Trial Outcomes & Findings for Effect of Roflumilast on Lung Function in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Salmeterol: The EOS Study (BY217/M2-127) (NCT NCT00313209)

NCT ID: NCT00313209

Last Updated: 2016-12-14

Results Overview

Mean change from baseline during the treatment period in pre-bronchodilator FEV1 \[L\]

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

933 participants

Primary outcome timeframe

Change from baseline over 24 weeks of treatment

Results posted on

2016-12-14

Participant Flow

Participant milestones

Participant milestones
Measure	Roflumilast Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Placebo Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Overall Study STARTED	466	467
Overall Study COMPLETED	359	385
Overall Study NOT COMPLETED	107	82

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Roflumilast on Lung Function in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Salmeterol: The EOS Study (BY217/M2-127)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Roflumilast n=466 Participants Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Placebo n=467 Participants Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Total n=933 Participants Total of all reporting groups
Age, Continuous	64.9 years STANDARD_DEVIATION 8.7 • n=93 Participants	64.9 years STANDARD_DEVIATION 9.3 • n=4 Participants	64.9 years STANDARD_DEVIATION 9.0 • n=27 Participants
Gender Female	147 Participants n=93 Participants	168 Participants n=4 Participants	315 Participants n=27 Participants
Gender Male	319 Participants n=93 Participants	299 Participants n=4 Participants	618 Participants n=27 Participants

PRIMARY outcome

Timeframe: Change from baseline over 24 weeks of treatment

Population: ITT (Intention to Treat) analysis. Number of participants analyzed = number of participants with data available.

Mean change from baseline during the treatment period in pre-bronchodilator FEV1 \[L\]

Outcome measures

Outcome measures
Measure	Roflumilast n=456 Participants Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Placebo n=463 Participants Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)	39 mL Standard Error 9	-10 mL Standard Error 9

SECONDARY outcome

Timeframe: Change from baseline over 24 weeks of treatment

Population: ITT analysis. Number of participants analyzed = number of participants with data available.

Mean change from baseline during the treatment period in post-bronchodilator FEV1 \[L\]

Outcome measures

Outcome measures
Measure	Roflumilast n=452 Participants Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Placebo n=460 Participants Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Post-bronchodilator FEV1	68 mL Standard Error 9	8 mL Standard Error 9

SECONDARY outcome

Timeframe: 24 weeks treatment period

Population: ITT analysis

Mean rate of COPD exacerbations requiring rescue medication of 3 or more puffs/day on at least 2 consecutive days (=mild COPD exacerbations), or requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year. A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management \[ATS / ERS 2005\].

Outcome measures

Outcome measures
Measure	Roflumilast n=466 Participants Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Placebo n=467 Participants Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
COPD Exacerbation Rate (Mild, Moderate or Severe)	1.9 exacerbations per patient per year Interval 1.5 to 2.5	2.4 exacerbations per patient per year Interval 1.9 to 3.1

SECONDARY outcome

Timeframe: Change from baseline over 24 weeks of treatment

Population: ITT analysis. Number of participants analyzed = number of participants with data available.

The TDI is a recognized questionnaire to measure dyspnea in an out patient COPD population. At baseline, 3 components of dyspnea, each graded with 4 questions, were asked: - Functional Impairment - Magnitude of Task - Magnitude of Effort At each of the post-randomization visits questions from the TDI were asked related to 3 components: Change in - Functional Impairment - Magnitude of Task - Magnitude of Effort Each question in the TDI is graded from -3 (major deterioration) to +3 (major improvement). This results in a TDI Focal Score ranging from -9 to +9.

Outcome measures

Outcome measures
Measure	Roflumilast n=454 Participants Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Placebo n=460 Participants Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Transition Dyspnea Index (TDI) Focal Score	1.2 scores on a scale Standard Error 0.1	1.1 scores on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: Change from baseline over 24 weeks of treatment

Population: ITT analysis. Number of participants analyzed = number of participants with data available.

Mean change from baseline during the treatment period in SOBQ. This is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living. The questions were administered at visits V0, V2, V3, V4, V5, V6 and Vend to assess the perceived shortness of breath of the patient. For each activity listed in the questionnaire the patient should rate his/her breathlessness on a scale between zero and five, where zero is "not at all breathless" and five is "maximally breathless or too breathless to do the activity".

Outcome measures

Outcome measures
Measure	Roflumilast n=454 Participants Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Placebo n=461 Participants Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Shortness of Breath Questionnaire (SOBQ) Total Score	-0.6 scores on a scale Standard Error 0.7	-1.1 scores on a scale Standard Error 0.7

Adverse Events

Roflumilast

Serious events: 36 serious events

Other events: 165 other events

Deaths: 0 deaths

Placebo

Serious events: 42 serious events

Other events: 143 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Roflumilast n=466 participants at risk Roflumilast 500 µg, once daily, oral and salmeterol 50 µg, twice daily, inhaled	Placebo n=467 participants at risk Placebo, once daily, oral and salmeterol 50 µg, twice daily, inhaled
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	15.0% 70/466 • Number of events 81 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.	22.1% 103/467 • Number of events 126 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.
Gastrointestinal disorders Diarrhoea	8.2% 38/466 • Number of events 41 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.	3.2% 15/467 • Number of events 16 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.
Gastrointestinal disorders Nausea	5.4% 25/466 • Number of events 26 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.	0.21% 1/467 • Number of events 1 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.
Infections and infestations Nasopharyngitis	7.1% 33/466 • Number of events 39 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.	7.5% 35/467 • Number of events 43 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.
Investigations Weight decreased	8.4% 39/466 • Number of events 39 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.	1.1% 5/467 • Number of events 5 • 24 weeks treatment period The Safety Set was based on all randomized patients who took at least one dose of the investigational drug after randomization.

Additional Information

AstraZeneca Clinical Study Information Center

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The study results may be published and/or presented at scientific meetings. Prior to any submission, all manuscripts/abstracts must be presented to the sponsor for possible comments.
Publication restrictions are in place

Restriction type: OTHER