 4 h Post-dose | 59.0 bpm | Standard Deviation 8.7 |
| AZD3199 1920 mcg | Pulse, Average Effect Over 0 - 4 h Post-dose | 61.9 bpm | Standard Deviation 9.1 |
| Formoterol 9 mcg | Pulse, Average Effect Over 0 - 4 h Post-dose | 58.6 bpm | Standard Deviation 9.4 |
| Formoterol 36 mcg | Pulse, Average Effect Over 0 - 4 h Post-dose | 62.8 bpm | Standard Deviation 10.1 |
| Placebo | Pulse, Average Effect Over 0 - 4 h Post-dose | 58.8 bpm | Standard Deviation 8.8 |
Secondary
Pulse, Peak Effect Over 0 - 4 h Post-dose
Maximum pulse over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Pulse, Peak Effect Over 0 - 4 h Post-dose | 62.1 bpm | Standard Deviation 9.4 |
| AZD3199 480 mcg | Pulse, Peak Effect Over 0 - 4 h Post-dose | 65.0 bpm | Standard Deviation 11 |
| AZD3199 1920 mcg | Pulse, Peak Effect Over 0 - 4 h Post-dose | 66.7 bpm | Standard Deviation 9.9 |
| Formoterol 9 mcg | Pulse, Peak Effect Over 0 - 4 h Post-dose | 63.6 bpm | Standard Deviation 11 |
| Formoterol 36 mcg | Pulse, Peak Effect Over 0 - 4 h Post-dose | 67.3 bpm | Standard Deviation 11.6 |
| Placebo | Pulse, Peak Effect Over 0 - 4 h Post-dose | 65.3 bpm | Standard Deviation 10.4 |
Secondary
QTcB, Average Effect Over 0 - 4 h Post-dose
Average QTc Bazett over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | QTcB, Average Effect Over 0 - 4 h Post-dose | 398 ms | Standard Deviation 19.9 |
| AZD3199 480 mcg | QTcB, Average Effect Over 0 - 4 h Post-dose | 397 ms | Standard Deviation 22.3 |
| AZD3199 1920 mcg | QTcB, Average Effect Over 0 - 4 h Post-dose | 402 ms | Standard Deviation 21.2 |
| Formoterol 9 mcg | QTcB, Average Effect Over 0 - 4 h Post-dose | 395 ms | Standard Deviation 21.4 |
| Formoterol 36 mcg | QTcB, Average Effect Over 0 - 4 h Post-dose | 406 ms | Standard Deviation 24.4 |
| Placebo | QTcB, Average Effect Over 0 - 4 h Post-dose | 395 ms | Standard Deviation 19.8 |
Secondary
QTcB, Peak Effect Over 0 - 4 h Post-dose
Maximum QTc Bazett over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | QTcB, Peak Effect Over 0 - 4 h Post-dose | 412 ms | Standard Deviation 21.6 |
| AZD3199 480 mcg | QTcB, Peak Effect Over 0 - 4 h Post-dose | 407 ms | Standard Deviation 22.8 |
| AZD3199 1920 mcg | QTcB, Peak Effect Over 0 - 4 h Post-dose | 413 ms | Standard Deviation 22 |
| Formoterol 9 mcg | QTcB, Peak Effect Over 0 - 4 h Post-dose | 408 ms | Standard Deviation 21.6 |
| Formoterol 36 mcg | QTcB, Peak Effect Over 0 - 4 h Post-dose | 415 ms | Standard Deviation 24.6 |
| Placebo | QTcB, Peak Effect Over 0 - 4 h Post-dose | 408 ms | Standard Deviation 20.8 |
Secondary
Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose
Average SBP value over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 121.1 mmHg | Standard Deviation 13.7 |
| AZD3199 480 mcg | Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 121.8 mmHg | Standard Deviation 11.8 |
| AZD3199 1920 mcg | Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 121.3 mmHg | Standard Deviation 11.9 |
| Formoterol 9 mcg | Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 120.9 mmHg | Standard Deviation 12.8 |
| Formoterol 36 mcg | Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 122.6 mmHg | Standard Deviation 11.8 |
| Placebo | Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose | 121.3 mmHg | Standard Deviation 13.5 |
Secondary
Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose
Maximum SBP value over 4 h
Time frame: 0, 30min, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 126.8 mmHg | Standard Deviation 14.5 |
| AZD3199 480 mcg | Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 128.3 mmHg | Standard Deviation 13.4 |
| AZD3199 1920 mcg | Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 127.4 mmHg | Standard Deviation 12 |
| Formoterol 9 mcg | Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 127.3 mmHg | Standard Deviation 13.2 |
| Formoterol 36 mcg | Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 129.9 mmHg | Standard Deviation 12.1 |
| Placebo | Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose | 126.4 mmHg | Standard Deviation 14.4 |
Secondary
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.
Time frame: 0, 15min, 30min, 1h, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo, 1 patient on formoterol 36 mcg and 1 patient on AZD3199 480 mcg had no data for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Tremor, Average Effect Over 0 - 4 h Post-dose | 0.00 Score on a scale | Standard Deviation 0.02 |
| AZD3199 480 mcg | Tremor, Average Effect Over 0 - 4 h Post-dose | 0.02 Score on a scale | Standard Deviation 0.08 |
| AZD3199 1920 mcg | Tremor, Average Effect Over 0 - 4 h Post-dose | 0.04 Score on a scale | Standard Deviation 0.11 |
| Formoterol 9 mcg | Tremor, Average Effect Over 0 - 4 h Post-dose | 0.05 Score on a scale | Standard Deviation 0.18 |
| Formoterol 36 mcg | Tremor, Average Effect Over 0 - 4 h Post-dose | 0.16 Score on a scale | Standard Deviation 0.34 |
| Placebo | Tremor, Average Effect Over 0 - 4 h Post-dose | 0.01 Score on a scale | Standard Deviation 0.06 |
Secondary
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.
Time frame: 0, 15min, 30min, 1h, 2h, 4h
Population: Two patients discontinued after the first treatment period and were excluded from pharmacodynamic analysis set since these patients are non-informative regarding treatment differences. One patient on Placebo, 1 patient on formoterol 36 mcg and 1 patient on AZD3199 480 mcg had no data for subsequent analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZD3199 120 mcg | Tremor, Peak Effect Over 0 - 4 h Post-dose | 0.06 Score on a scale | Standard Deviation 0.24 |
| AZD3199 480 mcg | Tremor, Peak Effect Over 0 - 4 h Post-dose | 0.06 Score on a scale | Standard Deviation 0.24 |
| AZD3199 1920 mcg | Tremor, Peak Effect Over 0 - 4 h Post-dose | 0.17 Score on a scale | Standard Deviation 0.45 |
| Formoterol 9 mcg | Tremor, Peak Effect Over 0 - 4 h Post-dose | 0.11 Score on a scale | Standard Deviation 0.32 |
| Formoterol 36 mcg | Tremor, Peak Effect Over 0 - 4 h Post-dose | 0.47 Score on a scale | Standard Deviation 0.66 |
| Placebo | Tremor, Peak Effect Over 0 - 4 h Post-dose | 0.03 Score on a scale | Standard Deviation 0.17 |