Trial Outcomes & Findings for Phase IV O2 Consumption Study in COPD Patients. (NCT NCT02533505)

NCT ID: NCT02533505

Last Updated: 2018-07-30

Results Overview

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 51 participants
• Primary outcome timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
• Results posted on: 2018-07-30

Participant Flow

This study was conducted at 5 sites in the United States (US) between 25 August 2015 and 12 August 2016.

This was a Phase 4, randomized, double-blind, multi-center, placebo-controlled, 2 way cross over study to evaluate changes in oxygen consumption and cardiac function in COPD patients with resting hyperinflation after administration of Symbicort pMDI. The study consisted of 5 site visits and 1 phone visit for a total study duration of 6 weeks.

Participant milestones

Measure	Symbicort pMDI/Placebo/Symbicort pMDI/Placebo The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo/Symbicort pMDI/Placebo/Symbicort pMDI The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Overall Study STARTED	26	25
Overall Study COMPLETED	23	24
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase IV O2 Consumption Study in COPD Patients.

Baseline characteristics by cohort

Measure	Over All n=51 Participants
Age, Continuous	62.9 Years STANDARD_DEVIATION 8.32 • n=5 Participants
Age, Customized <50	3 Participants n=5 Participants
Age, Customized >=50 - <65	27 Participants n=5 Participants
Age, Customized >=65	21 Participants n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Race/Ethnicity, Customized Black Or African American	13 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants
Race/Ethnicity, Customized White	37 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Consumption (VO2; Obtained Via a Metabolic Cart)	11.366 mL/min Interval 5.148 to 17.584	1.252 mL/min Interval -4.867 to 7.371

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Pulse (Defined as VO2/Heart Rate [HR]; VO2 is Obtained Via a Metabolic Cart; Used as a Surrogate for Stroke Volume)	0.256 mL/min/beats/min Interval 0.166 to 0.345	0.168 mL/min/beats/min Interval 0.081 to 0.256

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter HR	-2.481 ΔHR: beats/min Interval -3.709 to -1.253	-2.831 ΔHR: beats/min Interval -4.049 to -1.614

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and IC (using an slow vital capacity [SVC] maneuver; IC/total lung capacity [TLC] will be used as a measure of resting hyperinflation). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change From Pre-dose (Visit 2)to Post-dose (Visit 5) Assessment in Spirometry. ΔFEV1	0.187 FEV1: L; ΔFVC: L; ΔIC: L Interval 0.151 to 0.224	-0.004 FEV1: L; ΔFVC: L; ΔIC: L Interval -0.04 to 0.033
Change From Pre-dose (Visit 2)to Post-dose (Visit 5) Assessment in Spirometry. ΔFVC	0.259 FEV1: L; ΔFVC: L; ΔIC: L Interval 0.196 to 0.322	-0.052 FEV1: L; ΔFVC: L; ΔIC: L Interval -0.115 to 0.011
Change From Pre-dose (Visit 2)to Post-dose (Visit 5) Assessment in Spirometry. ΔIC	0.256 FEV1: L; ΔFVC: L; ΔIC: L Interval 0.21 to 0.302	-0.024 FEV1: L; ΔFVC: L; ΔIC: L Interval -0.07 to 0.022

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Population: Units of measure: Vt/Ti: mL/sec

Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in mean inspiratory flow (tidal volume [Vt]/inspiratory time [Ti]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change in Vt/Ti	26.533 mL/sec Interval 6.73 to 46.335	3.217 mL/sec Interval -16.349 to 22.784

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). Modified Borg scale for dyspnea was self-administered at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21). The Borg scale is a 1-item instrument through which a subject reports dyspnea symptoms on a scale of 0-10 to quantify the intensity of dyspnea (where 10 is most intense).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in the Modified Borg Scale for Dyspnea	-0.452 units on a scale Interval -0.703 to -0.202	-0.248 units on a scale Interval -0.499 to 0.003

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter VCO2	5.994 ΔVCO2: mL/min Interval -1.277 to 13.264	-4.251 ΔVCO2: mL/min Interval -11.417 to 2.915

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter SaO2	0.422 SaO2: % Interval 0.034 to 0.81	0.181 SaO2: % Interval -0.206 to 0.568

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Population: ΔRR: breaths/min

For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change in RR	-0.193 breaths/min Interval -0.691 to 0.305	-0.430 breaths/min Interval -0.92 to 0.06

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Population: ΔTi/Ttot is measured as a ratio.

Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in fractional inspiratory time (Ti/total cycle time [Ttot]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change in Ti/Ttot	0.012 ratio Interval -0.003 to 0.027	-0.004 ratio Interval -0.019 to 0.011

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Population: Units of measure: ΔVt: mL

Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in tidal volume (Vt). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change in Vt	71.904 mL Interval 47.804 to 96.005	14.281 mL Interval -9.475 to 38.036

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Population: Units of measure: ΔVe: mL/min.

Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in minute ventilation (Ve). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change in Ve	838.232 mL/min Interval 449.034 to 1227.431	-23.924 mL/min Interval -410.389 to 362.541

SECONDARY outcome

Timeframe: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.

Population: ΔFEV1/FVC calculated as ratio.

FEV1/FVC. For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).

Outcome measures

Measure	Symbicort pMDI n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 Participants The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Spirometry.	0.017 ratio Interval 0.008 to 0.026	-0.002 ratio Interval -0.011 to 0.007

Adverse Events

Symbicort pMDI

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Measure	Symbicort pMDI n=51 participants at risk The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 participants at risk The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Infections and infestations Pneumonia	0.00% 0/51	2.0% 1/51 • Number of events 1

Other adverse events

Measure	Symbicort pMDI n=51 participants at risk The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.	Placebo n=51 participants at risk The study utilized a 2-treatment, 4-period, cross-over design with 2 sequences. Each patient was randomized to 1 of 2 sequences (ABAB or BABA), where 'A', 'B' denote the active treatment or placebo treatment, respectively. Patients randomized to sequence ABAB received treatment A, B, A, and B at Visit 2 to Visit 5, respectively. Patients randomized to sequence BABA received B, A, B, and A at Visit 2 to Visit 5, respectively.
Eye disorders Cataract	2.0% 1/51 • Number of events 1	0.00% 0/51
Gastrointestinal disorders Abdominal pain upper	0.00% 0/51	2.0% 1/51 • Number of events 1
Gastrointestinal disorders Nausea	2.0% 1/51 • Number of events 1	0.00% 0/51
General disorders Non-cardiac chest pain	0.00% 0/51	2.0% 1/51 • Number of events 1
Infections and infestations Bronchitis	0.00% 0/51	2.0% 1/51 • Number of events 1
Infections and infestations Diverticulitis	0.00% 0/51	2.0% 1/51 • Number of events 1
Infections and infestations Ear infection	2.0% 1/51 • Number of events 1	0.00% 0/51
Infections and infestations Gastroenteritis viral	0.00% 0/51	2.0% 1/51 • Number of events 1
Infections and infestations Hordeolum	0.00% 0/51	2.0% 1/51 • Number of events 1
Infections and infestations Nasopharyngitis	2.0% 1/51 • Number of events 1	2.0% 1/51 • Number of events 1
Infections and infestations Pharyngitis streptococcal	2.0% 1/51 • Number of events 1	0.00% 0/51
Infections and infestations Sinusitis	2.0% 1/51 • Number of events 1	0.00% 0/51
Infections and infestations Urinary tract infection	2.0% 1/51 • Number of events 1	0.00% 0/51
Injury, poisoning and procedural complications Post procedural complication	2.0% 1/51 • Number of events 1	0.00% 0/51
Investigations Blood glucose increased	0.00% 0/51	2.0% 1/51 • Number of events 1
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/51	2.0% 1/51 • Number of events 1
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/51	2.0% 1/51 • Number of events 1
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/51	2.0% 1/51 • Number of events 1
Musculoskeletal and connective tissue disorders Back pain	2.0% 1/51 • Number of events 1	2.0% 1/51 • Number of events 1
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/51	2.0% 1/51 • Number of events 1
Nervous system disorders Headache	0.00% 0/51	2.0% 1/51 • Number of events 1
Nervous system disorders Migraine	2.0% 1/51 • Number of events 1	0.00% 0/51
Psychiatric disorders Confusional state	0.00% 0/51	2.0% 1/51 • Number of events 1
Psychiatric disorders Depression	0.00% 0/51	2.0% 1/51 • Number of events 1
Renal and urinary disorders Urinary incontinence	2.0% 1/51 • Number of events 1	0.00% 0/51
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/51	2.0% 1/51 • Number of events 1
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	5.9% 3/51 • Number of events 3	0.00% 0/51
Respiratory, thoracic and mediastinal disorders Cough	2.0% 1/51 • Number of events 1	0.00% 0/51
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.9% 3/51 • Number of events 3	2.0% 1/51 • Number of events 2
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.0% 1/51 • Number of events 1	0.00% 0/51
Skin and subcutaneous tissue disorders Blister	2.0% 1/51 • Number of events 1	0.00% 0/51
Vascular disorders Deep vein thrombosis	0.00% 0/51	2.0% 1/51 • Number of events 1
Vascular disorders Hypertension	0.00% 0/51	3.9% 2/51 • Number of events 2

Additional Information

AstraZeneca Clinical

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place