Trial Outcomes & Findings for Evaluation of Onset of Effect in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) Treated With Symbicort® Compared to Seretide® (NCT NCT00542880)

NCT ID: NCT00542880

Last Updated: 2012-08-30

Results Overview

The change from baseline in PEF was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and all days of treatment, with baseline as covariate.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 442 participants
• Primary outcome timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days
• Results posted on: 2012-08-30

Participant Flow

706 subjects were enrolled; 264 were not randomised: 190 with eligibility not fulfilled, 11 with adverse events, 4 with discontinuation criteria, 40 voluntary discontinuations, 2 lost to follow-ups, 6 non-compliance, 1 for safety reasons, 10 with other reasons not specified. 442 subjects were randomised

Participant milestones

Measure	Symbicort Turbuhaler First, Then Seretide Diskus Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg First, then Seretide Diskus (salmeterol/fluticasone) 50/500 μg	Seretide Diskus First, Then Symbicort Turbuhaler Seretide Diskus (salmeterol/fluticasone) 50/500 μg First, then Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg
Period 1 STARTED	217	225
Period 1 COMPLETED	211	213
Period 1 NOT COMPLETED	6	12
Period 2 STARTED	211	213
Period 2 COMPLETED	204	203
Period 2 NOT COMPLETED	7	10
Period 3 STARTED	204	203
Period 3 COMPLETED	204	201
Period 3 NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Symbicort Turbuhaler First, Then Seretide Diskus Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg First, then Seretide Diskus (salmeterol/fluticasone) 50/500 μg	Seretide Diskus First, Then Symbicort Turbuhaler Seretide Diskus (salmeterol/fluticasone) 50/500 μg First, then Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg
Period 1 Eligibility criteria not fulfilled	2	6
Period 1 Adverse Event	2	2
Period 1 Development of study-specific criteria	1	2
Period 1 Withdrawal by Subject	1	1
Period 1 Protocol Violation	0	1
Period 2 Adverse Event	5	7
Period 2 Eligibility not fulfilled	0	1
Period 2 Discontinuation criteria	2	0
Period 2 Severe non-compliance	0	1
Period 2 Other	0	1
Period 3 Adverse Event	0	2

Baseline Characteristics

Evaluation of Onset of Effect in Patients With Severe Chronic Obstructive Pulmonary Disease (COPD) Treated With Symbicort® Compared to Seretide®

Baseline characteristics by cohort

Measure	Symbicort Turbuhaler First, Then Seretide Diskus n=217 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg First, then Seretide Diskus (salmeterol/fluticasone) 50/500 μg	Seretide Diskus First, Then Symbicort Turbuhaler n=225 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg First, then Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Total n=442 Participants Total of all reporting groups
Age Continuous	62.9 years n=5 Participants	63.2 years n=7 Participants	63.1 years n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	71 Participants n=7 Participants	126 Participants n=5 Participants
Sex: Female, Male Male	162 Participants n=5 Participants	154 Participants n=7 Participants	316 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from baseline in PEF was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and all days of treatment, with baseline as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=385 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=390 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Peak Expiratory Flow (PEF) 5 Minutes After Morning Dose	15.1 liters/minute Standard Deviation 28.5	13.4 liters/minute Standard Deviation 28.2

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=416 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=425 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
PEF Before Morning Dose	4.8 Liters/minutes Standard Deviation 28.2	7.9 Liters/minutes Standard Deviation 24

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=377 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=389 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
PEF 15 Minutes After Morning Dose	19.9 Liters/minute Standard Deviation 30.3	16.7 Liters/minute Standard Deviation 28.5

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=418 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=426 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
PEF Before Evening Dose	4 Liters/minute Standard Deviation 24.3	1.8 Liters/minute Standard Deviation 50

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=280 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=269 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Forced Expiratory Volume in 1 Second (FEV1) Before Morning Dose	0.0310 Liters Standard Deviation 0.2460	0.0590 Liters Standard Deviation 0.2310

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=249 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=249 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
FEV1 15 Minutes After Morning Dose	0.1220 Liters Standard Deviation 0.2530	0.1030 Liters Standard Deviation 0.3720

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=248 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=243 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
FEV1 Before Evening Dose	0.1470 Liters Standard Deviation 0.2470	0.1060 Liters Standard Deviation 0.2010

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with pre-dose run-in/washout as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=279 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=279 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Change in PEF From Before Dose to 5 Minutes After Dose in the Morning	0.0160 Liters/minute Standard Deviation 0.2	0.0030 Liters/minute Standard Deviation 0.299

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=368 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=376 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Change in PEF From Before Dose to 15 Minutes After Dose in the Morning	11.6 Liters/minute Standard Deviation 16.2	6.1 Liters/minute Standard Deviation 16.5

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=368 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=376 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Change in FEV1from Before Dose to 5 Minutes After Dose in the Morning	15.8 Liters Standard Deviation 20.8	9.6 Liters Standard Deviation 19.9

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from pre-dose was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with mean pre-dose run-in/washout as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=233 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=238 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Change in FEV1 From Before Dose to 15 Minutes After Dose in the Morning	0.0930 Liters Standard Deviation 0.1870	0.0280 Liters Standard Deviation 0.1630

SECONDARY outcome

Timeframe: Baseline (run-in, and washout) and day 1 of treatment period

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=233 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=238 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Change in FEV1 From Before Dose to 5 Minutes After Dose at the Clinic	0.1120 Liters Standard Deviation 0.1950	0.0440 Liters Standard Deviation 0.1640

SECONDARY outcome

Timeframe: Baseline (run-in, and washout) and day 1 of treatment period

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from pre-dose was calculated using the pre-dose baseline value (run-in and washout period respectively), and pre-dose value at day 1, with pre-dose run-in/washout as covariate.

Outcome measures

Measure	Symbicort Turbuhaler n=415 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=426 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Change in Forced Vital Capacity (FVC) From Before Dose to5 Minutes After Dose at the Clinic	0.0950 Liters Standard Deviation 0.1370	0.0490 Liters Standard Deviation 0.1060

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best.

Outcome measures

Measure	Symbicort Turbuhaler n=415 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=426 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Capacity of Daily Living in the Morning (CDLM) (Change From Pre to End of Treatment)	0.1920 units on a scale Standard Deviation 0.2530	0.1240 units on a scale Standard Deviation 0.2310

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 5 with 0=worst and 5 = best.

Outcome measures

Measure	Symbicort Turbuhaler n=319 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=311 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
Difficulty in Getting Out From Bed (MASQ) (Change From Pre to End of Treatment)	0.21 Units on a scale Standard Deviation 0.64	0.14 Units on a scale Standard Deviation 0.75

SECONDARY outcome

Timeframe: Baseline (daily records during run-in, and washout) and daily records during the treatment period of 7 days

Population: Includes all subjects with at least one dose of study medication and who contribute sufficient data for the endpoint to be calculated.

The change from baseline was calculated using the average over baseline (the last 7 days of run-in and washout period respectively), and over all days of treatment, with baseline as covariate. Score scale 0 - 6 with 0=worst and 6 = best.

Outcome measures

Measure	Symbicort Turbuhaler n=394 Participants Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=396 Participants Seretide Diskus (salmeterol/fluticasone) 50/500 μg
The Clinical Chronic Obstructive Pulmonary Disease (COPD) Questionnaire (Change From Pre to End of Treatment)	0.24 Units on a scale Standard Deviation 0.75	0.19 Units on a scale Standard Deviation 0.73

Adverse Events

Symbicort Turbuhaler

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Seretide Diskus

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Symbicort Turbuhaler n=420 participants at risk Symbicort Turbuhaler (budesonide/formoterol) 320/9 μg	Seretide Diskus n=429 participants at risk Seretide Diskus (salmeterol/fluticasone) 50/500 μg
General disorders Gait disturbance	0.24% 1/420	0.00% 0/429
Respiratory, thoracic and mediastinal disorders Chronic obstructive oulmonary disease	0.48% 2/420	0.23% 1/429

Other adverse events

Adverse event data not reported

Additional Information

Gerard Lynch

AstraZeneca

Email: AZTrial_Results_Posting@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