Trial Outcomes & Findings for Single-dose Crossover Study to Investigate Pharmacodynamics of AZD3199 (NCT NCT00736489)

NCT ID: NCT00736489

Last Updated: 2014-05-19

Results Overview

Maximum FEV1 value

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 37 participants
• Primary outcome timeframe: 0, 5min, 15min, 30min, 1h, 2h, 4h, 6h, 8h, 10h, 12h, 14h, 18h, 22h, 24h
• Results posted on: 2014-05-19

Participant Flow

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.

Participant milestones

Measure	APCDEBa AZD3199 120 Mcg followed by Placebo followed by AZD3199 1920 Mcg followed by Formoterol 9 Mcg followed by Formoterol 36 Mcg followed by AZD3199 480 Mcg.	BADEPCa AZD3199 480 Mcg followed by AZD3199 120 Mcg followed by Formoterol 9 Mcg followed by Formoterol 36 Mcg followed by Placebo followed by AZD3199 1920 Mcg.	CBEPADa AZD3199 1920 Mcg followed by AZD3199 480 Mcg followed by Formoterol 36 Mcg followed by Placebo followed by AZD3199 120 Mcg followed by Formoterol 9 Mcg .	DCPABEa Formoterol 9 Mcg followed by AZD3199 1920 Mcg followed by Placebo followed by AZD3199 120 Mcg followed by AZD3199 480 Mcg followed by Formoterol 36 Mcg.	EDABCPa Formoterol 36 Mcg followed by Formoterol 9 Mcg followed by AZD3199 120 Mcg followed by AZD3199 480 Mcg followed by AZD3199 1920 Mcg followed by Placebo.	PEBCDAa Placebo followed by Formoterol 36 Mcg followed by AZD3199 480 Mcg followed by AZD3199 1920 Mcg followed by Formoterol 9 Mcg followed by AZD3199 120 Mcg.
Period 1 STARTED	6	5	6	7	7	6
Period 1 COMPLETED	5	5	6	7	7	5
Period 1 NOT COMPLETED	1	0	0	0	0	1
Period 2 STARTED	5	5	6	7	7	5
Period 2 COMPLETED	5	5	6	7	7	5
Period 2 NOT COMPLETED	0	0	0	0	0	0
Period 3 STARTED	5	5	6	7	7	5
Period 3 COMPLETED	5	5	6	7	7	5
Period 3 NOT COMPLETED	0	0	0	0	0	0
Period 4 STARTED	5	5	6	7	7	5
Period 4 COMPLETED	5	5	6	7	7	5
Period 4 NOT COMPLETED	0	0	0	0	0	0
Period 5 STARTED	5	5	6	7	7	5
Period 5 COMPLETED	5	5	6	7	7	5
Period 5 NOT COMPLETED	0	0	0	0	0	0
Period 6 STARTED	5	5	6	7	7	5
Period 6 COMPLETED	5	5	6	7	7	5
Period 6 NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Measure	APCDEBa AZD3199 120 Mcg followed by Placebo followed by AZD3199 1920 Mcg followed by Formoterol 9 Mcg followed by Formoterol 36 Mcg followed by AZD3199 480 Mcg.	BADEPCa AZD3199 480 Mcg followed by AZD3199 120 Mcg followed by Formoterol 9 Mcg followed by Formoterol 36 Mcg followed by Placebo followed by AZD3199 1920 Mcg.	CBEPADa AZD3199 1920 Mcg followed by AZD3199 480 Mcg followed by Formoterol 36 Mcg followed by Placebo followed by AZD3199 120 Mcg followed by Formoterol 9 Mcg .	DCPABEa Formoterol 9 Mcg followed by AZD3199 1920 Mcg followed by Placebo followed by AZD3199 120 Mcg followed by AZD3199 480 Mcg followed by Formoterol 36 Mcg.	EDABCPa Formoterol 36 Mcg followed by Formoterol 9 Mcg followed by AZD3199 120 Mcg followed by AZD3199 480 Mcg followed by AZD3199 1920 Mcg followed by Placebo.	PEBCDAa Placebo followed by Formoterol 36 Mcg followed by AZD3199 480 Mcg followed by AZD3199 1920 Mcg followed by Formoterol 9 Mcg followed by AZD3199 120 Mcg.
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

Single-dose Crossover Study to Investigate Pharmacodynamics of AZD3199

Baseline characteristics by cohort

Measure	Baseline Total n=37 Participants Total number of patients randomized and treated in the study
Age, Continuous	40.3 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Maximum FEV1 value

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
FEV1 Peak Effect Within 0 - 24 h Post-dose	3.56 L Standard Deviation 0.94	3.62 L Standard Deviation 0.94	3.70 L Standard Deviation 1.02	3.62 L Standard Deviation 1.01	3.69 L Standard Deviation 0.97	3.44 L Standard Deviation 0.99

PRIMARY outcome

Timeframe: 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.

Residual FEV1 24 h post-dose

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
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	3.35 L Standard Deviation 0.93	3.40 L Standard Deviation 0.94	3.26 L Standard Deviation 0.94	3.36 L Standard Deviation 0.97	3.23 L Standard Deviation 0.96

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=33 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
S-potassium, Peak Effect Over 0 - 4 h Post-dose	4.04 mmol/L Standard Deviation 0.19	4.03 mmol/L Standard Deviation 0.25	3.98 mmol/L Standard Deviation 0.28	4.04 mmol/L Standard Deviation 0.20	3.84 mmol/L Standard Deviation 0.21	4.04 mmol/L Standard Deviation 0.23

PRIMARY outcome

Timeframe: 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.

Average S-potassium concentration

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=33 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
S-potassium, Average Effect Over 0 - 4 h Post-dose	4.22 mmol/L Standard Deviation 0.19	4.21 mmol/L Standard Deviation 0.26	4.17 mmol/L Standard Deviation 0.26	4.19 mmol/L Standard Deviation 0.20	3.99 mmol/L Standard Deviation 0.17	4.21 mmol/L Standard Deviation 0.25

SECONDARY outcome

Timeframe: 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.

FEV1 at 5 minutes

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=34 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=33 Participants Placebo inhaled via Turbuhaler
FEV1 Effect at 5 Min Post-dose	3.36 L Standard Deviation 0.88	3.38 L Standard Deviation 0.92	3.33 L Standard Deviation 1.03	3.37 L Standard Deviation 0.95	3.47 L Standard Deviation 0.93	3.13 L Standard Deviation 0.86

SECONDARY outcome

Timeframe: 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.

FEV1 average effect over 24 h dosing interval

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
FEV1 Average Effect Over 0 - 24 h Post-dose	3.31 L Standard Deviation 0.93	3.36 L Standard Deviation 0.91	3.44 L Standard Deviation 0.95	3.35 L Standard Deviation 0.98	3.46 L Standard Deviation 0.96	3.19 L Standard Deviation 0.95

SECONDARY outcome

Timeframe: 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.

FEV1 average effect over 12 h day-time period

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
FEV1 Average Effect Over 0 - 12 h Post-dose	3.33 L Standard Deviation 0.92	3.40 L Standard Deviation 0.89	3.48 L Standard Deviation 0.97	3.40 L Standard Deviation 0.98	3.51 L Standard Deviation 0.95	3.20 L Standard Deviation 0.96

SECONDARY outcome

Timeframe: 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.

FEV1 average effect over 12 h night-time period

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
FEV1 Average Effect Over 12 - 24 h Post-dose	3.28 L Standard Deviation 0.95	3.33 L Standard Deviation 0.92	3.41 L Standard Deviation 0.94	3.30 L Standard Deviation 0.98	3.40 L Standard Deviation 0.98	3.19 L Standard Deviation 0.95

SECONDARY outcome

Timeframe: 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.

Maximum SBP value over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
Systolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose	126.8 mmHg Standard Deviation 14.5	128.3 mmHg Standard Deviation 13.4	127.4 mmHg Standard Deviation 12.0	127.3 mmHg Standard Deviation 13.2	129.9 mmHg Standard Deviation 12.1	126.4 mmHg Standard Deviation 14.4

SECONDARY outcome

Timeframe: 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.

Average SBP value over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
Systolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose	121.1 mmHg Standard Deviation 13.7	121.8 mmHg Standard Deviation 11.8	121.3 mmHg Standard Deviation 11.9	120.9 mmHg Standard Deviation 12.8	122.6 mmHg Standard Deviation 11.8	121.3 mmHg Standard Deviation 13.5

SECONDARY outcome

Timeframe: 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.

Minimum DBP value over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
Diastolic Blood Pressure, Peak Effect Over 0 - 4 h Post-dose	67.3 mmHg Standard Deviation 10.3	67.6 mmHg Standard Deviation 7.9	66.7 mmHg Standard Deviation 9.6	66.9 mmHg Standard Deviation 9.1	66.7 mmHg Standard Deviation 9.6	68.8 mmHg Standard Deviation 8.0

SECONDARY outcome

Timeframe: 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.

Average DBP value over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
Diastolic Blood Pressure, Average Effect Over 0 - 4 h Post-dose	71.4 mmHg Standard Deviation 10.0	72.0 mmHg Standard Deviation 8.9	71.6 mmHg Standard Deviation 9.5	71.5 mmHg Standard Deviation 9.2	71.0 mmHg Standard Deviation 8.6	72.7 mmHg Standard Deviation 8.4

SECONDARY outcome

Timeframe: 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.

Maximum pulse over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
Pulse, Peak Effect Over 0 - 4 h Post-dose	62.1 bpm Standard Deviation 9.4	65.0 bpm Standard Deviation 11.0	66.7 bpm Standard Deviation 9.9	63.6 bpm Standard Deviation 11.0	67.3 bpm Standard Deviation 11.6	65.3 bpm Standard Deviation 10.4

SECONDARY outcome

Timeframe: 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.

Average pulse over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
Pulse, Average Effect Over 0 - 4 h Post-dose	57.1 bpm Standard Deviation 8.0	59.0 bpm Standard Deviation 8.7	61.9 bpm Standard Deviation 9.1	58.6 bpm Standard Deviation 9.4	62.8 bpm Standard Deviation 10.1	58.8 bpm Standard Deviation 8.8

SECONDARY outcome

Timeframe: 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.

Maximum heart rate over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
Heart Rate, Peak Effect Over 0 - 4 h Post-dose	64.0 bpm Standard Deviation 8.8	64.1 bpm Standard Deviation 9.6	66.9 bpm Standard Deviation 9.5	63.8 bpm Standard Deviation 10.2	66.8 bpm Standard Deviation 10.9	64.5 bpm Standard Deviation 11.3

SECONDARY outcome

Timeframe: 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.

Average heart rate over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
Heart Rate, Average Effect Over 0 - 4 h Post-dose	58.3 bpm Standard Deviation 7.9	59.0 bpm Standard Deviation 8.5	61.8 bpm Standard Deviation 9.0	58.6 bpm Standard Deviation 9.2	62.7 bpm Standard Deviation 10.0	58.1 bpm Standard Deviation 8.6

SECONDARY outcome

Timeframe: 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.

Maximum QTc Bazett over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
QTcB, Peak Effect Over 0 - 4 h Post-dose	412 ms Standard Deviation 21.6	407 ms Standard Deviation 22.8	413 ms Standard Deviation 22.0	408 ms Standard Deviation 21.6	415 ms Standard Deviation 24.6	408 ms Standard Deviation 20.8

SECONDARY outcome

Timeframe: 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.

Average QTc Bazett over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=35 Participants Placebo inhaled via Turbuhaler
QTcB, Average Effect Over 0 - 4 h Post-dose	398 ms Standard Deviation 19.9	397 ms Standard Deviation 22.3	402 ms Standard Deviation 21.2	395 ms Standard Deviation 21.4	406 ms Standard Deviation 24.4	395 ms Standard Deviation 19.8

SECONDARY outcome

Timeframe: 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.

Maximum tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=34 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=34 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
Tremor, Peak Effect Over 0 - 4 h Post-dose	0.06 Score on a scale Standard Deviation 0.24	0.06 Score on a scale Standard Deviation 0.24	0.17 Score on a scale Standard Deviation 0.45	0.11 Score on a scale Standard Deviation 0.32	0.47 Score on a scale Standard Deviation 0.66	0.03 Score on a scale Standard Deviation 0.17

SECONDARY outcome

Timeframe: 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.

Average tremor score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h.

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=34 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=34 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
Tremor, Average Effect Over 0 - 4 h Post-dose	0.00 Score on a scale Standard Deviation 0.02	0.02 Score on a scale Standard Deviation 0.08	0.04 Score on a scale Standard Deviation 0.11	0.05 Score on a scale Standard Deviation 0.18	0.16 Score on a scale Standard Deviation 0.34	0.01 Score on a scale Standard Deviation 0.06

SECONDARY outcome

Timeframe: 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.

Maximum palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=34 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=34 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
Palpitations, Peak Effect Over 0 - 4 h Post-dose	0.03 Score on a scale Standard Deviation 0.17	0.03 Score on a scale Standard Deviation 0.17	0.09 Score on a scale Standard Deviation 0.37	0.00 Score on a scale Standard Deviation 0.00	0.18 Score on a scale Standard Deviation 0.52	0.00 Score on a scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: 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.

Average palpitation score (4 grade scale: 0=no, 1=mild, 2=moderate or 3=severe) over 4 h

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=34 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 Participants Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=34 Participants Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=34 Participants Placebo inhaled via Turbuhaler
Palpitations, Average Effect Over 0 - 4 h Post-dose	0.00 Score on a scale Standard Deviation 0.02	0.01 Score on a scale Standard Deviation 0.05	0.02 Score on a scale Standard Deviation 0.08	0.00 Score on a scale Standard Deviation 0.00	0.11 Score on a scale Standard Deviation 0.33	0.00 Score on a scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: 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.

Maximum plasma concentration of AZD3199 measured

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg Formoterol 36 Mcg inhaled via Turbuhaler	Placebo Placebo inhaled via Turbuhaler
Plasma AZD3199 Cmax	0.99 nmol/L Interval 0.21 to 2.83	5.39 nmol/L Interval 1.32 to 12.4	24.55 nmol/L Interval 8.99 to 44.3	—	—	—

SECONDARY outcome

Timeframe: 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.

Area under the plasma concentration curve from time 0 to 24 h post-dose

Outcome measures

Measure	AZD3199 120 mcg n=35 Participants AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 Participants AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 Participants AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg Formoterol 36 Mcg inhaled via Turbuhaler	Placebo Placebo inhaled via Turbuhaler
Plasma AZD3199 AUC0-24	1.83 nmol*h/L Interval 0.3 to 5.2	9.75 nmol*h/L Interval 2.9 to 23.5	46.06 nmol*h/L Interval 14.6 to 106.2	—	—	—

Adverse Events

AZD3199 120 mcg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

AZD3199 480 mcg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

AZD3199 1920 mcg

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Formoterol 9 mcg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Formoterol 36 mcg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	AZD3199 120 mcg n=36 participants at risk AZD3199 120 Mcg inhaled via Turbuhaler	AZD3199 480 mcg n=35 participants at risk AZD3199 480 Mcg inhaled via Turbuhaler	AZD3199 1920 mcg n=35 participants at risk AZD3199 1920 Mcg inhaled via Turbuhaler	Formoterol 9 mcg n=35 participants at risk Formoterol 9 Mcg inhaled via Turbuhaler	Formoterol 36 mcg n=35 participants at risk Formoterol 36 Mcg inhaled via Turbuhaler	Placebo n=36 participants at risk Placebo inhaled via Turbuhaler
Nervous system disorders Headache	2.8% 1/36	8.6% 3/35	11.4% 4/35	5.7% 2/35	8.6% 3/35	5.6% 2/36
Infections and infestations Nasopharyngitis	8.3% 3/36	2.9% 1/35	11.4% 4/35	0.00% 0/35	2.9% 1/35	11.1% 4/36
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/36	0.00% 0/35	11.4% 4/35	0.00% 0/35	0.00% 0/35	0.00% 0/36

Additional Information

Carin Jorup, MSD

AstraZeneca

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee Prior to any publication or disclosure, the PI provides AstraZeneca with preliminary data and drafts and with the proposed final manuscript. AstraZeneca shall have a period of 30 days from receipt of the proposed final manuscript to review it and may within such time frame require that submission for publication or disclosure be delayed.
• Publication restrictions are in place

Restriction type: OTHER