Trial Outcomes & Findings for Validation of a New Shortness of Breath With Daily Activities Questionnaire in Patients With Chronic Obstructive Pulmonary Disease (NCT NCT00984659)

NCT ID: NCT00984659

Last Updated: 2018-08-29

Results Overview

Cronbach's alpha (CA) is a measure of the IC of the 13-item SOBDA questionnaire (completed via electronic diary by a sample of participants). It is the ratio of the variance (var.) of the sum of the individual scores and the var. of the total score. The var. of the sum of a group of independent variables is the sum of their var.; thus, if the variables are positively correlated, the var. of the sum will be increased. If the items making up the score are identical and so perfectly correlated, CA=1. If the items are independent, CA=0. Higher scores indicate a more reliable (precise) instrument.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 366 participants
• Primary outcome timeframe: Day 1 of the 2-week Run-in Period
• Results posted on: 2018-08-29

Participant Flow

The number of participants "enrolled" in the Protocol reflects the number of participants starting treatment in the Double-blind Treatment Period.

After Screening (Visit 1), the study commenced with a 2-week Run-in Period, during which participants were permitted to use albuterol and/or ipratropium as rescue medication. Eligible participants at Visit 2 were randomized to receive one of three treatments in the 6-week Double-blind Treatment Period.

Participant milestones

Measure	Albuterol and/or Ipratropium: Run-in Period Participants were permitted to use albuterol and/or ipratropium as rescue medication during the 2-week Run-in Period	Placebo: Double-blind Treatment Period Matching placebo via DISKUS, administered as one inhalation twice daily (BID) during the 6-week Double-blind Treatment Period	SAL 50 mcg: Double-blind Treatment Period Salmeterol xinafoate (SAL) 50 micrograms (mcg) per inhalation via DISKUS, administered as one inhalation BID during the 6-week Double-blind Treatment Period	FSC 250/50 mcg: Double-blind Treatment Period Fluticasone propionate and salmeterol xinafoate fixed dose combination product (FSC) 250/50 mcg per inhalation via DISKUS, administered as one inhalation BID during the 6-week Double-blind Treatment Period
2-week Run-in Period STARTED	418	0	0	0
2-week Run-in Period COMPLETED	366	0	0	0
2-week Run-in Period NOT COMPLETED	52	0	0	0
6-week Double-blind Treatment Period STARTED	0	75	152	139
6-week Double-blind Treatment Period COMPLETED	0	69	141	126
6-week Double-blind Treatment Period NOT COMPLETED	0	6	11	13

Reasons for withdrawal

Measure	Albuterol and/or Ipratropium: Run-in Period Participants were permitted to use albuterol and/or ipratropium as rescue medication during the 2-week Run-in Period	Placebo: Double-blind Treatment Period Matching placebo via DISKUS, administered as one inhalation twice daily (BID) during the 6-week Double-blind Treatment Period	SAL 50 mcg: Double-blind Treatment Period Salmeterol xinafoate (SAL) 50 micrograms (mcg) per inhalation via DISKUS, administered as one inhalation BID during the 6-week Double-blind Treatment Period	FSC 250/50 mcg: Double-blind Treatment Period Fluticasone propionate and salmeterol xinafoate fixed dose combination product (FSC) 250/50 mcg per inhalation via DISKUS, administered as one inhalation BID during the 6-week Double-blind Treatment Period
2-week Run-in Period Adverse Event	8	0	0	0
2-week Run-in Period Protocol Violation	5	0	0	0
2-week Run-in Period Study Closed/Terminated	2	0	0	0
2-week Run-in Period Lost to Follow-up	3	0	0	0
2-week Run-in Period Physician Decision	10	0	0	0
2-week Run-in Period Withdrawal by Subject	10	0	0	0
2-week Run-in Period Did Not Meet Continuation Criteria	14	0	0	0
6-week Double-blind Treatment Period Adverse Event	0	3	3	7
6-week Double-blind Treatment Period Lack of Efficacy	0	2	0	1
6-week Double-blind Treatment Period Protocol Violation	0	0	0	4
6-week Double-blind Treatment Period Study Closed/Terminated	0	0	1	0
6-week Double-blind Treatment Period Withdrawal by Subject	0	1	7	1

Baseline Characteristics

Validation of a New Shortness of Breath With Daily Activities Questionnaire in Patients With Chronic Obstructive Pulmonary Disease

Baseline characteristics by cohort

Measure	Placebo n=75 Participants Matching placebo via DISKUS, administered as one inhalation twice daily (BID)	SAL 50 mcg n=152 Participants Salmeterol xinafoate (SAL) 50 micrograms (mcg) per inhalation via DISKUS, administered as one inhalation BID	FSC 250/50 mcg n=139 Participants Fluticasone propionate and salmeterol xinafoate fixed dose combination product (FSC) 250/50 mcg per inhalation via DISKUS, administered as one inhalation BID	Albuterol and/or Ipratropium: Run-in Failure n=52 Participants Participants who entered the 2-week Run-in Period, during which they were permitted to use albuterol and/or ipratropium as rescue medication, but then failed to be randomized, or were randomized but did not receive a dose of study medication	Total n=418 Participants Total of all reporting groups
Age, Continuous	62.8 Years STANDARD_DEVIATION 9.82 • n=93 Participants	60.1 Years STANDARD_DEVIATION 9.58 • n=4 Participants	60.2 Years STANDARD_DEVIATION 9.45 • n=27 Participants	63.8 Years STANDARD_DEVIATION 9.61 • n=483 Participants	61.1 Years STANDARD_DEVIATION 9.65 • n=36 Participants
Sex: Female, Male Female	29 Participants n=93 Participants	63 Participants n=4 Participants	60 Participants n=27 Participants	27 Participants n=483 Participants	179 Participants n=36 Participants
Sex: Female, Male Male	46 Participants n=93 Participants	89 Participants n=4 Participants	79 Participants n=27 Participants	25 Participants n=483 Participants	239 Participants n=36 Participants
Race/Ethnicity, Customized African American/African Heritage	9 participants n=93 Participants	12 participants n=4 Participants	12 participants n=27 Participants	8 participants n=483 Participants	41 participants n=36 Participants
Race/Ethnicity, Customized Asian	1 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	1 participants n=36 Participants
Race/Ethnicity, Customized White	65 participants n=93 Participants	140 participants n=4 Participants	127 participants n=27 Participants	44 participants n=483 Participants	376 participants n=36 Participants

PRIMARY outcome

Timeframe: Day 1 of the 2-week Run-in Period

Population: Run-in Population: all participants who completed Visit 2 (Day 1 of Treatment Period), including those who were not randomized, were randomized but did not receive a dose of study medication, and those who were randomized and received study medication. Participants with a score for each SOBDA item on Day 1 of the 2-week Run-in Period were analyzed.

Cronbach's alpha (CA) is a measure of the IC of the 13-item SOBDA questionnaire (completed via electronic diary by a sample of participants). It is the ratio of the variance (var.) of the sum of the individual scores and the var. of the total score. The var. of the sum of a group of independent variables is the sum of their var.; thus, if the variables are positively correlated, the var. of the sum will be increased. If the items making up the score are identical and so perfectly correlated, CA=1. If the items are independent, CA=0. Higher scores indicate a more reliable (precise) instrument.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=344 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Internal Consistency (IC) of the Shortness of Breath With Daily Activities (SOBDA) Questionnaire in Participants With Chronic Obstructive Pulmonary Disease (COPD) Assessed as Cronbach's Alpha Value	0.892 ratio of variance

PRIMARY outcome

Timeframe: Week 1 and Week 2 of the 2-week Run-in Period

Population: Run-in Population. Data from participants with weekly SOBDA scores at Week 1 and Week 2 of the 2-week Run-in Period and reporting no change on the second weekly PGAC were analyzed.

T-RR=stability during repeat measures over time in a stable population. SOBDA score was determined by the 13-item (it.) scoring algorithm, assigning a weekly mean score of 1-4 (higher scores=more severe breathlessness with daily activities) based on the mean of 7 days of data (or >=4 days). Daily total score is computed from the mean of the participant's (par.) scores on the 13 it. (>=7 it. must have non-missing responses). Only scores of stable par. (indicating no change [score=3] on the par.-completed Patient Global Assessment of Change [PGAC]; 1 [ much worse] to 5 [much better]) were used.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=152 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Test-retest Reliability (T-RR) of SOBDA Scores Measured as the Difference in the SOBDA Weekly Score Between Week 1 and Week 2 of the 2-week Run-in Period	0.01 scores on a scale Standard Deviation 0.244

PRIMARY outcome

Timeframe: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)

Population: Run-in Population. Participants with a SOBDA Baseline score and the indicated assessment at Visit 2 were analyzed. One participant who rated their own trouble breathing had missing data for the physician assessment.

Convergent validity is defined as the ability of the SOBDA questionnaire to measure required information and was assessed by examining the relationship between the SOBDA score and the participant/physician-completed mMRC Dyspnea Scale assessments. The physician/participant rated the degree of the participant's dyspnea (trouble breathing) on the 5-point mMRC scale (0, none; 4, very severe). Spearman's rank correlation coefficient assesses if the relationship between two variables is monotone. A correlation of +1 or -1 will occur if one variable is a perfect monotone of the other.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=340 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Convergent Validity for the SOBDA Questionnaire Measured as Correlations of the Baseline SOBDA Score With Participant-completed Modified Medical Research Council (mMRC) and Physician-completed mMRC Scores at Visit 2 Physician-completed mMRC, n=339	0.24 Spearman rank correlation coefficient
Convergent Validity for the SOBDA Questionnaire Measured as Correlations of the Baseline SOBDA Score With Participant-completed Modified Medical Research Council (mMRC) and Physician-completed mMRC Scores at Visit 2 Participant-completed mMRC, n=340	0.29 Spearman rank correlation coefficient

PRIMARY outcome

Timeframe: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)

Population: Run-in Population. Participants with a SOBDA Baseline score and the indicated assessment at Visit 2 were analyzed.

Convergent validity is defined as the ability of the SOBDA questionnaire to measure the required information and was assessed by examining the relationship between the SOBDA score with the CGI-S score. Spearman's rank correlation coefficient assesses if the relationship between two variables is monotone. A correlation of +1 or -1 will occur if one variable is a perfect monotone of the other. Clinicians were asked to assess the severity of the participant's dyspnea on the CGI-S scale. This was evaluated on a 1-4 Likert scale: 1 (mild) to 4 (very severe).

Outcome measures

Measure	All Participants: 2-week Run-in Period n=338 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Convergent Validity for the SOBDA Questionnaire Measured as the Correlation of the Baseline SOBDA Score With the Clinician Global Assessment of Dyspnea Severity (CGI-S) Score at Visit 2	0.24 Spearman rank correlation coefficient

PRIMARY outcome

Timeframe: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)

Population: Run-in Population. Participants with a SOBDA Baseline score and the indicated assessment at Visit 2 were analyzed.

Convergent validity is defined as the ability of the SOBDA questionnaire to measure required information and was assessed by examining the relationship between the SOBDA score and the CRQ-SAS dyspnea domain score. Pearson's correlation coefficient is a measure of the linear dependence between 2 variables. A correlation of +1 or -1 will occur if the data from the 2 variables lie exactly on a line. The CRQ is a 20-item instrument measuring 4 domains (each measured on a scale of 1 [maximum impairment] to 7 [no impairment]) of functioning: mastery, fatigue, emotional function, and dyspnea.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=340 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Convergent Validity (CV) for the SOBDA Questionnaire Measured as the Correlation of the Baseline SOBDA Score With the Chronic Respiratory Disease Questionnaire-Self-Administered Standardized (CRQ-SAS) Dyspnea Domain Score at Visit 2	-0.68 Pearson's correlation coefficient

PRIMARY outcome

Timeframe: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)

Population: Run-in Population. Participants with a SOBDA Baseline score and the Physician-completed mMRC score at Visit 2 were analyzed.

SOBDA known group validity refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the PyC mMRC. The physician rated the degree of the participant's dyspnea on the 5-point mMRC scale: 0 (none) to 4 (very severe). Known group validity was confirmed if the SOBDA score increased with increasing values of PyC mMRC, both indicating increased levels of breathlessness.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=339 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Physician-completed (PyC) mMRC Score at Visit 2 PyC mMRC: 0 to 1, n=12	1.78 scores on a scale Standard Error 0.196
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Physician-completed (PyC) mMRC Score at Visit 2 PyC mMRC: 2, n=200	2.08 scores on a scale Standard Error 0.048
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Physician-completed (PyC) mMRC Score at Visit 2 PyC mMRC: 3, n=117	2.28 scores on a scale Standard Error 0.063
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Physician-completed (PyC) mMRC Score at Visit 2 PyC mMRC: 4, n=10	2.73 scores on a scale Standard Error 0.216

PRIMARY outcome

Timeframe: Baseline (last week of the 2-week Run-in Period) and pre-treatment on Visit 2 (Day 1 of the 6-week Treatment Period)

Population: Run-in Population. Participants with a SOBDA Baseline score and the Participant-completed mMRC score at Visit 2 were analyzed.

SOBDA known group validity refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the ParC mMRC. The participant rated the degree of his/her dyspnea on the 5-point mMRC scale: 0 (none) to 4 (very severe). Known group validity was confirmed if the SOBDA score increased with increasing values of ParC mMRC, both indicating increased levels of breathlessness.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=340 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Participant-completed (ParC) mMRC Score at Visit 2 ParC mMRC: 0, n=12	1.92 scores on a scale Standard Error 0.192
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Participant-completed (ParC) mMRC Score at Visit 2 ParC mMRC: 1, n=103	1.94 scores on a scale Standard Error 0.066
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Participant-completed (ParC) mMRC Score at Visit 2 ParC mMRC: 2, n=138	2.20 scores on a scale Standard Error 0.056
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Participant-completed (ParC) mMRC Score at Visit 2 ParC mMRC: 3, n=65	2.26 scores on a scale Standard Error 0.083
Known Group Validity for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of the Participant-completed (ParC) mMRC Score at Visit 2 ParC mMRC: 4, n=22	2.73 scores on a scale Standard Error 0.142

PRIMARY outcome

Timeframe: Baseline (last week of the 2-week Run-in Period) and pre-treatement on Visit 2 (Day 1 of the 6-week Treatment Period)

Population: Run-in Population. Participants with a SOBDA Baseline score and the CGI-S score at Visit 2 were analyzed.

SOBDA KGV refers to the extent to which scores from the SOBDA questionnaire should differentiate participants with varying levels of dyspnea severity. It was assessed by comparing summary measures for the SOBDA score for each indicated level (0, 1, 2, 3, and 4) of the CGI-S score. Clinicians were asked to assess the severity of the participant's dyspnea on the CGI-S scale. This was evaluated on a 1-4 Likert scale: 1 (mild) to 4 (very severe). KGV was confirmed if the SOBDA score increased with increasing values of CGI-S, both indicating increased levels of breathlessness.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=338 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Known Group Validity (KGV) for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of CGI-S Scores at Visit 2 CGI-S: 4, n=5	2.72 scores on a scale Standard Error 0.305
Known Group Validity (KGV) for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of CGI-S Scores at Visit 2 CGI-S: 1, n=19	1.87 scores on a scale Standard Error 0.156
Known Group Validity (KGV) for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of CGI-S Scores at Visit 2 CGI-S: 2, n=236	2.11 scores on a scale Standard Error 0.045
Known Group Validity (KGV) for the SOBDA Questionnaire Measured as the Comparison of the Baseline SOBDA Score in the Indicated Categories of CGI-S Scores at Visit 2 CGI-S: 3, n=78	2.33 scores on a scale Standard Error 0.080

PRIMARY outcome

Timeframe: Days 8, 15, 22, 29, 36, and 43 and Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: Modified Intent-to-Treat (MITT) Population: all participants randomized to treatment who received at least one dose of study medication. Analyses were conducted on data available for each specified time point.

The PGAC is par. completed on a 1-5 scale: 1, much worse; 2, worse; 3, no change; 4, better; 5, much better. Responders were defined as par. with a rating of "better" or "much better" (score of 4 or 5) on the PGAC at the relevant week; non-responders were defined as par. with a response of "much worse," "worse," or "no change" on the PGAC. As pre-specified in the study protocol, results are presented independent of treatment allocation . The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=303 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Responders, Day 8 (Baseline to Week 1), n=293	105 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Non-responders, Day 8 (Baseline to Week 1), n=293	188 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Responders, Day 15 (Week 1 to Week 2), n=303	91 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Non-responders, Day 15 (Week 1 to Week 2), n=303	212 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Responders, Day 22 (Week 2 to Week 3), n=299	83 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Non-responders, Day 22 (Week 2 to Week 3), n=299	216 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Responders, Day 29 (Week 3 to Week 4), n=285	62 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Non-responders, Day 29 (Week 3 to Week 4), n=285	223 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Responders, Day 36 (Week 4 to Week 5), n=277	77 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Non-responders, Day 36 (Week 4 to Week 5), n=277	200 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Responders, Day 43 (Week 5 to Week 6), n=119	31 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Non-responders, Day 43 (Week 5 to Week 6), n=119	88 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Responders, Last Treatment Week, n=151	45 participants
Participants (Par.) Classified as Responders/Non-responders According to the Patient Global Assessment of Change (PGAC) Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/Premature Discontinuation (PD) (the End of the 6-week Treatment Period or PD) Non-responders, Visit 3/PD, n=151	106 participants

PRIMARY outcome

Timeframe: Baseline; Days 8, 15, 22, 29, 36, and 43 and Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

Responsiveness reflects the ability of the SOBDA questionnaire to detect change under conditions of known change. Responders (Rs)=participants (par.) with a rating of "better"/"much better" (score of 4/5) on the PGAC (range; 1 [much worse] to 5 [much better]) at the relevant week; NRs=par. with a response of "much worse," "worse," or "no change" (score of 3). Mean difference between Rs and NRs in the change from the previous week to the current week's SOBDA score was calculated. For Visit 3/PD, the change from Baseline to the last treatment week's SOBDA score for Rs and NRs was calculated.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=223 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Baseline to Day 8, responders, n=105	-0.26 scores on a scale Standard Deviation 0.324
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Baseline to Day 8, non-responders, n=188	-0.01 scores on a scale Standard Deviation 0.254
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 8 to Day 15, responders, n=91	-0.10 scores on a scale Standard Deviation 0.280
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 8 to Day 15, non-responders, n=212	0.01 scores on a scale Standard Deviation 0.222
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 15 to Day 22, responders, n=83	-0.08 scores on a scale Standard Deviation 0.223
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 15 to Day 22, non-responders, n=216	0.02 scores on a scale Standard Deviation 0.183
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 22 to Day 29, responders, n=62	-0.09 scores on a scale Standard Deviation 0.198
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 22 to Day 29, non-responders, n=223	0.01 scores on a scale Standard Deviation 0.193
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 29 to Day 36, responders, n=77	-0.07 scores on a scale Standard Deviation 0.245
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 29 to Day 36, non-responders, n=200	0.03 scores on a scale Standard Deviation 0.169
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 36 to Day 43, responders, n=31	-0.04 scores on a scale Standard Deviation 0.167
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Day 36 to Day 43, non-responders, n=88	0.02 scores on a scale Standard Deviation 0.240
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Baseline to Visit 3/PD, responders, n=45	-0.21 scores on a scale Standard Deviation 0.497
Change From the Previous Week to the Current Week's SOBDA Score by Participant-completed PGAC Response at Days 8, 15, 22, 29, 36, and 43 and at Visit 3/PD (End of the 6-week Treatment Period or PD) Baseline to Visit 3/PD, non-responders, n=106	-0.14 scores on a scale Standard Deviation 0.423

PRIMARY outcome

Timeframe: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

Clinicians were asked to provide their clinical impression regarding change in the participant's shortness of breath by CGI-C. This was evaluated on a 1-5 Likert scale: 1 (much worse) to 5 (much better), with 3 being no change. A CGI-C responder was defined as a participant who had a response of "better" (4) or "much better" (5), and a non-responder was defined as a participant who had a response of "much worse" (1), "worse" (2), or "no change" (3).

Outcome measures

Measure	All Participants: 2-week Run-in Period n=301 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Number of Participants Classified as Responders and Non-responders by Clinician Global Impression of Change Question (CGI-C) Response at Visit 3/PD Responders	120 participants
Number of Participants Classified as Responders and Non-responders by Clinician Global Impression of Change Question (CGI-C) Response at Visit 3/PD Non-responders	181 participants

PRIMARY outcome

Timeframe: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

A CRQ-SAS dyspnea domain responder was defined as a participant who had a score increase of 0.5 units or more for the dyspnea domain of the CRQ-SAS between Visit 2 and Visit 3/Premature Discontinuation. A non-responder was defined as a participant who had a decrease in the score, or an increase of less than 0.5 units.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=301 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Number of Participants Classified as Responders and Non-responders by CRQ-SAS Dyspnea Domain Response at Visit 3/PD Responders	117 participants
Number of Participants Classified as Responders and Non-responders by CRQ-SAS Dyspnea Domain Response at Visit 3/PD Non-responders	184 participants

PRIMARY outcome

Timeframe: Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

A Physician-completed and Participant-completed mMRC responder was defined as a participant who had a score decrease of one unit or more between Visit 2 and Visit 3/Premature Discontinuation. A non-responder was defined as a participant who had the same score or an increase in score.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=301 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Number of Participants Classified as Responders and Non-responders by Physician-completed and Participant-completed mMRC Response at Visit 3/PD Physician-completed mMRC responders	91 participants
Number of Participants Classified as Responders and Non-responders by Physician-completed and Participant-completed mMRC Response at Visit 3/PD Physician-completed mMRC non-responders	210 participants
Number of Participants Classified as Responders and Non-responders by Physician-completed and Participant-completed mMRC Response at Visit 3/PD Participant-completed mMRC responders	92 participants
Number of Participants Classified as Responders and Non-responders by Physician-completed and Participant-completed mMRC Response at Visit 3/PD Participant-completed mMRC non-responders	209 participants

PRIMARY outcome

Timeframe: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

The responsiveness of the SOBDA questionnaire was assessed by comparing score changes between responders and non-responders. The CGI-C is clinician completed on a 1 to 5 scale: 1, much worse; 2, worse; 3, no change; 4, better; 5, much better. Changes in mean SOBDA scores during the last week of treatment in responders and non-responders using definitions based on the CGI-C conducted at Visit 3/Premature Discontinuation were assessed.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=301 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Change From Baseline to Last Treatment Week in the SOBDA Score by CGI-C Responses at Visit 3/PD Responders, n=120	-0.25 scores on a scale Standard Deviation 0.484
Change From Baseline to Last Treatment Week in the SOBDA Score by CGI-C Responses at Visit 3/PD Non-responders, n=181	-0.03 scores on a scale Standard Deviation 0.413

PRIMARY outcome

Timeframe: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

The responsiveness of the SOBDA questionnaire was assessed by comparing score changes of responders (Rs) versus non-responders (NRs). The CRQ-SAS DD includes 5 questions (q.) scored 1 (maximum impairment) to 7 (no impairment). Individual q. were equally weighted, and domain scores (DSs) (range=1-7) were calculated as the mean across the non-missing items within each domain (DSs were calculated although an individual item score was missing). Changes in mean SOBDA scores during the last treatment week in Rs and NRs using definitions based on the CRQ-SAS DD conducted at Visit 3/PD were assessed.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=301 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Change From Baseline to Last Treatment Week in the SOBDA Score by CRQ-SAS Dyspnea Domain (DD) Responses at Visit 3/PD Responders, n=117	-0.32 Scores on a scale Standard Deviation 0.446
Change From Baseline to Last Treatment Week in the SOBDA Score by CRQ-SAS Dyspnea Domain (DD) Responses at Visit 3/PD Non-responders, n=184	0.01 Scores on a scale Standard Deviation 0.416

PRIMARY outcome

Timeframe: Baseline (2-week Run-in Period) and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

The responsiveness of the SOBDA questionnaire was assessed by comparing score changes between responders and non-responders. The mMRC ranges from 0 (no breathlessness except with strenous exercise) to 4 (too breathless to leave the house; breathless when dressing/undressing) and is completed by the clinician or the participant as indicated. Changes in mean SOBDA scores during the last week of treatment in responders and non-responders using definitions based on the Physician-completed (Ph-C) and Participant-completed (Pa-C) mMRC conducted at Visit 3/Premature Discontinuation were assessed.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=301 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
Change From Baseline to Last Treatment Week in the SOBDA Score by Physician-completed mMRC and Participant-completed mMRC Responses at Visit 3/PD Pa-C mMRC, non-responders, n=209	-0.09 Scores on a scale Standard Deviation 0.428
Change From Baseline to Last Treatment Week in the SOBDA Score by Physician-completed mMRC and Participant-completed mMRC Responses at Visit 3/PD Ph-C mMRC, responders, n=91	-0.13 Scores on a scale Standard Deviation 0.416
Change From Baseline to Last Treatment Week in the SOBDA Score by Physician-completed mMRC and Participant-completed mMRC Responses at Visit 3/PD Ph-C mMRC, non-responders, n=210	-0.11 Scores on a scale Standard Deviation 0.472
Change From Baseline to Last Treatment Week in the SOBDA Score by Physician-completed mMRC and Participant-completed mMRC Responses at Visit 3/PD Pa-C mMRC, responders, n=92	-0.18 Scores on a scale Standard Deviation 0.508

PRIMARY outcome

Timeframe: Baseline (last week of the 2-week Run-in Period) and Weeks 1, 2, 3, 4, 5, and 6 (6-week Treatment Period)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation . The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

Changes from Baseline in the SOBDA score for responders (Rs) and non-responders (NRs) (using the PGAC assessment; 1 [much worse] to 5 [much better]), together with the cumulative proportions of Rs and NRs, was used to establish the threshold for defining SOBDA questionnaire Rs. The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on PGAC scores pre-specified as "better" or demonstrating meaningful improvement.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=97 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better" Week 5 to Week 6, n=26	-0.05 scores on a scale Standard Deviation 0.181
SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better" Baseline to Week 1, n=97	-0.26 scores on a scale Standard Deviation 0.325
SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better" Week 1 to Week 2, n=82	-0.08 scores on a scale Standard Deviation 0.219
SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better" Week 2 to Week 3, n=70	-0.08 scores on a scale Standard Deviation 0.216
SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better" Week 3 to Week 4, n=49	-0.10 scores on a scale Standard Deviation 0.216
SOBDA Threshold for Response Assessed as Mean Change From the Previous Week's SOBDA Score Based on a Participant-completed PGAC Score Rated of "Better" Week 4 to Week 5, n=66	-0.08 scores on a scale Standard Deviation 0.255

PRIMARY outcome

Timeframe: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on CGI-C scores pre-specified as "better" or demonstrating meaningful improvement. The CGI-C is clinician completed on a 1 to 5 scale: 1, much worse, 2, worse; 3, no change; 4, better; 5, much better.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=109 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
SOBDA Threshold for Response as Assessed by Mean Change From Baseline to the Last Treatment Week in the SOBDA Score Based on a CGI-C Response Rated as "Better"	-0.25 Scores on a scale Standard Deviation 0.484

PRIMARY outcome

Timeframe: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

The threshold of response (TOR) is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit. The TOR was evaluated as the change from Baseline in the SOBDA score based on CRQ-SAS scores pre-specified as "better" or demonstrating meaningful improvement. The CRQ-SAS DD includes 5 questions (q.) scored 1 (maximum impairment) to 7 (no impairment). Individual q. were equally weighted, and domain scores (DSs) (range=1-7) were calculated as the mean across the non-missing items within each domain (DSs were calculated although an individual item score was missing).

Outcome measures

Measure	All Participants: 2-week Run-in Period n=68 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
SOBDA Threshold for Response as Assessed by Mean Change From Baseline to the Last Treatment Week in the SOBDA Score Based on a CRQ-SAS Dyspnea Domain (DD) Response Rated as "Better"	-0.13 Scores on a scale Standard Deviation 0.417

PRIMARY outcome

Timeframe: Baseline and Week Prior to Visit 3/PD (end of 6-week Treatment Period or earlier up to Week 8)

Population: MITT Population. Analyses were conducted on data available for each specified time point. As pre-specified in the study protocol, results are presented independent of treatment allocation. The study objectives were to assess the measurement properties and validity of the SOBDA questionnaire independent of specific treatment effect.

FEV1 response was rated as 1=No change or worse (i.e., change of <50 mL); 2=Better (i.e., change of 50 to <100 mL); 3=Much better (i.e., change of >=100 mL). The threshold of response is a score change in the SOBDA questionnaire that is demonstrated to have a perceivable benefit for the participant. The threshold of response was evaluated as the change from Baseline in the SOBDA score based on study assessment (FEV1) scores pre-specified as "better" or demonstrating meaningful improvement.

Outcome measures

Measure	All Participants: 2-week Run-in Period n=42 Participants All participants in the 2-week Run-in Period. Participants were permitted to use albuterol and/or ipratropium as rescue medication during this period.
SOBDA Threshold for Response Assessed as Mean Change From Baseline to Last Treatment Week in the SOBDA Score Based on Forced Expiratory Volume in One Second (FEV1) Change From Baseline of 50 Milliliters (mL) to <100 mL	-0.16 mL Standard Deviation 0.492

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

SAL 50 mcg

Serious events: 5 serious events

Other events: 34 other events

Deaths: 0 deaths

FSC 250/50 mcg

Serious events: 3 serious events

Other events: 37 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=75 participants at risk Matching placebo via DISKUS, administered as one inhalation twice daily (BID)	SAL 50 mcg n=151 participants at risk Salmeterol xinafoate (SAL) 50 micrograms (mcg) per inhalation via DISKUS, administered as one inhalation BID	FSC 250/50 mcg n=139 participants at risk Fluticasone propionate and salmeterol xinafoate fixed dose combination product (FSC) 250/50 mcg per inhalation via DISKUS, administered as one inhalation BID during the 6-week Double-blind Treatment Period
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	5.3% 4/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.3% 2/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Cardiac disorders Myocardial Infarction	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Impaired Gastric Emptying	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
General disorders Chest Pain	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Pneumonia	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Metabolism and nutrition disorders Diabetes Mellitus Inadequate Control	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Nervous system disorders Cerebrovascular Accident	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Psychiatric disorders Suicide Attempt	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.

Other adverse events

Measure	Placebo n=75 participants at risk Matching placebo via DISKUS, administered as one inhalation twice daily (BID)	SAL 50 mcg n=151 participants at risk Salmeterol xinafoate (SAL) 50 micrograms (mcg) per inhalation via DISKUS, administered as one inhalation BID	FSC 250/50 mcg n=139 participants at risk Fluticasone propionate and salmeterol xinafoate fixed dose combination product (FSC) 250/50 mcg per inhalation via DISKUS, administered as one inhalation BID during the 6-week Double-blind Treatment Period
Gastrointestinal disorders Lip Swelling	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	5.3% 4/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	2.0% 3/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.7% 2/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	2.6% 4/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	2.0% 3/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.4% 2/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	2.0% 3/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Sinus Congestion	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.4% 2/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Respiratory Tract Congestion	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.3% 2/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Rhinitis Allergic	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Respiratory, thoracic and mediastinal disorders Rhinorrhea	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Candidiasis	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	2.2% 3/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Nasopharyngitis	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.3% 2/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Bronchitis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Gastroenteritis Viral	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Influenza	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Pneumonia	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.3% 2/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Respiratory Tract Infection	2.7% 2/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Acute Sinusitis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Gastric Infection	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Pharyngitis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Pneumonia Klebsiella	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Sinusitis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Tracheobronchitis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Infections and infestations Viral Upper Respiratory Tract Infection	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Nervous system disorders Headache	2.7% 2/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	4.0% 6/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	3.6% 5/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Nervous system disorders Sinus Headache	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	2.2% 3/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Nervous system disorders Carpal tunnel Syndrome	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Nervous system disorders Cerebrovascular Accident	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Nervous system disorders Dizziness	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Nervous system disorders Sciatica	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Nervous system disorders Syncope	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Nausea	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.3% 2/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Vomiting	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.3% 2/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Diarrhea	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Dyspepsia	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Abdominal Discomfort	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Constipation	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Dry mouth	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Impaired Gastric Emptying	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Melaena	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Stomatitis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Gastrointestinal disorders Toothache	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Myalgia	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.4% 2/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Pain In Extremity	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.4% 2/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Fibromyalgia	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Joint Swelling	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Lower Extremity Mass	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Muscle Spasms	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
General disorders Chest Pain	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	2.0% 3/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
General disorders Adverse Drug Reaction	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
General disorders Fatigue	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
General disorders Irritability	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
General disorders Edema Peripheral	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
General disorders Pain	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
General disorders Ankle Fracture	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Injury, poisoning and procedural complications Epicondylitis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Injury, poisoning and procedural complications Joint Sprain	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Injury, poisoning and procedural complications Muscle Strain	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Metabolism and nutrition disorders Hyperglycemia	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Metabolism and nutrition disorders Hyperlipidemia	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.3% 2/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Metabolism and nutrition disorders Diabetes Mellitus Inadequate Control	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Metabolism and nutrition disorders Gout	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Psychiatric disorders Anxiety	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	1.3% 2/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Psychiatric disorders Insomnia	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Psychiatric disorders Depression	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Psychiatric disorders Nervousness	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Psychiatric disorders Suicide Attempt	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Investigations Blood Pressure Increased	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Investigations Heart Rate Increased	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic Keratosis	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.66% 1/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Skin and subcutaneous tissue disorders Periorbital Edema	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Skin and subcutaneous tissue disorders Skin Lesion	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Blood and lymphatic system disorders Leukocytosis	1.3% 1/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Cardiac disorders Myocardial Infarction	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Ear and labyrinth disorders Ear Pain	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Eye disorders Vision Blurred	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Immune system disorders Multiple Allergies	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.
Vascular disorders Hypertension	0.00% 0/75 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.00% 0/151 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.	0.72% 1/139 Safety data are presented for the Modified Intent-to-Treat (MITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication. Data summaries and analyses were based on the actual treatment received. One participant in the SAL 50 mcg arm was randomized but did not receive treatment.

Additional Information

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