An Investigation Of The Interaction Of GSK961081 With Inh... | NCT00674817

Name	Class
GlaxoSmithKline	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
400 microgrammes GSK961081 and salbutamol	Experimental	400 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3x 200 microgrammes at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.	Drug: 400 microgrammes GSK961081
1200 microgrammes GSK961081 and salbutamol	Experimental	1200 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 microgrammes at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.	Drug: 400 microgrammes GSK961081 Drug: 1200 microgrammes GSK961081
400 microgrammes GSK961081 and ipratropium bromide	Experimental	400 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 microgrammes, 20 microgrammes and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.	Drug: 1200 microgrammes GSK961081
1200 microgrammes of GSK961081 and ipratropium bromide	Experimental	1200 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 microgrammes, 20 microgrammes and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.	Drug: 400 microgrammes GSK961081

Interventions

Name	Type	Description	Arm Group Labels	Other Names
400 microgrammes GSK961081	Drug	Inhaled GSK961081 administered via Dry Powder Inhaler.	1200 microgrammes GSK961081 and salbutamol 1200 microgrammes of GSK961081 and ipratropium bromide

Measure	Description	Time Frame
Maximal Change in Forced Expiratory Volume in One Second (FEV1) From Baseline (Pre-dose on Day 1) in Combination With Short Acting Bronchodialator (Salbutamol or Ipratropium Bromide) at 1h,12h and 24h.	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second as measured by spirometry. Adjusted mean has been presented as least square (LS) mean.	Baseline (pre-dose on Day 1), 1h, 12h, and 24h on Day 1

Measure	Description	Time Frame
Maximal Change in Forced Vital Capacity (FVC) in One Second From Pre-dose in Combination With Short Acting Bronchodialator (Salbutamol or Ipratropium Bromide) at 1h, 12h and 24h.	FVC is defined as the amount of air that can be forcibly exhaled from the lungs after a maximum inspiration as measured by spirometry. Adjusted mean has been presented as least square (LS) mean.	Baseline (Pre-dose on Day 1), 1h, 12h, and 24h on Day 1

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject is male or female (of non-child bearing potential) ≥ 40 years of age and ≤ 75 years of age.
Non- child bearing potential is defined as physiologically incapable of becoming pregnant, including females who are post-menopausal (more than 2 years without menses with appropriate clinical history i.e. age, history of vasomotor symptoms-estradiol and FSH levels may be checked if indicated) and females who are surgically sterile (hysterectomy, tubal ligation or bilateral oophorectomy).
Subject diagnosed with COPD in accordance with ATS/ERS guidelines (as per protocol).
Subject is a smoker or an ex-smoker with a history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent)
Subject has FEV1/FVC < 0.7 post-bronchodilator (salbutamol)
Subject has FEV1 < 80 % of predicted normal for height, age, gender after inhalation of salbutamol
Response to ipatropium bromide defined as:
Either an increase in FEV1 of > 12 % and > 150 mL within 2 hours following inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening visit
Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hours following inhalation of 80 µg ipratopium bromide within 6 months of screening and an increase in FEV1 of > 6 % and > 100 mL within 2h following inhalation of 80 µg ipratopium bromide (Atrovent MDI via spacer) at the screening visit (in order to allow for potential fluctuations in the response to ipratropium bromide in patients known to be responders to ipratropium bromide)
Response to salbutamol defined as:
Either an increase in FEV1 of > 12 % and > 150 mL within 2 hours following inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit
Or: a documented increase in FEV1 of >12 % and > 150 mL within 2 hours following inhalation of 400 µg salbutamol MDI within 6 months of screening and an increase in FEV1 of > 6 % and >100 mL within 2h following inhalation of 400 µg salbutamol MDI (via spacer) at the screening visit (in order to allow for potential fluctuations in the response to salbutamol in patients known to be responders to salbutamol)
Body mass index (BMI) within the range 18-35 kg/m2
Subject is able and willing to give written informed consent to take part in the study.
Subject is available to complete all study assessments

Exclusion Criteria:

Subjects who have a past or present disease, which as judged by the Investigator and medical monitor may affect the outcome of the study or the safety of the subject
Subjects with clinically relevant findings on laboratory safety tests. Subjects with laboratory values outside the reference range may be include in the study if the Investigator and medical monitor agree that these findings would not put the subject at risk or interfere with the objectives of the study
Women who are pregnant or lactating
An unwillingness of subjects to abstain from sexual intercourse with pregnant or lactating women; or an unwillingness of the subject to use a condom/spermicide in addition to having their female partner use another form of contraception such as IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, subdermal implants or tubal ligation if the woman could become pregnant from the time of the first dose study medication until 90 days post-dose
The subject has a positive urine drugs of abuse screen. A minimum list of drugs that will be screened for include amphetamines, barbituates, cocaine, opiates, cannabinoids and benzodiazepines.
A history, or suspected history, of alcohol abuse within the 6 months before the screening visit.
A positive test for hepatitis C antibody, hepatitis B surface antigen, or HIV.
The subject has participated in a clinical study with another New Chemical Entity within the past 2 months or participated in a clinical study with any other drug during the previous month.
The subject has donated a unit of blood within the 56 days of dosing or intends to donate within 56 days after completing the study.
Subject has an FEV1 < 40 % of predicted for age, height and gender after inhalation of salbutamol.
The subject has a diagnosis of active tuberculosis, lung cancer, sarcoidosis, bronchiectasis, lung fibrosis, pulmonary hypertension or with a primary diagnosis of asthma
The subject has a known allergy or hypersensitivity to ipratropium bromide, salbutamol, or lactose
A subject in whom ipratropium bromide or salbutamol is contraindicated
Subjects with lung volume reduction surgery within 12 months of screening
Poorly controlled COPD defined as:
Either: acute worsening of COPD that is managed by the subject at home by treatment with increased corticosteroids or antibiotics in the 6 weeks before screening
Or: more than 2 exacerbations in the previous 12 months before screening that required a course of oral steroids or antibiotics, and/or required hospitalisation
Subject has had a respiratory tract infection in the 4 weeks before screening
Subject requires treatment with inhaled cromolyn sodium, theophyline, oral ß2- agonists, nebulised anticholinergics or leukotriene antagonists
Subject is unable to abstain from long acting ß2-agonist from 72 hours before screening and throughout the dosing period
Subject is unable to abstain from tiotropium bromide from 28 days before screening and throughout the dosing period
Subject is predicted to be unable to abstain from short acting inhaled ß2-agonists or short acting antimuscarinics for 6 hours before screening and for 6 hours before dosing with GSK961081 until all post-dose lung function tests have been completed for a given study day.
Subject has received oral corticosteroids within the 6 weeks before screening
Subject is receiving > 1000 µg FP (or equivalent) a day of inhaled corticosteroid or has changed dose within the 6 weeks before screening or is predicted not to be able to maintain a constant dose during the study
Subject is receiving oxygen therapy or nocturnal positive pressure treatment
Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholinergic
The subject is unable to use the dosing devices (MDPI/ MDI/ spacer) correctly.
Subject with carcinoma that has not been in complete remission for at least 5 years (with the exception of carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma if the subject is considered cured)
A history of congestive heart failure, coronary insufficiency or cardiac arrhythmia or a finding on screening 24h Holter monitor that would contraindicate the subject's participation in the study
12- lead ECG abnormality which is either clinically significant or may interfere with QTc measurement or QTc > 450 msec or PR interval outside the range 120 to 220 msec.
A supine mean heart rate outside the range 40-90 bpm at screening.
Persistently elevated supine blood pressure higher than 160/95 at screening.
Subject is receiving a high-dose diuretic and/ or ß2-adrenergic antagonist
Subject has a serum potassium level below the reference range at screening.
Inability to understand the protocol requirements, instructions and study-related restrictions; the nature, scope and possible consequences of the study.
Unlikely to complete the study; e.g., uncooperative attitude, inability to return for follow-up visits.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Wellington		6035	New Zealand
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
23524017	Background	Norris V, Ambery C. Bronchodilation and safety of supratherapeutic doses of salbutamol or ipratropium bromide added to single dose GSK961081 in patients with moderate to severe COPD. Pulm Pharmacol Ther. 2013 Oct;26(5):574-80. doi: 10.1016/j.pupt.2013.03.009. Epub 2013 Mar 21.

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
MAB110123	Informed Consent Form	View IPD

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Total Population	Eligible participants received GSK961981 400 micrograms (mcg) and 1200 mcg metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3x 200 mcg at 0 min intervals, administered via spacer) of salbutamol at 1hour (h), 12h and 24h of dosing during first and second treatment periods, respectively. Eligible participants received GSK961981 400 mcg and 1200 mcg followed by cumulative doses (20 mcg , 20 mcg and 40 mcg at 20 minutes intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing during third and forth treatment period, respectively. Eligible participants received GSK961981 400 mcg and 1200 mcg followed by cumulative doses (3 doses at 20 minutes intervals, administered via spacer) of Placebo at 1h, 12h and 24h of dosing during fifth and sixth treatment period, respectively.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Maximal Change in Forced Expiratory Volume in One Second (FEV1) From Baseline (Pre-dose on Day 1) in Combination With Short Acting Bronchodialator (Salbutamol or Ipratropium Bromide) at 1h,12h and 24h.

FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second as measured by spirometry. Adjusted mean has been presented as least square (LS) mean.

Modified per protocol population included the participants who received at least one dose of the study drug where major deviations from the protocol had not occurred. Only those participants available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Liters

Baseline (pre-dose on Day 1), 1h, 12h, and 24h on Day 1

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.
OG003	GSK961081 1200 mg Plus IPR	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg, and 40 mcg at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.
OG004	GSK961081 400 mg Plus Placebo	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3 doses at 20 min intervals, administered via spacer) of placebo at 1h, 12h and 24h of dosing.
OG005	GSK961081 1200 mg Plus Placebo	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3 doses at 20 min intervals, administered via spacer) of placebo at 1h, 12h and 24h of dosing.

Units	Counts
Participants	OG00039 OG00141 OG00241 OG003

Title	Denominators	Categories
1 hour	ParticipantsOG00039 ParticipantsOG00141 ParticipantsOG00240 ParticipantsOG003

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 OG004	GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo' at 1 hour	Mix model		=0.020		Mean Difference (Final Values)	0.039	Standard Error of the Mean	0.0187	2-Sided	90	0.008	0.069					Superiority or Other (legacy)
OG000 OG004	GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo at 12 hour

Secondary

Maximal Change in Forced Vital Capacity (FVC) in One Second From Pre-dose in Combination With Short Acting Bronchodialator (Salbutamol or Ipratropium Bromide) at 1h, 12h and 24h.

FVC is defined as the amount of air that can be forcibly exhaled from the lungs after a maximum inspiration as measured by spirometry. Adjusted mean has been presented as least square (LS) mean.

Modified per protocol population. Only those participants available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Liters

Baseline (Pre-dose on Day 1), 1h, 12h, and 24h on Day 1

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Number of Participants With Adverse Events and Serious Adverse Events

An adverse event (AE) is any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious AE (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.

All subjects population

Posted

Number

Participants

Upto 82 days

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)

The normal ranges of laboratory parameters were hemoglobin: 130-167 grams per deciliter (g/dL), platelets: 173-383 Giga per liter (GI/L), lymphocytes: 20.1-44.5 %, glucose: 3.8857-6.106 millimoles per liter (mmol/L), creatinine: 44.2-132.6 micromoles per liter (uM/L) , aspartate transaminases (AST): 12-32 international units per liter (IU/L), total bilirubin (TB): 4.275-25.65 uM/L and potassium: 3.4-4.7 mmol/L, respectively. Laboratory values recorded outside the normal range were considered of potential clinical concern (PCC).

All subjects population

Posted

Number

Participants

Up to 42 days

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR

Secondary

Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours

Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was analyzed. Change from baseline is the difference in the blood pressure at the indicated time point minus the Baseline value.

All subjects population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Millimeters of mercury (mm of Hg)

Up to 27 hours post Day 1 dosing

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours

Heart rate was considered as a measure of vital sign. Change from baseline is the difference in the blood pressure at the indicated time point minus the Baseline value.

All subjects population. Only those participants available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Beats per minute

Up to 27 hours post Day 1 dosing

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings

Analysis QTc interval of ECG was performed by Bazett's formula (QTc B) and Fridericia's correction (QTc F). Number of participants with abnormal ECG findings were recorded. Any participant with QTc(B) or QTc(F) >500 milliseconds (msec) or uncorrected QT >600 msec (machine or manual over read) was withdrawn from the study. Participants that had right bundle branch block with QTc(B) or QTc(F) >530 msec were also withdrawn from the study.

All subjects population

Posted

Number

Participants

From dosing until 24h post-dose.

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing

Analysis of QT (F) interval during ECG (taken in supine position) was performed using Fridericia's method. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted means are considered as least square (LS) mean values while presenting the data.

Modified per protocol population

Posted

Mean

Standard Deviation

msec

From dosing until 4 hours (0-4h)

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing

Analysis of Q T (F) interval during ECG (taken in supine position) was performed using Fridericia's method. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted means are considered as LS mean values while presenting the data .

Modified per protocol population

Posted

Mean

Standard Deviation

msec

From dosing until 27 hours (0-27h)

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours

Analysis of QT(F) interval during ECG (taken in supine position) was performed using Fridericia's method. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.

Modified per protocol population. Only those participants available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Deviation

msec

From dosing until 4 hours (0-4h)

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Maximum Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours and 0 to 27 Hours

Analysis of QT (B) interval during ECG (taken in supine position) was performed using Bazett's method. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data .

Modified Per Protocol population.

Posted

Least Squares Mean

Standard Error

msec

From dosing until 4 hours (0-4h) and 27 hours (0-27h)

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours

Modified Per Protocol population.

Posted

Least Squares Mean

Standard Error

msec

From dosing until 4 hours (0-4h)

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.

Heart rate was measured in supine position. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted means are considered as LS mean values while presenting the data.

Modified Per Protocol population.

Posted

Least Squares Mean

Standard Error

Beats per minute

From dosing until 4 hours (0-4h) and until 27 hours (0-27 h)

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours

Heart rate was recorded in supine position. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.

Modified Per Protocol population. Data is presented for the participants available at the time of assessment.

Posted

Least Squares Mean

Standard Error

Beats per minute

From dosing until 4 hours (0-4h)

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Maximum Change From Baseline (Pre-dose on Day 1) in Supine Systolic Blood Pressure (SBP) Over 4 and 27 Hours and Weighted Mean Change From Baseline in Supine SBP Over 4 Hours

Systolic blood pressure (SBP) values were recorded in supine position. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted or maximum change/ (MC) and weighted mean change (WMC) are considered as LS mean change values while presenting the data.

Modified Per Protocol population. Only those participants available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Millimeters of mercury

0-4h and 0-27h for maximum change and 0-4 h for weighted mean change

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR

Secondary

Minimum Change From Baseline (Pre-dose on Day 1) in Supine Diastolic Blood Pressure (DBP) Over 4 and 27 Hours and Weighted Mean Change From Baseline in Supine DBP Over 4 Hours

Diastolic blood pressure (DBP) values were recorded in supine position. Change from baseline is the value at indicated time point minus the value at Baseline. Adjusted or maximum change/(MC) and weighted mean change (WMC) are considered as LS mean change values while presenting the data .

Modified Per Protocol population. Only those participants available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Millimeters of mercury

0-4h and 0-27h for maximum change and 0-4 h for weighted mean change

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR

Secondary

Maximum Change From Baseline (Pre-dose on Day 1) in Glucose Over 4 and 27 Hours and Weighted Mean Change From Baseline in Glucose Over 4 Hours

Maximum change (MC) from Baseline (BL) and weighted mean change (WMC) from baseline in glucose (GLU) were analyzed. Change from Baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.

Modified Per Protocol population. Only those participants available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Millimoles per Liter

0-4h and 0-27h for maximum change and 0-4 h for weighted mean change

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR

Secondary

Minimum Change From Baseline (Pre-dose on Day 1) in Potassium Over 4 and 27 Hours and Weighted Mean Change From Baseline in Potassium Over 4 Hours

Maximum change (MC) from Baseline (BL) and weighted mean change (WMC) from baseline in potassium (K) were analyzed. Change from Baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.

Modified Per Protocol population. Only those participants available at the specified time points were analyzed.

Posted

Least Squares Mean

Standard Error

Millimoles per Liter

0-4h and 0-27h for maximum change and 0-4 h for weighted mean change

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR

Secondary

Time to Maximum Change From Baseline (Pre-dose on Day 1) for QTc(B), QTc(F), Heart Rate, Systolic BP, Glucose in Supine Position and Time to Minimum Change From Baseline for Potassium and Diastolic BP in Supine Position

Analysis of QT (B) or QTc (F) interval during ECG (taken in supine position) was performed using Bazett's method and Fridericia's method, respectively. Heart rate, BP, potassium, and glucose were measured in supine body position. Change from baseline is the value at indicated time point minus the value at Baseline. Weighted means are considered as LS mean values while presenting the data.

Modified Per Protocol population. n=data is presented for the participants available at the time of assessment.

Posted

Median

Full Range

hours

From dosing until 4 hours (0-4h)

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002

Secondary

Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration

AUC(0-t) is the area under plasma concentration time curve of GSK961081 to the last quantifiable concentration. This parameter was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. A large proportion of AUC(0-t) and Cmax values were reported as not countable (NC) at the GSK961081 400 micrograms (ug) dose level, therefore only limited summaries were calculated. Logarithmic transformed values are presented. AUC(0-t) imputed with 1/2 lowest observed AUC(0-t), where lowest AUC(0-t) was 56.46 hour picograms per milliliter (h*pg/mL).

Pharmacokinetic (PK) population included participants in the 'All Subjects' population for whom a PK sample was obtained and analyzed following GSK961081 dosing. All participants were available at the time of analysis; however, for few participants, parameter cannot be derived because of non-quantifiable concentrations.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*pg/mL

Up to 82 days

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.

Secondary

Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data

Cmax is the Maximum observed concentration of GSK961081 determined directly from the concentration-time data. A large proportion of Cmax values were reported as not countable (NC ) at the GSK961081 400 micrograms (ug) dose level, therefore only limited summaries were calculated. Logarithmic transformed values are presented. Cmax was imputed with 1/2 lowest limit of quantification (LLQ), where LLQ was 25 picograms per milliliter (pg/mL).

PK population. All participants were present for analysis, however, there were few participants for whom parameter could not be derived because of non-quantifiable concentrations.

Posted

Geometric Mean

Geometric Coefficient of Variation

pg/mL

Up to 82 days

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002

Secondary

Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data

Tmax is the time to maximum plasma concentration of GSK961081 over period determined directly from the concentration-time data

PK population. All participants were present for the analysis; however, there were few participants for whom parameter could not be derived because of non-quantifiable concentrations. Data is presented for the participants available at the time of assessment.

Posted

Median

Full Range

Hours

Up to 82 days

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Secondary

Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data

Tlast is the time to last quantifiable plasma concentration of GSK961081 over period determined directly from the concentration-time data

PK population. All participants were present for the analysis; however, there were few participants for whom parameter could not be derived because of non-quantifiable concentration. Data is presented for the participants available at the time of assessment.

Posted

Median

Full Range

hours

Up to 82 days

ID	Title	Description
OG000	GSK961081 400 mg Plus SAL	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG001	GSK961081 1200 mg Plus SAL	Eligible participants received 1200 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 mcg at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.
OG002	GSK961081 400 mg Plus IPR	Eligible participants received 400 mcg of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 mcg, 20 mcg and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	400 Microgrammes GSK961081 and Salbutamol	400 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3x 200 microgrammes at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.	0	39	13	39
EG001	1200 Microgrammes GSK961081 and Salbutamol	1200 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (3x 200 microgrammes at 20 min intervals, administered via spacer) of salbutamol at 1h, 12h and 24h of dosing.	1	41	13	41
EG002	400 Microgrammes GSK961081 and Ipratropium Bromide	400 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 microgrammes, 20 microgrammes and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.	1	41	14	41
EG003	1200 Microgrammes of GSK961081 and Ipratropium Bromide	1200 microgrammes of GSK961081 single-dose (via DISKUS MDPI) followed by cumulative doses (20 microgrammes, 20 microgrammes and 40 microgrammes at 20 min intervals, administered via spacer) of ipratropium bromide at 1h, 12h and 24h of dosing.	0	41	9	41
EG004	400 Microgrammes of GSK961081 and Placebo	400 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3 doses at 20 min intervals, administered via spacer) of placebo at 1h, 12h and 24h of dosing.	0	40	6	40
EG005	1200 Microgrammes of GSK961081 and Placebo	1200 microgrammes of GSK961081 single-dose (via DISKUS Metered Dry Powder Inhaler/ MDPI) followed by cumulative doses (3 doses at 20 min intervals, administered via spacer) of placebo at 1h, 12h and 24h of dosing.	0	39	11	39

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA	Systematic Assessment	EG0005 affected39 at risk EG0015 affected41 at risk EG0024 affected41 at risk EG0034 affected41 at risk EG0041 affected40 at risk EG0053 affected39 at risk
Dysgeusia	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0011 affected41 at risk EG0020 affected41 at risk EG003
Tremor	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0012 affected41 at risk EG0021 affected41 at risk EG003
Dizziness	Nervous system disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0011 affected41 at risk EG0020 affected41 at risk EG003
Syncope	Nervous system disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0011 affected41 at risk EG0020 affected41 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0011 affected41 at risk EG0021 affected41 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0021 affected41 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0021 affected41 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0011 affected41 at risk EG0022 affected41 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0021 affected41 at risk EG003
Bursitis infective	Infections and infestations	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0011 affected41 at risk EG0020 affected41 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0013 affected41 at risk EG0020 affected41 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Gout	Metabolism and nutrition disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0021 affected41 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Animal scratch	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Epicondylitis	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Joint sprain	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0021 affected41 at risk EG003
Medical device complication	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Rib fracture	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0011 affected41 at risk EG0020 affected41 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0011 affected41 at risk EG0023 affected41 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Application site erythema	General disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Application site rash	General disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Application site vesicles	General disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0021 affected41 at risk EG003
Asthenia	General disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Catheter site pain	General disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0002 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Palpitations	Cardiac disorders	MedDRA	Systematic Assessment	EG0001 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Seasonal allergy	Immune system disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0011 affected41 at risk EG0020 affected41 at risk EG003
Anxiety	Psychiatric disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003
Hypertension	Vascular disorders	MedDRA	Systematic Assessment	EG0000 affected39 at risk EG0010 affected41 at risk EG0020 affected41 at risk EG003

ID	Term
D029424	Pulmonary Disease, Chronic Obstructive
D001249	Asthma

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D001982	Bronchial Diseases
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Angina pectoris	Cardiac disorders	MedDRA	Systematic Assessment		EG0000 affected39 at risk EG0010 affected41 at risk EG0021 affected41 at risk EG0030 affected41 at risk EG0040 affected40 at risk EG0050 affected39 at risk
Migraine with aura	Nervous system disorders	MedDRA	Systematic Assessment		EG0000 affected39 at risk EG0011 affected41 at risk EG0020 affected41 at risk EG003