Asthma Clinical Research Network (ACRN) Trial - Long-Acti... | NCT00200967

Asthma Clinical Research Network (ACRN) Trial - Long-Acti... | NCT00200967 | Trialant

Secondary IDs

ID	Type	Link
5U10HL074231	U.S. NIH Grant/Contract	View source
U10HL074073	U.S. NIH Grant/Contract	View source
U10HL074204	U.S. NIH Grant/Contract	View source
U10HL074208	U.S. NIH Grant/Contract	View source
U10HL074212	U.S. NIH Grant/Contract	View source
U10HL074218	U.S. NIH Grant/Contract	View source
U10HL074225	U.S. NIH Grant/Contract	View source
U10HL074227	U.S. NIH Grant/Contract	View source
U10HL074231	U.S. NIH Grant/Contract	View source

Sponsor/Collaborators Module

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
Asthma Clinical Research Network	NETWORK

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
B16 Arg/Arg	Experimental	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone hydroflouroalkane (HFA), followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA	Drug: salmeterol Drug: beclomethasone HFA
B16 Gly/Gly	Experimental	B16 Gly/Gly genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA	Drug: salmeterol Drug: beclomethasone HFA

Name	Type	Description	Arm Group Labels	Other Names
salmeterol	Drug	50 micrograms (mcg) twice per day (BID) (Serevent 50 mcg diskus, GlaxoSmithKline (GSK), North Carolina)	B16 Arg/Arg B16 Gly/Gly

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Morning (AM) Peak Expiratory Flow (PEF) Rate	Change between placebo salmeterol and active salmeterol for AM PEF rate	Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

Secondary Outcomes

Measure	Description	Time Frame
Evening (PM) Peak Expiratory Flow (PEF) Rate	Change between placebo salmeterol and active salmeterol for PM PEF rate	Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period
Peak Expiratory Flow (PEF) Variability

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Homer Boushey	University of California, San Francisco	Principal Investigator
Mario Castro	Washington University School of Medicine	Principal Investigator
Vernon M. Chinchilli, PhD	Milton S. Hershey Medical Center	Principal Investigator
Elliot Israel	Brigham and Women's Hospital	Principal Investigator
Robert Lemanske	University of Wisconsin, Madison	Principal Investigator
Richard Martin	National Jewish Medical & Research Center	Principal Investigator
Stephen Peters	Wake Forest University Health Sciences	Principal Investigator
Stephen Wasserman	University of California, San Diego	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of California, San Diego		San Diego	California	92103	United States
University of California, San Francisco

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
19932356	Result	Wechsler ME, Kunselman SJ, Chinchilli VM, Bleecker E, Boushey HA, Calhoun WJ, Ameredes BT, Castro M, Craig TJ, Denlinger L, Fahy JV, Jarjour N, Kazani S, Kim S, Kraft M, Lazarus SC, Lemanske RF Jr, Markezich A, Martin RJ, Permaul P, Peters SP, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Walter MJ, Wasserman SI, Israel E; National Heart, Lung and Blood Institute's Asthma Clinical Research Network. Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet. 2009 Nov 21;374(9703):1754-64. doi: 10.1016/S0140-6736(09)61492-6.

Label	URL
Asthma Clinical Research Network (ACRN) Website	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Wash-out Period

Type	Comment	Milestone Data
STARTED		FG00036 subjects FG00144 subjects
COMPLETED		FG00036 subjects FG00143 subjects
NOT COMPLETED		FG0000 subjects FG0011 subjects

Type	Comment	Reasons
Lost to Follow-up		FG0000 subjects FG0011 subjects

Second Treatment Period

Type	Comment	Milestone Data
STARTED		FG00036 subjects FG00143 subjects
COMPLETED		FG00035 subjects FG00141 subjects
NOT COMPLETED		FG0001 subjects FG0012 subjects

Type	Comment	Reasons
Withdrawal by Subject		FG0001 subjects FG0012 subjects

Run-out Period

Type	Comment	Milestone Data
STARTED		FG00035 subjects FG00141 subjects
COMPLETED		FG00034 subjects FG00141 subjects
NOT COMPLETED		FG0001 subjects FG0010 subjects

Type	Comment	Reasons
Lost to Follow-up		FG0001 subjects FG0010 subjects

Arm/Group Information

ID	Title	Description
BG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
BG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00039± 11 BG00142± 12 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00032 BG00129 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00042 BG00145 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Morning (AM) Peak Expiratory Flow (PEF) Rate

Change between placebo salmeterol and active salmeterol for AM PEF rate

An intention-to-treat (ITT) paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Least Squares Mean

95% Confidence Interval

liters per minute

Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants	OG00042 OG00145

Title

Denominators

Categories

Title	Measurements
	OG000-21(-31 to -12) OG001-22(-32 to -11)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design. A sample size of 40 participants per genotype was required to detect a difference of 25 L/min in AM PEF (and relevant effect sizes for secondary outcomes) with a two-sided, 0.05 significance level test with 90% statistical power and a 15% drop-out rate.	Mixed Models Analysis		0.99		Mean Difference (Final Values)	0	Standard Error of the Mean	7		95	-14	14			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for AM PEF rate.

Secondary

Evening (PM) Peak Expiratory Flow (PEF) Rate

Change between placebo salmeterol and active salmeterol for PM PEF rate

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Least Squares Mean

95% Confidence Interval

liters per minute

Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Peak Expiratory Flow (PEF) Variability

Change between placebo salmeterol and active salmeterol for PEF variability, where PEF variability is defined as 100% x (PM PEF - AM PEF)/(PM PEF)

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Least Squares Mean

95% Confidence Interval

percentage

Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts

Secondary

Asthma Symptoms

Change between placebo salmeterol and active salmeterol for asthma symptoms (0=absent, 1=mild, 2=moderate, 3=severe).

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Mean

95% Confidence Interval

units on a scale

Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Rescue Medication (Ipratropium and Albuterol) Use

Change between placebo salmeterol and active salmeterol for rescue medication use

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Mean

95% Confidence Interval

puffs per day

Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Spirometry Forced Expiratory Volume in One Second (FEV1), Pre-bronchodilator

Change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Least Squares Mean

95% Confidence Interval

liters

Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator

Change between placebo salmeterol and active salmeterol for Spirometry FVC, pre-bronchodilator

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Least Squares Mean

95% Confidence Interval

liters

Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Spirometry Peak Expiratory Flow (PEF) Rate, Pre-bronchodilator

Change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Least Squares Mean

95% Confidence Interval

liters per minute

Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Exhaled Nitric Oxide (eNO)

Change between placebo salmeterol and active salmeterol for eNO

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Geometric Mean

95% Confidence Interval

parts per billion

Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Exhaled Breath Condensate (EBC)

Change between placebo salmeterol and active salmeterol for EBC

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Least Squares Mean

95% Confidence Interval

Clinic visits at weeks 0, 10, and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Methacholine Provocative Concentration 20 (PC20)

Change between placebo salmeterol and active salmeterol for methacholine PC20

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Geometric Mean

95% Confidence Interval

milligrams per milliliter

Clinic visits at weeks 0 and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Secondary

Asthma Control Questionnaire (ACQ)

Change between placebo salmeterol and active salmeterol for ACQ, where ACQ ranges from 0 (best asthma control) to 6 (worst asthma control).

An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.

Posted

Least Squares Mean

95% Confidence Interval

units on a scale

Clinic visits at weeks 0 and 18 of each treatment period

ID	Title	Description
OG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA
OG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	B16 Arg/Arg	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA			1	42	20	42
EG001	B16 Gly/Gly	B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA			4	45	20	45

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
hospitalization	General disorders		Systematic Assessment		EG0000 events0 affected42 at risk EG0011 events1 affected45 at risk
hospitalization	Psychiatric disorders		Systematic Assessment		EG0001 events1 affected42 at risk EG0013 events3 affected45 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
respiratory infection	Respiratory, thoracic and mediastinal disorders		Systematic Assessment		EG000100 events20 affected42 at risk EG00198 events20 affected45 at risk

Ancestor Terms

ID	Term
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

Ancestor Terms

ID	Term
D000420	Albuterol
D004983	Ethanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D000588	Amines
D010627	Phenethylamines
D005021	Ethylamines
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013258	Steroids, Chlorinated

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.82		Mean Difference (Final Values)	-1	Standard Error of the Mean	7		95	-15	12			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for PM PEF rate.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.31		Mean Difference (Final Values)	-0.6	Standard Error of the Mean	0.5		95	-1.6	0.5			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for PEF variability.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was attempted but could not converge because very few symptoms were recorded, so a nonparametric analysis was applied.	Wilcoxon (Mann-Whitney)		0.09		Mean Difference (Final Values)	0.02	Standard Error of the Mean	0.02		95	-0.02	0.07			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for asthma symptoms.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was attempted but could not converge because very few usages of rescue medications were recorded, so a nonparametric analysis was applied.	Wilcoxon (Mann-Whitney)		0.25		Mean Difference (Final Values)	0.0	Standard Error of the Mean	0.1		95	-0.1	0.2			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for rescue medication use.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.34		Mean Difference (Final Values)	-0.03	Standard Error of the Mean	0.03		95	-0.10	0.03			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.91		Mean Difference (Final Values)	0.00	Standard Error of the Mean	0.03		95	-0.08	0.07			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for Spirometry FVC, pre-bronchodilator.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.93		Mean Difference (Final Values)	-1	Standard Error of the Mean	7		95	-15	14			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to the natural logarithm of eNO to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.13		Mean Difference (Final Values)	0.14	Standard Error of the Mean	0.08		95	-0.04	0.31			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for eNO.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.79		Mean Difference (Final Values)	-0.07	Standard Error of the Mean	0.24		95	-0.56	0.43			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for EBC.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to the base-2 logarithm of the methacholine PC20 to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.004		Mean Difference (Final Values)	1.32	Standard Error of the Mean	0.45		95	0.43	2.21			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for methacholine PC20.		Superiority or Other

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.	Mixed Models Analysis		0.89		Mean Difference (Final Values)	0.02	Standard Error of the Mean	0.12		95	-0.23	0.26			The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for ACQ.		Superiority or Other

ID	Term
D000068299	Salmeterol Xinafoate
D001507	Beclomethasone