An Investigation Of The Interaction Of GSK961081 With Inhaled Beta-Agonist And Anti-Muscarinic Drugs.

A Randomized, Double-blind, Crossover Study to Investigate the Bronchodilatation Post-inhalation of GSK961081 Alone and With the Addition of Cumulative Doses of Short Acting Bronchodilators (Salbutamol and Ipratropium Bromide) in Patients With COPD

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00674817

Enrollment

Registered

2008-05-08

Start date

2008-04-01

Completion date

2008-10-19

Last updated

2021-10-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

salbutamol,, Chronic Obstructive Pulmonary Disease (COPD), GSK961081 muscarinic receptor antagonist,, COPD, ipratropium bromide,, Asthma, ß2-adrenergic agonist,

Brief summary

GSK961081 is a potent dual pharmacophore that demonstrates both antimuscarinic and beta-agonist pharmacology in preclinical studies, both pharmacologies being of long duration. If reproduced in man, GSK961081 has the potential to deliver a medicine that can be given once daily. The bronchodilatation after inhalation of single doses of GSK961081 alone and in the presence of the short acting beta agonist salbutamol and the short acting muscarinic antagonist, ipratropium bromide will be measured in this study. Any residual bronchodilatation post-inhalation of GSK961081 and demonstrated by addition of salbutamol or ipratropium bromide may provide an indirect assessment of the beta-agonist and antimuscarinic components of GSK961081

Detailed description

Interventions

DRUG400 microgrammes GSK961081

Inhaled GSK961081 administered via Dry Powder Inhaler.

DRUG1200 microgrammes GSK961081

Inhaled GSK961081 adminisntered via dry powder inhaler.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

40 Years to 75 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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.	Baseline (pre-dose on Day 1), 1h, 12h, and 24h on Day 1	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.

Secondary

Measure	Time frame	Description
Number of Participants With Adverse Events and Serious Adverse Events	Upto 82 days	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.
Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Up to 42 days	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).
Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	Up to 27 hours post Day 1 dosing	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.
Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	Up to 27 hours post Day 1 dosing	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.
Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	From dosing until 24h post-dose.	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.
Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing	From dosing until 4 hours (0-4h)	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.
Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing	From dosing until 27 hours (0-27h)	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 .
Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours	From dosing until 4 hours (0-4h)	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.
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	From dosing until 4 hours (0-4h) and 27 hours (0-27h)	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 .
Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours	From dosing until 4 hours (0-4h)	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.
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.	Baseline (Pre-dose on Day 1), 1h, 12h, and 24h on Day 1	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.
Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours	From dosing until 4 hours (0-4h)	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.
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	0-4h and 0-27h for maximum change and 0-4 h for weighted mean change	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.
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	0-4h and 0-27h for maximum change and 0-4 h for weighted mean change	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 .
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	0-4h and 0-27h for maximum change and 0-4 h for weighted mean change	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.
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	0-4h and 0-27h for maximum change and 0-4 h for weighted mean change	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.
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	From dosing until 4 hours (0-4h)	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.
Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration	Up to 82 days	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).
Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	Up to 82 days	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).
Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	Up to 82 days	Tmax is the time to maximum plasma concentration of GSK961081 over period determined directly from the concentration-time data
Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data	Up to 82 days	Tlast is the time to last quantifiable plasma concentration of GSK961081 over period determined directly from the concentration-time data
Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	From dosing until 4 hours (0-4h) and until 27 hours (0-27 h)	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.

Countries

New Zealand, Thailand, United Kingdom

Participant flow

Recruitment details

This study was conducted from 25Apr2008 to 19Oct2008 across two centers in Thailand and one center each in the United Kingdom and New Zealand. A total of 45 participants were planned to be enrolled.

Pre-assignment details

A total of 44 participants were screened over period of 28 days and were enrolled in the study.

Participants by arm

Arm	Count
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.	44
Total	44

Arm

Count

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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Period 1	Protocol Violation	1
Period 1	Withdrawal by Subject	2
Period 3	Adverse Event	1
Period 3	Protocol Violation	1
Period 4	Adverse Event	1

Baseline characteristics

Characteristic	Total Population
Age, Continuous Years	63.1 Years STANDARD_DEVIATION 6.58
Race/Ethnicity, Customized Asian - South East Asian Heritage	22 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	1 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	21 Participants
Sex: Female, Male Female	8 Participants
Sex: Female, Male Male	36 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	13 / 39	13 / 41	14 / 41	9 / 41	6 / 40	11 / 39
serious Total, serious adverse events	0 / 39	1 / 41	1 / 41	0 / 41	0 / 40	0 / 39

Outcome results

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.

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

Population: 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.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	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.	12 hour	0.141 Liters	Standard Error 0.0173
GSK961081 400 mg Plus SAL	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.	24 hour	0.161 Liters	Standard Error 0.0166
GSK961081 400 mg Plus SAL	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.	1 hour	0.111 Liters	Standard Error 0.0146
GSK961081 1200 mg Plus SAL	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.	12 hour	0.134 Liters	Standard Error 0.017
GSK961081 1200 mg Plus SAL	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.	1 hour	0.113 Liters	Standard Error 0.0142
GSK961081 1200 mg Plus SAL	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.	24 hour	0.175 Liters	Standard Error 0.0163
GSK961081 400 mg Plus IPR	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.	24 hour	0.179 Liters	Standard Error 0.0162
GSK961081 400 mg Plus IPR	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.	1 hour	0.087 Liters	Standard Error 0.0144
GSK961081 400 mg Plus IPR	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.	12 hour	0.127 Liters	Standard Error 0.017
GSK961081 1200 mg Plus IPR	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.	1 hour	0.111 Liters	Standard Error 0.0144
GSK961081 1200 mg Plus IPR	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.	12 hour	0.098 Liters	Standard Error 0.0171
GSK961081 1200 mg Plus IPR	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.	24 hour	0.172 Liters	Standard Error 0.0166
GSK961081 400 mg Plus Placebo	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.	12 hour	0.002 Liters	Standard Error 0.017
GSK961081 400 mg Plus Placebo	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.	1 hour	0.072 Liters	Standard Error 0.0144
GSK961081 400 mg Plus Placebo	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.	24 hour	0.039 Liters	Standard Error 0.0163
GSK961081 1200 mg Plus Placebo	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.	1 hour	0.094 Liters	Standard Error 0.0149
GSK961081 1200 mg Plus Placebo	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.	24 hour	0.049 Liters	Standard Error 0.0169
GSK961081 1200 mg Plus Placebo	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.	12 hour	0.043 Liters	Standard Error 0.0174

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo' at 1 hourp-value: =0.0290% CI: [0.008, 0.069]Mix model

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo at 12 hourp-value: <0.00190% CI: [0.101, 0.176]Mix model

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo at 24 hourp-value: <0.00190% CI: [0.087, 0.158]Mix model

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo at 1 hourp-value: =0.2290% CI: [-0.016, 0.045]Mix model

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo at 12 hourp-value: <0.00190% CI: [0.087, 0.161]Mix model

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo at 24 hourp-value: <0.00190% CI: [0.105, 0.176]Mix model

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo at 1 hourp-value: 0.15590% CI: [-0.012, 0.05]Mix model

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo at 12 hourp-value: <0.00190% CI: [0.053, 0.129]Mix model

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo at 24 hourp-value: <0.00190% CI: [0.09, 0.162]Mix model

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo at 1 hourp-value: 0.18890% CI: [-0.015, 0.048]Mix model

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo at 12 hourp-value: =0.00990% CI: [0.017, 0.093]Mix model

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo at 24 hourp-value: <0.00190% CI: [0.086, 0.159]Mix model

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).

Time frame: Up to 82 days

Population: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration	NA h*pg/mL	—
GSK961081 1200 mg Plus SAL	Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration	233.93 h*pg/mL	Geometric Coefficient of Variation 139
GSK961081 400 mg Plus IPR	Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration	NA h*pg/mL	—
GSK961081 1200 mg Plus IPR	Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration	216.22 h*pg/mL	Geometric Coefficient of Variation 131.3
GSK961081 400 mg Plus Placebo	Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration	NA h*pg/mL	—
GSK961081 1200 mg Plus Placebo	Area Under Plasma Concentration Time Curve (AUC) of GSK961081 to the Last Quantifiable Concentration	229.51 h*pg/mL	Geometric Coefficient of Variation 128.6

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.

Time frame: Up to 27 hours post Day 1 dosing

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 1h	-1.59 Millimeters of mercury (mm of Hg)	Standard Deviation 6.754
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 4h	-2.36 Millimeters of mercury (mm of Hg)	Standard Deviation 8.963
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 13h	-5.62 Millimeters of mercury (mm of Hg)	Standard Deviation 11.947
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 2h	-4.15 Millimeters of mercury (mm of Hg)	Standard Deviation 7.744
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 25h	-2.26 Millimeters of mercury (mm of Hg)	Standard Deviation 6.976
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 9h	-1.59 Millimeters of mercury (mm of Hg)	Standard Deviation 7.923
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 9h	-0.87 Millimeters of mercury (mm of Hg)	Standard Deviation 12.064
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 1 hour(h)	-1.33 Millimeters of mercury (mm of Hg)	Standard Deviation 12.321
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 24h	-0.95 Millimeters of mercury (mm of Hg)	Standard Deviation 6.411
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 4h	-0.26 Millimeters of mercury (mm of Hg)	Standard Deviation 6.332
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 27h	-5.59 Millimeters of mercury (mm of Hg)	Standard Deviation 9.999
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 12h	-3.49 Millimeters of mercury (mm of Hg)	Standard Deviation 11.85
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 27h	-3.28 Millimeters of mercury (mm of Hg)	Standard Deviation 7.229
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 2h	-3.41 Millimeters of mercury (mm of Hg)	Standard Deviation 10.918
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 12h	-3.18 Millimeters of mercury (mm of Hg)	Standard Deviation 8.742
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 24h	-3.31 Millimeters of mercury (mm of Hg)	Standard Deviation 12.092
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 25h	-3.38 Millimeters of mercury (mm of Hg)	Standard Deviation 11.679
GSK961081 400 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 13h	-4.19 Millimeters of mercury (mm of Hg)	Standard Deviation 11.638
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 25h	4.05 Millimeters of mercury (mm of Hg)	Standard Deviation 14.022
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 1h	-1.41 Millimeters of mercury (mm of Hg)	Standard Deviation 6.34
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 4h	1.23 Millimeters of mercury (mm of Hg)	Standard Deviation 6.078
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 2h	-2.27 Millimeters of mercury (mm of Hg)	Standard Deviation 7.871
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 27h	-0.03 Millimeters of mercury (mm of Hg)	Standard Deviation 8.192
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 2h	1.22 Millimeters of mercury (mm of Hg)	Standard Deviation 10.741
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 24h	4.65 Millimeters of mercury (mm of Hg)	Standard Deviation 10.843
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 25h	0.75 Millimeters of mercury (mm of Hg)	Standard Deviation 7.171
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 27h	2.43 Millimeters of mercury (mm of Hg)	Standard Deviation 11.67
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 4h	4.20 Millimeters of mercury (mm of Hg)	Standard Deviation 12.107
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 9h	3.08 Millimeters of mercury (mm of Hg)	Standard Deviation 10.598
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 24h	3.13 Millimeters of mercury (mm of Hg)	Standard Deviation 8.624
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 12h	2.08 Millimeters of mercury (mm of Hg)	Standard Deviation 15.895
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 13h	3.46 Millimeters of mercury (mm of Hg)	Standard Deviation 13.742
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 13h	-1.97 Millimeters of mercury (mm of Hg)	Standard Deviation 7.856
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 12h	-1.25 Millimeters of mercury (mm of Hg)	Standard Deviation 7.655
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 9h	0.03 Millimeters of mercury (mm of Hg)	Standard Deviation 7.882
GSK961081 1200 mg Plus SAL	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 1 hour(h)	3.10 Millimeters of mercury (mm of Hg)	Standard Deviation 11.115
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 1 hour(h)	0.61 Millimeters of mercury (mm of Hg)	Standard Deviation 10.703
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 13h	1.05 Millimeters of mercury (mm of Hg)	Standard Deviation 11.866
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 27h	-2.51 Millimeters of mercury (mm of Hg)	Standard Deviation 7.871
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 9h	1.07 Millimeters of mercury (mm of Hg)	Standard Deviation 10.9
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 25h	1.24 Millimeters of mercury (mm of Hg)	Standard Deviation 8.166
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 2h	3.49 Millimeters of mercury (mm of Hg)	Standard Deviation 7.919
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 24h	1.41 Millimeters of mercury (mm of Hg)	Standard Deviation 11.469
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 2h	0.07 Millimeters of mercury (mm of Hg)	Standard Deviation 7.438
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 12h	-2.68 Millimeters of mercury (mm of Hg)	Standard Deviation 8.329
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 9h	-1.73 Millimeters of mercury (mm of Hg)	Standard Deviation 7.82
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 4h	1.24 Millimeters of mercury (mm of Hg)	Standard Deviation 6.689
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 1h	1.25 Millimeters of mercury (mm of Hg)	Standard Deviation 8.002
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 25h	2.32 Millimeters of mercury (mm of Hg)	Standard Deviation 13.083
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 12h	-0.46 Millimeters of mercury (mm of Hg)	Standard Deviation 11.145
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 24h	0.37 Millimeters of mercury (mm of Hg)	Standard Deviation 5.634
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 27h	-3.24 Millimeters of mercury (mm of Hg)	Standard Deviation 11.432
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 13h	-0.56 Millimeters of mercury (mm of Hg)	Standard Deviation 8.152
GSK961081 400 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 4h	3.27 Millimeters of mercury (mm of Hg)	Standard Deviation 9.68
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 24h	2.32 Millimeters of mercury (mm of Hg)	Standard Deviation 7.932
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 1 hour(h)	-1.73 Millimeters of mercury (mm of Hg)	Standard Deviation 10.301
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 2h	2.33 Millimeters of mercury (mm of Hg)	Standard Deviation 11.45
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 4h	2.68 Millimeters of mercury (mm of Hg)	Standard Deviation 9.689
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 9h	2.71 Millimeters of mercury (mm of Hg)	Standard Deviation 12.125
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 12h	0.32 Millimeters of mercury (mm of Hg)	Standard Deviation 12.445
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 13h	2.27 Millimeters of mercury (mm of Hg)	Standard Deviation 13.808
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 24h	2.56 Millimeters of mercury (mm of Hg)	Standard Deviation 12.616
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 25h	2.44 Millimeters of mercury (mm of Hg)	Standard Deviation 9.453
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 27h	-0.32 Millimeters of mercury (mm of Hg)	Standard Deviation 12.875
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 1h	-2.66 Millimeters of mercury (mm of Hg)	Standard Deviation 6.814
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 2h	0.48 Millimeters of mercury (mm of Hg)	Standard Deviation 6.939
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 4h	0.12 Millimeters of mercury (mm of Hg)	Standard Deviation 8.134
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 9h	-0.34 Millimeters of mercury (mm of Hg)	Standard Deviation 9.175
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 12h	-0.90 Millimeters of mercury (mm of Hg)	Standard Deviation 7.605
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 13h	-0.39 Millimeters of mercury (mm of Hg)	Standard Deviation 7.602
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 25h	1.49 Millimeters of mercury (mm of Hg)	Standard Deviation 8.474
GSK961081 1200 mg Plus IPR	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 27h	-1.12 Millimeters of mercury (mm of Hg)	Standard Deviation 7.541
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 9h	0.28 Millimeters of mercury (mm of Hg)	Standard Deviation 6.373
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 12h	-1.95 Millimeters of mercury (mm of Hg)	Standard Deviation 11.618
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 12h	-3.05 Millimeters of mercury (mm of Hg)	Standard Deviation 7.414
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 9h	0.00 Millimeters of mercury (mm of Hg)	Standard Deviation 9.748
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 27h	-3.25 Millimeters of mercury (mm of Hg)	Standard Deviation 10.463
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 24h	-0.23 Millimeters of mercury (mm of Hg)	Standard Deviation 6.799
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 4h	0.63 Millimeters of mercury (mm of Hg)	Standard Deviation 10.947
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 25h	-0.10 Millimeters of mercury (mm of Hg)	Standard Deviation 12.349
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 2h	1.03 Millimeters of mercury (mm of Hg)	Standard Deviation 8.195
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 27h	-3.35 Millimeters of mercury (mm of Hg)	Standard Deviation 9.27
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 25h	0.78 Millimeters of mercury (mm of Hg)	Standard Deviation 5.753
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 13h	3.45 Millimeters of mercury (mm of Hg)	Standard Deviation 15.591
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 2h	-1.48 Millimeters of mercury (mm of Hg)	Standard Deviation 6.473
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 1 hour(h)	-0.13 Millimeters of mercury (mm of Hg)	Standard Deviation 12.096
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 24h	-1.50 Millimeters of mercury (mm of Hg)	Standard Deviation 10.627
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 1h	0.55 Millimeters of mercury (mm of Hg)	Standard Deviation 6.737
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 13h	0.85 Millimeters of mercury (mm of Hg)	Standard Deviation 9.67
GSK961081 400 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 4h	1.38 Millimeters of mercury (mm of Hg)	Standard Deviation 8.35
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 13h	-0.34 Millimeters of mercury (mm of Hg)	Standard Deviation 8.38
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 27h	-1.24 Millimeters of mercury (mm of Hg)	Standard Deviation 10.899
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 25h	1.49 Millimeters of mercury (mm of Hg)	Standard Deviation 11.428
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 9h	-0.79 Millimeters of mercury (mm of Hg)	Standard Deviation 8.581
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 24h	1.68 Millimeters of mercury (mm of Hg)	Standard Deviation 10.547
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 24h	-0.58 Millimeters of mercury (mm of Hg)	Standard Deviation 7.31
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 12h	-0.51 Millimeters of mercury (mm of Hg)	Standard Deviation 7.026
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 13h	2.21 Millimeters of mercury (mm of Hg)	Standard Deviation 9.935
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 12h	-0.51 Millimeters of mercury (mm of Hg)	Standard Deviation 10.45
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 27h	-1.55 Millimeters of mercury (mm of Hg)	Standard Deviation 7.202
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 4h	1.54 Millimeters of mercury (mm of Hg)	Standard Deviation 6.353
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 9h	2.95 Millimeters of mercury (mm of Hg)	Standard Deviation 12.237
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 4h	2.38 Millimeters of mercury (mm of Hg)	Standard Deviation 10.101
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 2h	1.31 Millimeters of mercury (mm of Hg)	Standard Deviation 12.131
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 25h	2.22 Millimeters of mercury (mm of Hg)	Standard Deviation 7.536
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 2h	-1.05 Millimeters of mercury (mm of Hg)	Standard Deviation 7.189
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	DBP, 1h	-2.21 Millimeters of mercury (mm of Hg)	Standard Deviation 8.594
GSK961081 1200 mg Plus Placebo	Change From Baseline (Pre-dose on Day 1) in Systolic and Diastolic Blood Pressure up to 27 Hours	SBP, 1 hour(h)	-0.33 Millimeters of mercury (mm of Hg)	Standard Deviation 11.235

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.

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

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	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.	1 hour	0.169 Liters	Standard Error 0.046
GSK961081 400 mg Plus SAL	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.	24 hour	0.247 Liters	Standard Error 0.0398
GSK961081 400 mg Plus SAL	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.	12 hour	0.160 Liters	Standard Error 0.038
GSK961081 1200 mg Plus SAL	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.	24 hour	0.205 Liters	Standard Error 0.0392
GSK961081 1200 mg Plus SAL	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.	12 hour	0.182 Liters	Standard Error 0.0375
GSK961081 1200 mg Plus SAL	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.	1 hour	0.281 Liters	Standard Error 0.0449
GSK961081 400 mg Plus IPR	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.	1 hour	0.167 Liters	Standard Error 0.0454
GSK961081 400 mg Plus IPR	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.	24 hour	0.279 Liters	Standard Error 0.0388
GSK961081 400 mg Plus IPR	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.	12 hour	0.188 Liters	Standard Error 0.0375
GSK961081 1200 mg Plus IPR	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.	12 hour	0.223 Liters	Standard Error 0.0375
GSK961081 1200 mg Plus IPR	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.	1 hour	0.207 Liters	Standard Error 0.0454
GSK961081 1200 mg Plus IPR	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.	24 hour	0.214 Liters	Standard Error 0.0397
GSK961081 400 mg Plus Placebo	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.	12 hour	0.068 Liters	Standard Error 0.0375
GSK961081 400 mg Plus Placebo	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.	1 hour	0.234 Liters	Standard Error 0.0454
GSK961081 400 mg Plus Placebo	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.	24 hour	0.179 Liters	Standard Error 0.0393
GSK961081 1200 mg Plus Placebo	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.	1 hour	0.229 Liters	Standard Error 0.0472
GSK961081 1200 mg Plus Placebo	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.	24 hour	0.113 Liters	Standard Error 0.0407
GSK961081 1200 mg Plus Placebo	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.	12 hour	0.088 Liters	Standard Error 0.0385

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo at 12 hourp-value: =0.00890% CI: [0.039, 0.201]Mix model

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo at 1 hourp-value: =0.85690% CI: [-0.168, 0.036]Mix model

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo at 12 hourp-value: =0.03390% CI: [0.01, 0.174]Mix model

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo at 24 hourp-value: =0.09990% CI: [-0.019, 0.154]Mix model

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo at 1 hourp-value: =0.86290% CI: [-0.168, 0.034]Mix model

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo at 24 hourp-value: 0.02790% CI: [0.015, 0.185]Mix model

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo at 1 hourp-value: =0.290% CI: [-0.05, 0.155]Mix model

Comparison: GSK961081 1200 mcg Plus SAL versus that due to GSK961081 1200 mcg plus Placebo at 12 hourp-value: =0.03190% CI: [0.011, 0.177]Mix model

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo at 24 hourp-value: =0.04390% CI: [0.004, 0.179]Mix model

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo at 1 hourp-value: =0.63790% CI: [-0.125, 0.081]Mix model

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo at 12 hourp-value: =0.00490% CI: [0.053, 0.218]Mix model

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo at 24 hourp-value: =0.03190% CI: [0.012, 0.189]Mix model

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.

Time frame: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	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	MC from BL, Glu, 0-27h	2.71 Millimoles per Liter	Standard Error 0.236
GSK961081 400 mg Plus SAL	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	MC from BL, Glu, 0-4h	0.66 Millimoles per Liter	Standard Error 0.186
GSK961081 400 mg Plus SAL	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	WMC from BL, Glu, 0-4h	0.02 Millimoles per Liter	Standard Error 0.083
GSK961081 1200 mg Plus SAL	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	MC from BL, Glu, 0-27h	2.13 Millimoles per Liter	Standard Error 0.23
GSK961081 1200 mg Plus SAL	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	MC from BL, Glu, 0-4h	0.53 Millimoles per Liter	Standard Error 0.182
GSK961081 1200 mg Plus SAL	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	WMC from BL, Glu, 0-4h	0.02 Millimoles per Liter	Standard Error 0.081
GSK961081 400 mg Plus IPR	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	MC from BL, Glu, 0-27h	1.78 Millimoles per Liter	Standard Error 0.23
GSK961081 400 mg Plus IPR	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	MC from BL, Glu, 0-4h	0.52 Millimoles per Liter	Standard Error 0.182
GSK961081 400 mg Plus IPR	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	WMC from BL, Glu, 0-4h	-0.12 Millimoles per Liter	Standard Error 0.081
GSK961081 1200 mg Plus IPR	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	MC from BL, Glu, 0-27h	1.87 Millimoles per Liter	Standard Error 0.235
GSK961081 1200 mg Plus IPR	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	MC from BL, Glu, 0-4h	0.53 Millimoles per Liter	Standard Error 0.186
GSK961081 1200 mg Plus IPR	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	WMC from BL, Glu, 0-4h	-0.08 Millimoles per Liter	Standard Error 0.082
GSK961081 400 mg Plus Placebo	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	MC from BL, Glu, 0-27h	1.83 Millimoles per Liter	Standard Error 0.232
GSK961081 400 mg Plus Placebo	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	MC from BL, Glu, 0-4h	0.13 Millimoles per Liter	Standard Error 0.184
GSK961081 400 mg Plus Placebo	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	WMC from BL, Glu, 0-4h	-0.29 Millimoles per Liter	Standard Error 0.082
GSK961081 1200 mg Plus Placebo	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	MC from BL, Glu, 0-4h	0.22 Millimoles per Liter	Standard Error 0.189
GSK961081 1200 mg Plus Placebo	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	WMC from BL, Glu, 0-4h	0.19 Millimoles per Liter	Standard Error 0.085
GSK961081 1200 mg Plus Placebo	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	MC from BL, Glu, 0-27h	1.30 Millimoles per Liter	Standard Error 0.239

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [0.066, 0.994]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-0.069, 0.846]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-0.157, 0.775]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-0.163, 0.78]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [0.262, 1.485]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-0.656, 0.55]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [0.215, 1.443]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-0.054, 1.189]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours (WMC)95% CI: [0.11, 0.513]

Comparison: GSK961081 400 mcg Plus IPR versus maximum GSK961081 400 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-0.025, 0.372]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours (WMC)95% CI: [0.006, 0.414]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-0.103, 0.311]

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 .

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

Population: Modified Per Protocol population.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	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	0-27 hours	24.17 msec	Standard Error 2.39
GSK961081 400 mg Plus SAL	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	0-4 hours	16.70 msec	Standard Error 2.078
GSK961081 1200 mg Plus SAL	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	0-4 hours	19.51 msec	Standard Error 2.035
GSK961081 1200 mg Plus SAL	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	0-27 hours	25.88 msec	Standard Error 2.339
GSK961081 400 mg Plus IPR	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	0-27 hours	17.33 msec	Standard Error 2.337
GSK961081 400 mg Plus IPR	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	0-4 hours	9.19 msec	Standard Error 2.033
GSK961081 1200 mg Plus IPR	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	0-27 hours	17.83 msec	Standard Error 2.353
GSK961081 1200 mg Plus IPR	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	0-4 hours	10.77 msec	Standard Error 2.047
GSK961081 400 mg Plus Placebo	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	0-4 hours	6.50 msec	Standard Error 2.054
GSK961081 400 mg Plus Placebo	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	0-27 hours	12.94 msec	Standard Error 2.362
GSK961081 1200 mg Plus Placebo	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	0-4 hours	11.65 msec	Standard Error 2.109
GSK961081 1200 mg Plus Placebo	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	0-27 hours	19.91 msec	Standard Error 2.429

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [5.258, 15.139]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-2.195, 7.567]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [2.883, 12.825]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-5.864, 4.097]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [5.352, 17.103]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-1.418, 10.197]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [0.065, 11.886]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-8.006, 3.84]

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 .

Time frame: From dosing until 27 hours (0-27h)

Population: Modified per protocol population

Arm	Measure	Value (MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing	19.70 msec	Standard Deviation 2.152
GSK961081 1200 mg Plus SAL	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing	19.53 msec	Standard Deviation 2.104
GSK961081 400 mg Plus IPR	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing	17.41 msec	Standard Deviation 2.1
GSK961081 1200 mg Plus IPR	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing	17.45 msec	Standard Deviation 2.119
GSK961081 400 mg Plus Placebo	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing	15.14 msec	Standard Deviation 2.125
GSK961081 1200 mg Plus Placebo	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 27 Hours After Dosing	18.60 msec	Standard Deviation 2.184

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo over 0-27 hours95% CI: [-0.781, 9.897]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo over 0-27 hours95% CI: [-2.999, 7.532]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo over 0-27 hours95% CI: [-4.429, 6.29]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo over 0-27 hours95% CI: [-6.539, 4.236]

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.

Time frame: From dosing until 4 hours (0-4h)

Population: Modified per protocol population

Arm	Measure	Value (MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing	14.34 msec	Standard Deviation 1.865
GSK961081 1200 mg Plus SAL	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing	14.98 msec	Standard Deviation 1.827
GSK961081 400 mg Plus IPR	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing	12.31 msec	Standard Deviation 1.824
GSK961081 1200 mg Plus IPR	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing	11.99 msec	Standard Deviation 1.839
GSK961081 400 mg Plus Placebo	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing	10.60 msec	Standard Deviation 1.844
GSK961081 1200 mg Plus Placebo	Maximum Change From Baseline (Pre-dose on Day 1) in QTc (F) in Supine Position From 0 to 4 Hours After Dosing	13.22 msec	Standard Deviation 1.89

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo over 0-4 hours95% CI: [-0.547, 8.041]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo over 0-4 hours95% CI: [-2.521, 5.944]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo over 0-4 hours95% CI: [-2.559, 6.069]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo over 0-4 hours95% CI: [-5.565, 3.103]

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.

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

Population: Modified Per Protocol population.

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-27 h	13.33 Beats per minute	Standard Error 1.011
GSK961081 400 mg Plus SAL	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-4 h	7.51 Beats per minute	Standard Error 1.125
GSK961081 1200 mg Plus SAL	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-4 h	7.90 Beats per minute	Standard Error 1.099
GSK961081 1200 mg Plus SAL	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-27 h	12.92 Beats per minute	Standard Error 0.988
GSK961081 400 mg Plus IPR	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-4 h	2.18 Beats per minute	Standard Error 1.097
GSK961081 400 mg Plus IPR	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-27 h	9.49 Beats per minute	Standard Error 0.987
GSK961081 1200 mg Plus IPR	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-4 h	3.17 Beats per minute	Standard Error 1.109
GSK961081 1200 mg Plus IPR	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-27 h	10.28 Beats per minute	Standard Error 0.998
GSK961081 400 mg Plus Placebo	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-4 h	0.92 Beats per minute	Standard Error 1.11
GSK961081 400 mg Plus Placebo	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-27 h	9.21 Beats per minute	Standard Error 0.998
GSK961081 1200 mg Plus Placebo	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-27 h	8.66 Beats per minute	Standard Error 1.024
GSK961081 1200 mg Plus Placebo	Maximum Change From Baseline (Pre-dose on Day 1) in Supine Heart Rate From 0 to 4 Hours and From 0 to 27 Hours.	0-4 h	0.92 Beats per minute	Standard Error 1.139

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [3.839, 9.336]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-1.453, 3.962]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [4.231, 9.738]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-0.522, 5.031]

Comparison: GSK961081 400 mcg Plus SAL versus maximal GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [1.662, 6.58]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-2.142, 2.703]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [1.802, 6.729]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-0.863, 4.106]

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.

Time frame: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	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	MC from BL,SBP,0-27h	10.89 Millimeters of mercury	Standard Error 1.53
GSK961081 400 mg Plus SAL	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	WMC from BL SBP,0-4h	-0.34 Millimeters of mercury	Standard Error 1.103
GSK961081 400 mg Plus SAL	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	MC from BL,SBP,0-4h	5.61 Millimeters of mercury	Standard Error 1.452
GSK961081 1200 mg Plus SAL	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	WMC from BL SBP,0-4h	0.92 Millimeters of mercury	Standard Error 1.071
GSK961081 1200 mg Plus SAL	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	MC from BL,SBP,0-27h	15.93 Millimeters of mercury	Standard Error 1.488
GSK961081 1200 mg Plus SAL	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	MC from BL,SBP,0-4h	8.06 Millimeters of mercury	Standard Error 1.409
GSK961081 400 mg Plus IPR	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	MC from BL,SBP,0-4h	8.05 Millimeters of mercury	Standard Error 1.394
GSK961081 400 mg Plus IPR	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	MC from BL,SBP,0-27h	14.08 Millimeters of mercury	Standard Error 1.477
GSK961081 400 mg Plus IPR	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	WMC from BL SBP,0-4h	2.24 Millimeters of mercury	Standard Error 1.063
GSK961081 1200 mg Plus IPR	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	MC from BL,SBP,0-27h	12.87 Millimeters of mercury	Standard Error 1.495
GSK961081 1200 mg Plus IPR	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	MC from BL,SBP,0-4h	5.55 Millimeters of mercury	Standard Error 1.414
GSK961081 1200 mg Plus IPR	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	WMC from BL SBP,0-4h	0.10 Millimeters of mercury	Standard Error 1.076
GSK961081 400 mg Plus Placebo	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	MC from BL,SBP,0-27h	14.16 Millimeters of mercury	Standard Error 1.493
GSK961081 400 mg Plus Placebo	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	MC from BL,SBP,0-4h	7.45 Millimeters of mercury	Standard Error 1.412
GSK961081 400 mg Plus Placebo	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	WMC from BL SBP,0-4h	1.06 Millimeters of mercury	Standard Error 1.075
GSK961081 1200 mg Plus Placebo	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	MC from BL,SBP,0-4h	7.74 Millimeters of mercury	Standard Error 1.448
GSK961081 1200 mg Plus Placebo	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	WMC from BL SBP,0-4h	0.82 Millimeters of mercury	Standard Error 1.113
GSK961081 1200 mg Plus Placebo	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	MC from BL,SBP,0-27h	14.10 Millimeters of mercury	Standard Error 1.527

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-5.42, 1.748]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-2.914, 4.113]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-3.261, 3.909]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-5.781, 1.416]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-6.762, 0.23]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-3.502, 3.348]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-1.673, 5.327]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-4.743, 2.279]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-3.976, 1.187]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-1.348, 3.71]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-2.498, 2.71]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-3.325, 1.899]

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).

Time frame: Up to 82 days

Population: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	66.93 pg/mL	Geometric Coefficient of Variation 55
GSK961081 1200 mg Plus SAL	Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	169.05 pg/mL	Geometric Coefficient of Variation 66.2
GSK961081 400 mg Plus IPR	Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	70.77 pg/mL	Geometric Coefficient of Variation 54.8
GSK961081 1200 mg Plus IPR	Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	153.59 pg/mL	Geometric Coefficient of Variation 50.5
GSK961081 400 mg Plus Placebo	Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	70.52 pg/mL	Geometric Coefficient of Variation 60.9
GSK961081 1200 mg Plus Placebo	Maximum Plasma Concentration (Cmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	176.92 pg/mL	Geometric Coefficient of Variation 47.9

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.

Time frame: Up to 27 hours post Day 1 dosing

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

Arm	Measure	Group	Value (MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h	1.95 Beats per minute	Standard Deviation 7.567
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	9h	1.92 Beats per minute	Standard Deviation 6.247
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 35 minutes	-0.03 Beats per minute	Standard Deviation 8.481
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 35 minutes	0.23 Beats per minute	Standard Deviation 8.806
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	4h	-0.71 Beats per minute	Standard Deviation 11.094
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 55 minutes	3.21 Beats per minute	Standard Deviation 9.359
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h	-2.56 Beats per minute	Standard Deviation 10.246
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	27h	6.74 Beats per minute	Standard Deviation 9.402
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 15 minutes	-1.49 Beats per minute	Standard Deviation 8.705
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h	-2.36 Beats per minute	Standard Deviation 8.142
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 55 minutes	5.79 Beats per minute	Standard Deviation 8.694
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 15 minutes	-0.95 Beats per minute	Standard Deviation 8.712
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 55 minutes	1.05 Beats per minute	Standard Deviation 8.617
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 35 minutes	4.97 Beats per minute	Standard Deviation 7.741
GSK961081 400 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 15 minutes	3.95 Beats per minute	Standard Deviation 7.729
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 15 minutes	-1.60 Beats per minute	Standard Deviation 7.938
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	9h	2.97 Beats per minute	Standard Deviation 6.815
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h	-1.08 Beats per minute	Standard Deviation 7.145
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h	-1.37 Beats per minute	Standard Deviation 8.546
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 15 minutes	-0.46 Beats per minute	Standard Deviation 7.328
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 35 minutes	1.51 Beats per minute	Standard Deviation 7.166
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 55 minutes	4.54 Beats per minute	Standard Deviation 7.246
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	4h	1.13 Beats per minute	Standard Deviation 6.501
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h	3.65 Beats per minute	Standard Deviation 8.469
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 15 minutes	5.35 Beats per minute	Standard Deviation 7.608
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 35 minutes	6.90 Beats per minute	Standard Deviation 7.558
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 55 minutes	6.50 Beats per minute	Standard Deviation 8.124
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 35 minutes	0.53 Beats per minute	Standard Deviation 7.99
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 55 minutes	0.83 Beats per minute	Standard Deviation 8.65
GSK961081 1200 mg Plus SAL	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	27h	6.38 Beats per minute	Standard Deviation 9.44
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 55 minutes	-3.46 Beats per minute	Standard Deviation 7.232
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 15 minutes	1.83 Beats per minute	Standard Deviation 6.364
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	9h	-1.66 Beats per minute	Standard Deviation 7.529
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 35 minutes	1.51 Beats per minute	Standard Deviation 6.856
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 15 minutes	-2.80 Beats per minute	Standard Deviation 7.118
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	4h	-3.59 Beats per minute	Standard Deviation 9.389
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 35 minutes	-2.93 Beats per minute	Standard Deviation 6.218
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 15 minutes	-0.83 Beats per minute	Standard Deviation 7.297
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h	-3.90 Beats per minute	Standard Deviation 7.761
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h	-3.24 Beats per minute	Standard Deviation 5.267
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h	1.46 Beats per minute	Standard Deviation 8.521
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 35 minutes	-2.34 Beats per minute	Standard Deviation 7.275
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 55 minutes	1.07 Beats per minute	Standard Deviation 7.424
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	27h	1.17 Beats per minute	Standard Deviation 9.132
GSK961081 400 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 55 minutes	-2.46 Beats per minute	Standard Deviation 9.223
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 35 minutes	-1.02 Beats per minute	Standard Deviation 6.901
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	9h	1.37 Beats per minute	Standard Deviation 7.569
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h	2.83 Beats per minute	Standard Deviation 7.752
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 15 minutes	-0.15 Beats per minute	Standard Deviation 6.624
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 15 minutes	4.10 Beats per minute	Standard Deviation 7.612
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 35 minutes	3.41 Beats per minute	Standard Deviation 8.465
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 55 minutes	1.90 Beats per minute	Standard Deviation 7.671
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h	-1.85 Beats per minute	Standard Deviation 7.189
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h	-2.27 Beats per minute	Standard Deviation 7.099
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 15 minutes	-0.98 Beats per minute	Standard Deviation 7.666
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	27h	4.44 Beats per minute	Standard Deviation 9.394
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	4h	-1.78 Beats per minute	Standard Deviation 6.031
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 55 minutes	-0.39 Beats per minute	Standard Deviation 6.629
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 35 minutes	-0.98 Beats per minute	Standard Deviation 5.943
GSK961081 1200 mg Plus IPR	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 55 minutes	-2.05 Beats per minute	Standard Deviation 6.488
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 55 minutes	0.98 Beats per minute	Standard Deviation 7.416
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h	-3.55 Beats per minute	Standard Deviation 9.047
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h	-3.63 Beats per minute	Standard Deviation 8.079
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 55 minutes	-4.13 Beats per minute	Standard Deviation 7.198
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 15 minutes	-4.03 Beats per minute	Standard Deviation 7.54
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	4h	-4.75 Beats per minute	Standard Deviation 6.636
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 15 minutes	-2.95 Beats per minute	Standard Deviation 6.972
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 55 minutes	-3.63 Beats per minute	Standard Deviation 6.636
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	9h	-0.70 Beats per minute	Standard Deviation 8.879
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 35 minutes	-4.48 Beats per minute	Standard Deviation 6.361
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	27h	2.05 Beats per minute	Standard Deviation 7.968
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 15 minutes	1.80 Beats per minute	Standard Deviation 6.992
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 35 minutes	2.28 Beats per minute	Standard Deviation 6.52
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h	2.68 Beats per minute	Standard Deviation 8.689
GSK961081 400 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 35 minutes	-3.63 Beats per minute	Standard Deviation 6.717
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 55 minutes	-2.21 Beats per minute	Standard Deviation 6.42
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 55 minutes	1.37 Beats per minute	Standard Deviation 8.065
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h	1.87 Beats per minute	Standard Deviation 6.993
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 55 minutes	-4.21 Beats per minute	Standard Deviation 7.037
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 35 minutes	-2.36 Beats per minute	Standard Deviation 6.098
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 35 minutes	-4.63 Beats per minute	Standard Deviation 6.724
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	4h	-3.97 Beats per minute	Standard Deviation 7.069
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 35 minutes	1.29 Beats per minute	Standard Deviation 6.534
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	9h	0.28 Beats per minute	Standard Deviation 7.215
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	12h 15 minutes	2.05 Beats per minute	Standard Deviation 8.22
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	27h	2.68 Beats per minute	Standard Deviation 8.817
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h 15 minutes	-4.03 Beats per minute	Standard Deviation 8.284
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	24h	-4.55 Beats per minute	Standard Deviation 7.576
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h	-3.10 Beats per minute	Standard Deviation 6.585
GSK961081 1200 mg Plus Placebo	Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate Over 27 Hours	1h 15 minutes	-1.74 Beats per minute	Standard Deviation 5.915

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.

Time frame: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	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	MC from BL, K, 0-27h	-0.53 Millimoles per Liter	Standard Error 0.042
GSK961081 400 mg Plus SAL	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	WMC from BL, K, 0-4h	-0.18 Millimoles per Liter	Standard Error 0.042
GSK961081 400 mg Plus SAL	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	MC from BL, K, 0-4h	-0.42 Millimoles per Liter	Standard Error 0.042
GSK961081 1200 mg Plus SAL	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	WMC from BL, K, 0-4h	-0.22 Millimoles per Liter	Standard Error 0.04
GSK961081 1200 mg Plus SAL	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	MC from BL, K, 0-27h	-0.62 Millimoles per Liter	Standard Error 0.04
GSK961081 1200 mg Plus SAL	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	MC from BL, K, 0-4h	-0.44 Millimoles per Liter	Standard Error 0.041
GSK961081 400 mg Plus IPR	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	MC from BL, K, 0-4h	-0.25 Millimoles per Liter	Standard Error 0.041
GSK961081 400 mg Plus IPR	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	MC from BL, K, 0-27h	-0.42 Millimoles per Liter	Standard Error 0.041
GSK961081 400 mg Plus IPR	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	WMC from BL, K, 0-4h	-0.06 Millimoles per Liter	Standard Error 0.04
GSK961081 1200 mg Plus IPR	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	MC from BL, K, 0-27h	-0.46 Millimoles per Liter	Standard Error 0.041
GSK961081 1200 mg Plus IPR	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	MC from BL, K, 0-4h	-0.39 Millimoles per Liter	Standard Error 0.042
GSK961081 1200 mg Plus IPR	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	WMC from BL, K, 0-4h	-0.17 Millimoles per Liter	Standard Error 0.041
GSK961081 400 mg Plus Placebo	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	MC from BL, K, 0-27h	-0.37 Millimoles per Liter	Standard Error 0.041
GSK961081 400 mg Plus Placebo	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	MC from BL, K, 0-4h	-0.25 Millimoles per Liter	Standard Error 0.041
GSK961081 400 mg Plus Placebo	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	WMC from BL, K, 0-4h	-0.07 Millimoles per Liter	Standard Error 0.041
GSK961081 1200 mg Plus Placebo	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	MC from BL, K, 0-4h	-0.36 Millimoles per Liter	Standard Error 0.042
GSK961081 1200 mg Plus Placebo	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	WMC from BL, K, 0-4h	-0.14 Millimoles per Liter	Standard Error 0.042
GSK961081 1200 mg Plus Placebo	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	MC from BL, K, 0-27h	-0.45 Millimoles per Liter	Standard Error 0.042

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-0.276, -0.078]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-0.096, 0.097]

Comparison: SK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-0.174, 0.022]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-0.128, 0.072]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-0.263, -0.069]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-0.152, 0.038]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-0.267, -0.075]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-0.108, 0.089]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-0.211, -0.005]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-0.087, 0.114]

Comparison: GSK961081 1200 mcg Plus SAL GSK961081 1200 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-0.18, 0.026]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-0.129, 0.08]

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 .

Time frame: 0-4h and 0-27h for maximum change and 0-4 h for weighted mean change

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

Arm	Measure	Group	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	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	MC from BL, DBP, 0-27h	-10.04 Millimeters of mercury	Standard Error 0.953
GSK961081 400 mg Plus SAL	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	MC from BL, DBP, 0-4h	-5.53 Millimeters of mercury	Standard Error 0.971
GSK961081 400 mg Plus SAL	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	WMC from BL, DBP, 0-4h	-1.30 Millimeters of mercury	Standard Error 0.733
GSK961081 1200 mg Plus SAL	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	MC from BL, DBP, 0-27h	-9.20 Millimeters of mercury	Standard Error 0.93
GSK961081 1200 mg Plus SAL	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	MC from BL, DBP, 0-4h	-5.76 Millimeters of mercury	Standard Error 0.946
GSK961081 1200 mg Plus SAL	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	WMC from BL, DBP, 0-4h	-1.25 Millimeters of mercury	Standard Error 0.715
GSK961081 400 mg Plus IPR	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	MC from BL, DBP, 0-27h	-9.12 Millimeters of mercury	Standard Error 0.928
GSK961081 400 mg Plus IPR	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	MC from BL, DBP, 0-4h	-3.26 Millimeters of mercury	Standard Error 0.942
GSK961081 400 mg Plus IPR	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	WMC from BL, DBP, 0-4h	0.75 Millimeters of mercury	Standard Error 0.713
GSK961081 1200 mg Plus IPR	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	MC from BL, DBP, 0-27h	-8.72 Millimeters of mercury	Standard Error 0.938
GSK961081 1200 mg Plus IPR	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	MC from BL, DBP, 0-4h	-5.49 Millimeters of mercury	Standard Error 0.954
GSK961081 1200 mg Plus IPR	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	WMC from BL, DBP, 0-4h	-0.80 Millimeters of mercury	Standard Error 0.721
GSK961081 400 mg Plus Placebo	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	MC from BL, DBP, 0-27h	-9.66 Millimeters of mercury	Standard Error 0.938
GSK961081 400 mg Plus Placebo	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	MC from BL, DBP, 0-4h	-4.96 Millimeters of mercury	Standard Error 0.954
GSK961081 400 mg Plus Placebo	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	WMC from BL, DBP, 0-4h	-0.12 Millimeters of mercury	Standard Error 0.721
GSK961081 1200 mg Plus Placebo	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	MC from BL, DBP, 0-4h	-4.42 Millimeters of mercury	Standard Error 0.979
GSK961081 1200 mg Plus Placebo	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	WMC from BL, DBP, 0-4h	-0.44 Millimeters of mercury	Standard Error 0.747
GSK961081 1200 mg Plus Placebo	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	MC from BL, DBP, 0-27h	-9.18 Millimeters of mercury	Standard Error 0.959

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-2.997, 1.876]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-0.687, 4.097]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-3.771, 1.098]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-3.516, 1.382]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-2.545, 1.794]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-27 hours95% CI: [-1.588, 2.668]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-2.185, 2.154]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-27 hours95% CI: [-1.715, 2.648]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-2.918, 0.559]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-0.829, 2.582]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-2.561, 0.944]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours (WMC)95% CI: [-2.122, 1.401]

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.

Time frame: Upto 82 days

Population: All subjects population

Arm	Measure	Group	Value (NUMBER)
GSK961081 400 mg Plus SAL	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any SAE	0 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any AE	13 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any SAE	1 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any AE	13 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any AE	15 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any SAE	1 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any AE	9 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any SAE	0 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any AE	6 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any SAE	0 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any AE	11 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Adverse Events and Serious Adverse Events	Participants with any SAE	0 Participants

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).

Time frame: Up to 42 days

Population: All subjects population

Arm	Measure	Group	Value (NUMBER)
GSK961081 400 mg Plus SAL	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets low	1 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Hemoglobin high	0 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets high	0 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Lymphocytes low	0 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Lymphocytes low	0 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets low	0 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets high	1 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Hemoglobin high	1 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets high	0 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets low	0 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Hemoglobin high	0 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Lymphocytes low	0 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Hemoglobin high	0 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets high	0 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets low	0 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Lymphocytes low	1 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Lymphocytes low	0 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets high	0 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Hemoglobin high	0 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets low	0 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets high	0 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Platelets low	0 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Lymphocytes low	0 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Laboratory Abnormalities of Potential Clinical Concern (PCC)	Hemoglobin high	0 Participants

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.

Time frame: From dosing until 24h post-dose.

Population: All subjects population

Arm	Measure	Group	Value (NUMBER)
GSK961081 400 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, <=30 msec	34 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >30 to <= 59 msec	12 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, <=30 msec	26 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >=60 msec	0 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >=60 msec	1 Participants
GSK961081 400 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >30 to <= 59 msec	5 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >30 to <= 59 msec	9 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, <=30 msec	31 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >=60 msec	1 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, <=30 msec	31 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >30 to <= 59 msec	9 Participants
GSK961081 1200 mg Plus SAL	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >=60 msec	1 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >=60 msec	2 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >30 to <= 59 msec	6 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >=60 msec	0 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >30 to <= 59 msec	2 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, <=30 msec	37 Participants
GSK961081 400 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, <=30 msec	35 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, <=30 msec	33 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >=60 msec	1 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >30 to <= 59 msec	7 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, <=30 msec	36 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >30 to <= 59 msec	4 Participants
GSK961081 1200 mg Plus IPR	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >=60 msec	1 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >30 to <= 59 msec	3 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >=60 msec	0 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, <=30 msec	36 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >30 to <= 59 msec	4 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, <=30 msec	36 Participants
GSK961081 400 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >=60 msec	1 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, <=30 msec	35 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >30 to <= 59 msec	6 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >30 to <= 59 msec	2 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, <=30 msec	31 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcF, >=60 msec	2 Participants
GSK961081 1200 mg Plus Placebo	Number of Participants With Maximum Change From Baseline 12-LED Electrocardiogram (ECG) Findings	QTcB, >=60 msec	2 Participants

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

Time frame: Up to 82 days

Population: 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.

Arm	Measure	Value (MEDIAN)
GSK961081 400 mg Plus SAL	Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data	0.960 hours
GSK961081 1200 mg Plus SAL	Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data	2.000 hours
GSK961081 400 mg Plus IPR	Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data	1.930 hours
GSK961081 1200 mg Plus IPR	Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data	3.920 hours
GSK961081 400 mg Plus Placebo	Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data	1.920 hours
GSK961081 1200 mg Plus Placebo	Time to Last Quantifiable Plasma Concentration (Tlast) of GSK961081 Over Period Determined Directly From the Concentration-time Data	2.050 hours

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.

Time frame: From dosing until 4 hours (0-4h)

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

Arm	Measure	Group	Value (MEDIAN)
GSK961081 400 mg Plus SAL	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	Diastolic BP	2.100 hours
GSK961081 400 mg Plus SAL	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	Heart rate	1.850 hours
GSK961081 400 mg Plus SAL	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	QTcF	2.183 hours
GSK961081 400 mg Plus SAL	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	Potassium	1.967 hours
GSK961081 400 mg Plus SAL	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	Systlic BP	0.917 hours
GSK961081 400 mg Plus SAL	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	Glucose	1.933 hours
GSK961081 400 mg Plus SAL	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	QTcB	2.100 hours
GSK961081 1200 mg Plus SAL	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	QTcB	2.100 hours
GSK961081 1200 mg Plus SAL	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	Systlic BP	2.100 hours
GSK961081 1200 mg Plus SAL	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	QTcF	2.100 hours
GSK961081 1200 mg Plus SAL	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	Heart rate	1.850 hours
GSK961081 1200 mg Plus SAL	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	Potassium	1.933 hours
GSK961081 1200 mg Plus SAL	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	Diastolic BP	1.967 hours
GSK961081 1200 mg Plus SAL	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	Glucose	1.950 hours
GSK961081 400 mg Plus IPR	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	QTcB	2.100 hours
GSK961081 400 mg Plus IPR	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	Heart rate	1.517 hours
GSK961081 400 mg Plus IPR	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	Systlic BP	2.100 hours
GSK961081 400 mg Plus IPR	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	Diastolic BP	2.100 hours
GSK961081 400 mg Plus IPR	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	QTcF	2.167 hours
GSK961081 400 mg Plus IPR	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	Glucose	0.967 hours
GSK961081 400 mg Plus IPR	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	Potassium	1.933 hours
GSK961081 1200 mg Plus IPR	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	Potassium	1.950 hours
GSK961081 1200 mg Plus IPR	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	QTcF	2.100 hours
GSK961081 1200 mg Plus IPR	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	QTcB	2.100 hours
GSK961081 1200 mg Plus IPR	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	Systlic BP	2.100 hours
GSK961081 1200 mg Plus IPR	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	Glucose	0.967 hours
GSK961081 1200 mg Plus IPR	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	Heart rate	1.517 hours
GSK961081 1200 mg Plus IPR	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	Diastolic BP	0.933 hours
GSK961081 400 mg Plus Placebo	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	QTcB	2.100 hours
GSK961081 400 mg Plus Placebo	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	Potassium	1.942 hours
GSK961081 400 mg Plus Placebo	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	Glucose	1.150 hours
GSK961081 400 mg Plus Placebo	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	Heart rate	1.567 hours
GSK961081 400 mg Plus Placebo	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	QTcF	2.133 hours
GSK961081 400 mg Plus Placebo	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	Systlic BP	2.008 hours
GSK961081 400 mg Plus Placebo	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	Diastolic BP	1.983 hours
GSK961081 1200 mg Plus Placebo	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	Glucose	0.967 hours
GSK961081 1200 mg Plus Placebo	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	QTcB	2.100 hours
GSK961081 1200 mg Plus Placebo	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	Potassium	1.933 hours
GSK961081 1200 mg Plus Placebo	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	Heart rate	1.567 hours
GSK961081 1200 mg Plus Placebo	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	Systlic BP	3.008 hours
GSK961081 1200 mg Plus Placebo	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	Diastolic BP	0.925 hours
GSK961081 1200 mg Plus Placebo	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	QTcF	2.117 hours

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

Time frame: Up to 82 days

Population: 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.

Arm	Measure	Value (MEDIAN)
GSK961081 400 mg Plus SAL	Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	0.920 Hours
GSK961081 1200 mg Plus SAL	Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	0.930 Hours
GSK961081 400 mg Plus IPR	Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	0.925 Hours
GSK961081 1200 mg Plus IPR	Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	0.920 Hours
GSK961081 400 mg Plus Placebo	Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	0.920 Hours
GSK961081 1200 mg Plus Placebo	Time to Maximum Plasma Concentration (Tmax) of GSK961081 Over Period Determined Directly From the Concentration-time Data	0.920 Hours

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.

Time frame: From dosing until 4 hours (0-4h)

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

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours	0.52 Beats per minute	Standard Error 0.729
GSK961081 1200 mg Plus SAL	Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours	1.77 Beats per minute	Standard Error 0.713
GSK961081 400 mg Plus IPR	Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours	-2.93 Beats per minute	Standard Error 0.714
GSK961081 1200 mg Plus IPR	Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours	-1.27 Beats per minute	Standard Error 0.72
GSK961081 400 mg Plus Placebo	Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours	-3.57 Beats per minute	Standard Error 0.721
GSK961081 1200 mg Plus Placebo	Weighted Mean Change From Baseline (Pre-dose on Day 1) in Heart Rate in Supine Position From 0 to 4 Hours	-2.21 Beats per minute	Standard Error 0.745

Comparison: GSK961081 400 mcg plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [2.456, 5.732]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-0.967, 2.258]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [2.324, 5.636]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-0.735, 2.603]

Secondary

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

Time frame: From dosing until 4 hours (0-4h)

Population: Modified Per Protocol population.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours	5.27 msec	Standard Error 1.569
GSK961081 1200 mg Plus SAL	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours	9.08 msec	Standard Error 1.542
GSK961081 400 mg Plus IPR	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours	0.08 msec	Standard Error 1.542
GSK961081 1200 mg Plus IPR	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours	4.44 msec	Standard Error 1.55
GSK961081 400 mg Plus Placebo	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours	0.07 msec	Standard Error 1.555
GSK961081 1200 mg Plus Placebo	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(B) in Supine Position From 0 to 4 Hours	6.12 msec	Standard Error 1.602

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [1.857, 8.542]

Comparison: GSK961081 400 mcg Plus IPR versus GSK961081 400 mcg plus Placebo during 0-4 hours95% CI: [-3.294, 3.307]

Comparison: GSK961081 1200 mcg Plus SAL versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-0.433, 6.345]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo during 0-4 hours95% CI: [-5.076, 1.711]

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.

Time frame: From dosing until 4 hours (0-4h)

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

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
GSK961081 400 mg Plus SAL	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours	5.42 msec	Standard Deviation 1.565
GSK961081 1200 mg Plus SAL	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours	7.53 msec	Standard Deviation 1.536
GSK961081 400 mg Plus IPR	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours	4.59 msec	Standard Deviation 1.535
GSK961081 1200 mg Plus IPR	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours	6.23 msec	Standard Deviation 1.546
GSK961081 400 mg Plus Placebo	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours	4.17 msec	Standard Deviation 1.549
GSK961081 1200 mg Plus Placebo	Weighted Mean Change From Baseline (Pre-dose on Day 1) in QTc(F) in Supine Position From 0 to 4 Hours	8.18 msec	Standard Deviation 1.597

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo over 0-4 hours95% CI: [-2.069, 4.566]

Comparison: GSK961081 400 mcg Plus SAL versus GSK961081 400 mcg plus Placebo over 0-4 hours95% CI: [-2.85, 3.687]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo over 0-4 hours95% CI: [-4.013, 2.714]

Comparison: GSK961081 1200 mcg Plus IPR versus GSK961081 1200 mcg plus Placebo over 0-4 hours95% CI: [-5.325, 1.427]

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

An Investigation Of The Interaction Of GSK961081 With Inhaled Beta-Agonist And Anti-Muscarinic Drugs.

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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.

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

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

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.

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

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

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

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

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

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

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

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

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

Number of Participants With Adverse Events and Serious Adverse Events

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

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

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

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

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

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

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

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