A Study to Assess the Effectiveness and Side Effects of G... | NCT03372603

NCT03372603

ID	Type	Description	Link
2017-002265-21	EudraCT Number

Status Module

Sponsor/Collaborators Module

Name	Class
Biomedical Advanced Research and Development Authority	FED

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment Sequence AB	Experimental	Subjects will receive GSK2798745 matching placebo tablets (two tablets on Day 1 followed by one tablet once daily for 6 days), via oral route (treatment period of total 7 days). After a washout period of 14 to 21 days, subjects will then receive 4.8 mg (two tablets of 2.4 mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 tablets once daily for 6 days via oral route (treatment period of total 7 days).	Drug: GSK2798745 Drug: Placebo
Treatment Sequence BA	Experimental	Subjects will receive 4.8 mg (two tablets of 2.4 mg) GSK2798745 on Day 1, followed by 2.4 mg GSK2798745 tablets once daily for 6 days via oral route (treatment period of total 7 days). After a washout period of 14 to 21 days, subjects will then receive GSK2798745 matching placebo tablets (two tablets on Day 1 followed by one tablet once daily for 6 days), via oral route (treatment period of total 7 days).	Drug: GSK2798745 Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GSK2798745	Drug	GSK2798745 tablets will be available as white to almost white, round, film-coated tablets (micronized active pharmaceutical ingredient [API]) to be taken with a glass of water (approximately 240 mL).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Total Cough Counts During Day Time Hours Following 7-days of Dosing	Coughs were monitored using the VitaloJAK cough monitor. The total cough counts during day-time (10 hours) was calculated from the time of the monitor being attached i.e. immediately after dosing on Day 7 to 10 hours past the time of monitoring. Total cough counts were log-transformed prior to analysis. A non-informative prior was used. Analysis was performed using a Bayesian mixed model adjusting for subject-level and period-adjusted baselines, treatment and period. Subject-level baseline is defined as the mean of the two period-specific baselines. Period-adjusted baseline is defined as the difference between the period-specific baseline and subject-level baseline for each period. Posterior median and 95% credible interval is reported. All Subjects Population included all randomized participants who took at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.	Up to 10 hours post-dose on Day 7 of each treatment period

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age between 18 and 75 years of age inclusive, at the time of signing the informed consent.
Chronic idiopathic cough for >=1 year (before screening), defined as: a cough that is unresponsive to at least 8 weeks of targeted treatment, or a cough for which no objective evidence of an underlying trigger has been determined, despite medical investigations.
No significant findings on chest imaging (chest X-ray [CXR] or Computed tomography scan) within 12 months before screening (subjects with an abnormal CXR within 12 months, from a temporary process, will be allowed to participate if a repeat CXR is normal).
Forced expiratory volume in one second (FEV1) >=80% of the predicted normal value (at screening), or documented evidence of FEV1 >=80% within the 6 months before screening.
Score of >=40 millimeters (mm) on the Cough Severity Visual Analogue Scale (VAS) at Screening.
Body weight >=50 kilogram (kg) and body mass index (BMI) within the range 18 to 40 kilogram per meter square (kg/m^2) (inclusive) at screening.
A male participant must agree to follow the contraception requirements stated in the protocol from the time of first dose of study treatment until 2 weeks after last dose of study treatment, and refrain from donating sperm during this period.
A female participant is eligible to participate if she is not of childbearing potential.
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

History or current evidence of any serious or clinically significant gastrointestinal, renal, endocrine, neurologic, hematologic or other condition that is uncontrolled on permitted therapies or that would, in the opinion of the investigator or the medical monitor, make the subject unsuitable for inclusion in this study.
History or current evidence of chronic productive cough.
History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the 6 months before screening.
Active ulcer disease or gastrointestinal bleeding at the time of screening (positive fecal occult blood test [FOBT] at screening).
History of stroke or seizure disorder within 5 years of screening.
Respiratory tract infection within 6 weeks of screening.
Subject who, in the investigator's opinion, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behavior and/or any evidence of suicidal ideation on any questionnaires e.g. Type 4 or 5 on the Columbia Suicidality Severity Rating Scale (C-SSRS) in the last 6 months (assessed at screening).
Alanine transferase (ALT) > twice the upper limit of normal (ULN) at screening.
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at screening.
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
QT interval corrected (QTc) >450 milliseconds (msec) or QTc >480 msec in subjects with bundle branch block at screening.
Use of a listed prohibited medication within the restricted timeframe relative to the first dose of study treatment.
Use of a strong inhibitors or inducers of cytochrome P450 (CYP) 3A or pglycoprotein.
Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 3 months of screening.
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Current enrollment or past participation within the 3 months before screening in any clinical study involving an investigational study treatment or any other type of medical research.
Positive human immunodeficiency virus (HIV) antibody test at screening.
Presence of Hepatitis B surface antigen (HBsAg) at screening.
Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment.
Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
Cardiac troponin at screening > ULN for the assay.
History of alcohol abuse within 6 months of screening, in the opinion of the investigator.
Current smoker or history of smoking within the 6 months before screening, or a cumulative history of >= 20 pack years. Pack years = (Number of cigarettes smoked/day/20) x (Number of years smoked)
Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates participation in the study.

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director
GSK Clinical Trials	GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Manchester	Lancashire	M23 9LT	United Kingdom
GSK Investigational Site

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo/GSK2798745	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 of treatment period 1. In treatment period 2, participants received two tablets of 2.4 milligrams (mg) GSK2798745 each on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 25, 2018	Aug 20, 2019

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Treatment Sequence AB
Treatment Sequence BA

FG0009 subjects
FG0018 subjects

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	All Study Participants	All participants who were randomized to either of the two treatment sequences Placebo/GSK2798745 and GSK2798745/Placebo and received GSK2798745 and placebo in either Treatment period 1 or 2 were included. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00061.0± 9.85

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00015
Male	BG0002

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

Asian-Japanese/East Asian (EA)/South EA Heritage

Title	Measurements
	BG0001

White

Title	Measurements
	BG000

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Total Cough Counts During Day Time Hours Following 7-days of Dosing

Coughs were monitored using the VitaloJAK cough monitor. The total cough counts during day-time (10 hours) was calculated from the time of the monitor being attached i.e. immediately after dosing on Day 7 to 10 hours past the time of monitoring. Total cough counts were log-transformed prior to analysis. A non-informative prior was used. Analysis was performed using a Bayesian mixed model adjusting for subject-level and period-adjusted baselines, treatment and period. Subject-level baseline is defined as the mean of the two period-specific baselines. Period-adjusted baseline is defined as the difference between the period-specific baseline and subject-level baseline for each period. Posterior median and 95% credible interval is reported. All Subjects Population included all randomized participants who took at least 1 dose of study treatment. Participants were analyzed according to the treatment they actually received.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Median

95% Confidence Interval

Cough counts

Up to 10 hours post-dose on Day 7 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Units	Counts
Participants	OG00017 OG00115

Title

Denominators

Categories

Title	Measurements
	OG000180.570(137.852 to 235.446) OG001241.105(181.383 to 320.600)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Ratio	1.336			2-Sided	90	0.965	1.847			Treatment comparison ratio of GSK2798745 and placebo using posterior median ratio and 90% credible interval is presented.		Other

Secondary

Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgment.

All Subjects Population.

Posted

Count of Participants

Participants

Up to 45 days

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Amino Transferase (AST) and Creatinine Kinase (CK)

Blood samples were collected for the analysis of clinical chemistry parameters including ALP, ALT, AST and CK. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day -1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Clinical Chemistry Parameter: Direct Bilirubin, Total Bilirubin and Creatinine

Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, total bilirubin and creatinine. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day -1) and Day 8 for each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Clinical Chemistry Parameters: Calcium, Glucose, Potassium, Sodium and Urea

Blood samples were collected for the analysis of clinical chemistry parameters including calcium, glucose, potassium, sodium and urea/blood urea nitrogen (BUN). Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day -1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Clinical Chemistry Parameter: Total Protein

Blood samples were collected for the analysis of clinical chemistry parameter total protein. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day -1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Number of Participants With Abnormal Values of Cardiac Troponin

Cardiac troponin values was measured in participants.

All Subjects Population.

Posted

Count of Participants

Participants

Up to 45 days

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Units	Counts
Participants	OG000

Secondary

Change From Baseline Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count and White Blood Cell (WBC) Count

Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, total neutrophils, platelet count and WBC count. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Giga units per liter

Baseline (Day -1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Hematology Parameter: Hemoglobin

Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day -1) and Day 8 for each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Hematology Parameter: Hematocrit

Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Percentage of red blood cells in blood

Baseline (Day -1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)

Blood samples were collected for the analysis of hematology parameter: MCH. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Picograms

Baseline (Day -1) and Day 8 for each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Hematology Parameter: Mean Corpuscular Volume (MCV)

Blood samples were collected for the analysis of hematology parameter: MCV. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Femtoliters

Baseline (Day -1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Hematology Parameter: Red Blood Cell (RBC) Count

Blood samples were collected for the analysis of hematology parameter: RBC count. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Tera units per liter

Baseline (Day -1) and Day 8 for each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline Values for Hematology Parameter: Reticulocytes

Blood samples were collected for the analysis of hematology parameter: reticulocytes. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Percentage of reticulocytes in blood

Baseline (Day -1) and Day 8 for each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Number of Participants With Abnormal Urinalysis Data

Urine samples were collected for analysis of urinalysis data by dipstick method. Number of participants with abnormal urinalysis data has been presented. Abnormality was defined as value of potential clinical importance (PCI). PCI was flagged when a result changed from negative on Day 1 (pre-dose) to positive on Day 8.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Count of Participants

Participants

Up to Day 8

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

Blood pressure was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (pre-dose on Day 1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline in Temperature

Temperature was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (pre-dose on Day 1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Change From Baseline in Heart Rate

Heart rate was measured at indicated time points in supine position after 5 minutes rest for the participant. Baseline was defined as latest pre-dose assessment with a non-missing value in each treatment period. Change from Baseline was calculated as the value at the post-dose visit minus the Baseline value.

All Subjects Population. Only those participants with data available at the specified data points were analyzed.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (pre-dose on Day 1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Secondary

Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Twelve-lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT (QTc) intervals. Number of participants with abnormal-clinically significant and abnormal-not clinically significant values has been presented.

All Subjects Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category title).

Posted

Count of Participants

Participants

Baseline (pre-dose on Day 1) and Day 8 of each treatment period

ID	Title	Description
OG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.
OG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants were administered two tablets of placebo on Day 1 followed by one tablet of placebo on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.	0	17	0	17	9	17
EG001	GSK2798745	Participants were administered two tablets of 2.4 mg GSK2798745 on Day 1 followed by one tablet of 2.4 mg GSK2798745 on Days 2 to 7 in either treatment period 1 or 2. All doses were administered once daily via the oral route with a glass of water. The treatment periods were separated by a wash-out period of 14 to 21 days.	0	16	0	16	11	16

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0003 events3 affected17 at risk EG0017 events7 affected16 at risk
Lethargy	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Migraine	Nervous system disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0011 events1 affected16 at risk
Vomiting	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected16 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Gastroenteritis	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Irritable bowel syndrome	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Toothache	Gastrointestinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Ear pruritus	Ear and labyrinth disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Hypoacusis	Ear and labyrinth disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Fatigue	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0012 events2 affected16 at risk
Feeling cold	General disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Suprapubic pain	General disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0002 events2 affected17 at risk EG0010 events0 affected16 at risk
Nasal pruritus	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Visual impairment	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0011 events1 affected16 at risk
Eye pain	Eye disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Oral herpes	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Sinus bradycardia	Cardiac disorders	MedDRA 21.1	Systematic Assessment	EG0000 events0 affected17 at risk EG0011 events1 affected16 at risk
Contusion	Injury, poisoning and procedural complications	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk
Sleep disorder	Psychiatric disorders	MedDRA 21.1	Systematic Assessment	EG0001 events1 affected17 at risk EG0010 events0 affected16 at risk

ID	Term
D003371	Cough
D000096822	Chronic Cough

ID	Term
C000656065	GSK2798745

Units	Counts
Participants	OG00017 OG00114

Units	Counts
Participants	OG00017 OG00114

Units	Counts
Participants	OG00017 OG00115

Units	Counts
Participants	OG00017 OG00116

ID	Term
D012120	Respiration Disorders
D012140	Respiratory Tract Diseases
D012818	Signs and Symptoms, Respiratory
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms