Cough
Conditions
Keywords
efficacy, hypertussive challenge, voltage gated sodium channels (VGSC), anaesthesia, Safety and tolerability, capsaicin challenge, cough, citric acid challenge, pharmacokinetics
Brief summary
This study is designed to evaluate the effect of GSK2339345 relative to placebo on the number of coughs in patients with Chronic Idiopathic Cough (CIC) administered by an Aqueous Droplet Inhaler (ADI). The primary aim is to investigate the efficacy of GSK2339345 on reducing objective cough frequency in CIC patients. The secondary aim of this study is to investigate the efficacy of GSK2339345 in inhibiting a hypertussive cough response elicited by capsaicin and citric acid in CIC patients which have a hyperresponsive cough reflex. Following the screening visit, all eligible subjects will attend the unit for dosing at Visits 1-7. At Visits 1, 2 and 3 (Part A of the study), subjects will receive two doses of either GSK2339345 or placebo, 4 hours apart and will undergo 8 hours of cough monitoring. At Visits 4 and 5 (Part B of the study) and Visits 6 and 7 (Part C of the study), subjects will be administered a single dose of either GSK2339345 or placebo. Subjects will then undergo capsaicin (Part B) or citric acid (Part C) tussive challenge and will undergo cough monitoring for 1 hour post dose. The maximum study duration will be approximately 11 weeks, including 3 weeks screening and 2 weeks follow-up. Approximately 30 patients will be randomised into the study, such that approximately 24 patients complete dosing and critical assessments.
Interventions
DRUGGSK2339345
Clear colorless solution in clear glass vial for oral inhalation via aqueous droplet inhaler with unit dose strength of 1000 microgram (mcg) inhaled in two actuations.
DRUGPlacebo
Clear colorless solution of 0.9% sodium chloride for oral inhalation via aqueous droplet inhaler inhaled in two actuations.
Sponsors
North West Lung Centre
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic Idiopathic Cough patients according to the criteria listed below, determined by a responsible and experienced physician, based on a medical evaluation: Idiopathic cough defined as chronic cough resistant to treatment targeted at potential triggers. Chronic cough defined as cough lasting for more than 8 weeks. * A patient with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Male/females aged \>=18 years old, at the time of signing the informed consent. * Non-smoker for at least 6 months with a cumulative history of \<= 10 pack years. Pack years = (No. of cigarettes smoked/day/20) x (No. of years smoked). * Body weight \>= 50 kilograms. * A female subject is eligible to participate if she is of; Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy \[for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records\]; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone \> 40 milli international unit/milliliter (mL) and estradiol \< 40 picogram/ml (\<147 picomoles/Liter \[L\]) is confirmatory\]. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 to4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method. Child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotropin test at screening or prior to dosing and Agrees to use one of the contraception methods for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until the follow up visit or has only same-sex partners, when this is her preferred and usual lifestyle. * Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication until the follow up visit. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Aspartate amino transferase and alanine amino transferase \< 2xupper limit of normal (ULN); alkaline phosphatase and bilirubin \<= 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). * Based on averaged QT interval corrected (QTc) values of triplicate electrocardiograms (ECGs) obtained over a brief recording period: QTc using Fridericia's formula (QTcF) \< 450 millisecond. * A 24 hour Holter ECG at screening that demonstrates no clinically significant abnormalities or finding that could interfere with interpretation of the study results, when assessed by an appropriately trained and experienced reviewer.
Exclusion criteria
Based Upon Medical Histories * Subjects who have evidence of current asthma, as confirmed by the Investigator or designee. * Subjects with any clinically significant respiratory condition or lung pathology that could cause cough (apart from chronic idiopathic cough). * Known lung cancer or other active malignancy, or history of. * Subjects with current or a chronic history of cardiovascular disease (including uncontrolled hypertension, ischemic heart disease, angina, myocardial infarct, congestive heart failure, and stroke). * Subjects with current central nervous system / peripheral nervous system conditions e.g. epilepsy and myasthenia gravis. * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Any subject with a respiratory tract infection within 4 weeks of screening. * Radiological imaging prior to the study, including chest X-rays, that have shown any evidence of clinically significant lung disease, as judged by the Investigator or designee. * History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of \>21 units for males or \>14 units for females. One unit is equivalent to 8 grams of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits. * Any subject who has a history of an allergic reaction to a local anesthetic. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation. * Any subject who has a known hypersensitivity to capsaicin or citric acid.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Cough Count Over 8 Hours at Visits 1, 2 and 3 (Part A) | Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A) | Total cough count (8 hours \[hr\] of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first four hours starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Number of coughs in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts recorded post dose of every treatment i.e. placebo or GSK2339345 1000mcg was reported. |
| Total Cough Count Excluding Transient Coughs Over 8 Hours at Visits 1, 2 and 3 (Part A) | Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A) | Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first 4-hrs starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Transient cough was the total number of coughs experienced in the two mins from the start of the first inhalation of a dose. Number of coughs excluding transient cough in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts excluding transient cough recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | Pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr post each dose administered in Parts A, B and C (up to 8 weeks) | Systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were obtained at following time points: pre-dose, 5 minutes (min), 15 min (only in Part A), 30 min, and 1 hr after first administration (FA) and second administration (SA) in Part A and each dose administration of Parts B and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. Pre-Dose is the average (avg) of the triplicate readings taken at the pre-dose assessment. |
| Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr after each dose administered in Parts A, B and C (up to 8 weeks) | Heart rate measurements were obtained at following time points: pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr after FA and SA in Part A and each dose administration in Parts B and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. Pre-Dose is the average of the triplicate readings taken at the pre-dose assessment. |
| Mean Body Temperature at the Indicated Time Points in Parts A, B and C | 1 hr post the second dose administered in Part A and 1 hr post each dose administered in Parts B and C (up to 8 Weeks) | Body temperature measurements were obtained at1 hr post-dose 2 FA and SA in Part A and each administration in Parts B, and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Pre-dose and 5min to 1 hr after each dose administered in Parts A, B and C (up to 8 Weeks) | A 12-lead ECG was recorded in a seated position after the participant was kept at rest in this position for at least 10 minutes. ECGs were obtained at pre-dose and 5 min, 15 min (only in Part A) 30 min, and 1 hr after FA and SA in Part A and each administration in Parts B, and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. Data are presented as clinically significant (CS) or not clinically significant (NCS) abnormal findings any time during study. The study investigator determined if the abnormal ECG finding was CS or NCS. |
| Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC - absolute neutrophil count), platelet count, and white blood cells count at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Mean Hematocrit Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of hematocrit at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of mean corpuscle hemoglobin at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Mean Corpuscle Volume Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of mean corpuscle volume at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A |
| Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of red blood cell count at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of ALP, ALT, AST and GGT at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement ofdirect bilirubin, total bilirubin, creatinine and uric acid at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of calcium, chloride, glucose, potassium, sodium, and urea/blood urea nitrogen (BUN) at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Mean Troponin I Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of troponin I at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. Cardiac troponin values that were below the quantification limit \[0.02 or 0.04 microgram (mcg/L)\] were imputed as 0.01 (mcg/L). |
| Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Pre-dose and 30 min post each dose administered in Parts A, B and C (up to 8 Weeks) | Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured by spirometry at pre-dose and 30 min after FA and SA in Part A and each administration in Parts B, and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | From 2 min -2 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 8 weeks) | The perception of change in oropharyngeal sensation was assessed by a 4 point scale where participants were asked to describe sensitivity and perception of numbness and the responses were recorded. The following information was collected: 0 = no anaesthesia (A), 1 = mild anaesthesia, 2 = moderate anaesthesia and 3 = severe anaesthesia. Oropharyngeal examination was performed at 2 min, 5 min, 15 min, 30 min, 1 hr and 2 hr after FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A |
| Mean Transient Cough Counts at the Indicated Time Points in Part A | 0-4 hr, 4-8 hr, 0-8 hr post each dose at Visits 1, 2 and 3 in Part A (up to 8 weeks) | Cough counts (8 hours of recording) was conducted at Visits 1, 2 and 3 (4 hours of post-dose recording for each of the two doses administered). Coughs was counted by a cough monitor fitted to the participants for 8 hours post Dose 1. Transient coughing was calculated as the total number of coughs experienced in the two minutes from the start of the first inhalation of a dose. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A |
| Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks) | Blood samples were collected for the measurement of hemoglobin, MCHC, albumin and total protein at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses | From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks) | AUC curve from time zero (pre-dose) to 1 hours AUC(0-1) and from time zero to the last time AUC(0-t) of quantifiable concentration of GSK2339345 following the first dose and second dose at each visit in Part A was measured. Samples were collected at the following time points: pre-dose; 2 min, 5 min, 10 min, 30 min, 1 hr and 2hr (only after Dose 1) post every dose administration at Visits 1, 2 and 3. For , AUC(0-1) and AUC(0-t), non calculable (NC) were imputed prior to derivation of summary statistics and NCs were imputed as 0.1093 and 0.0855 respectively (=half the lowest observed value). |
| Maximum Observed Concentration (Cmax) of GSK2339345 Following Two Repeated Doses | From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks) | Cmax is defined as the maximum observed concentration of GSK2339345 following two repeated doses at each visit in Part A. Samples were collected at the following time points: pre-dose; 2 min, 5 min, 10 min, 30 min, 1 hr and 2hr (only after Dose 1) post every dose administration at Visits 1, 2 and 3. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. For Cmax, NCs were imputed prior to derivation of summary statistics and NCs were imputed with 0.5\*LLQ (LLQ=0.20 ng/mL). |
| Time to Reach the Observed Maximum Concentration (Tmax) of GSK2339345 Following Two Repeated Doses | From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks) | Tmax is defined as the time to reach the observed maximum GSK2339345concentration following two repeated doses at each visit in Part A. Samples were collected at the following time points: pre-dose; 2 min, 5 min, 10 min, 30 min, 1 hr and 2hr (only after Dose 1) post every dose administered at Visits 1, 2 and 3. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. |
| Mean Cough Count Over 4 Hours at Visits 1, 2 and 3 (Part A) | Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A) | Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3 (4- hrs of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count over 4-hrs was done by using the sum of first 4-hrs starting from the time of first dose and the second 4-hrs starting at the time of the second dose respectively. Number of coughs in 0-4 hr and 4-8 hr period was log-e transformed and used for the analysis. Values were imputed pro-rata if 4 hr epoch was less than 4 hr. Mean of the total cough counts over 4-hrs recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported. |
| Total Cough Count Excluding Transient Coughs Over 4 Hours at Visits 1, 2 and 3 (Part A) | Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A) | Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3 (4-hrs of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. Total count excluding transient cough over 4-hrs was done by using the sum of first 4-hrs starting from the time of first dose and the second 4-hrs starting at the time of the second dose respectively. Number of coughs excluding transient cough in 0-4 hr and 4-8 hr period was log-e transformed and used for the analysis. Values were imputed pro-rata if 4-hr epoch was less than 4-hrs. Mean of the total cough counts over 4-hrs recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported. |
| Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | Up to 8 hours post-dose at Visits 1, 2 and 3 in Part A (up to 3 weeks) | Cough counts (8 hr of recording) were conducted at Visits 1, 2 and 3 (4-hr of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participant for 8 hr post Dose 1. The first epoch started at the time of the first dose, and the 60 min time periods continued until an epoch ended immediately before the second dose (or 4-hr after the first dose if earlier). The epochs were then re-started at the start of the second dose at 60 min intervals, finishing with an epoch which ran to 4-hrs after the start of the second dose. The cough counts were sum-up by the treatments received by the participants. Mean cough count was calculated per participant if the same treatment was taken during different periods. Values were imputed pro-rata if 1 hr epoch is less than 60 min. |
| Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | Up to 8 hours post-dose in Visits 1, 2 and 3 in Part A (up to 3 weeks) | Cough counts (8 hr of recording) were conducted at Visits 1, 2 and 3 (4-hr of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participant for 8 hr post Dose 1. The first epoch started at the time of the first dose, and the 30 min time periods continued until an epoch ended immediately before the second dose (or 4-hr after the first dose if earlier). The epochs were then re-started at the start of the second dose at 30 min intervals, finishing with an epoch which ran to 4-hr after the start of the second dose. The cough counts were sum-up by the treatments received by the participants. Mean cough count was calculated per participant if the same treatment was taken during different periods. |
| Mean Cough Counts by 15 Min Epoch in Part A | Up to 8 hours post-dose at Visits 1, 2 and 3 in Part A (up to 3 weeks) | Cough counts (8 hr of recording) were conducted at Visits 1, 2 and 3 (4-hr of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participant for 8 hr post Dose 1. The first epoch started at the time of the first dose, and the 15 min time periods continued until an epoch ended immediately before the second dose (or 4h after the first dose if earlier). The epochs were then re-started at the start of the second dose at 15 min intervals, finishing with an epoch which ran to 4-hr after the start of the second dose. The cough counts were sum-up by the treatments received by the participants. Mean cough count was calculated per participant if the same treatment was taken during different periods. |
| Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Prior to first dose and 1hr post second dose at Visits 1, 2 and 3 in Part A (up to 3 weeks) | VAS for urge to cough and severity of cough were recorded prior to first dose and 1 hour following the second dose of GSK2339345 or placebo at Visits 1, 2 and 3.VAS is a 100-mm linear scales on which participants indicated the severity of their cough (0 mm represents no severity and 100 mm maximum severity ever experienced) and urge to cough (0 represents no urge to cough, 100 represents maximum urge to cough ever experienced). Mean of replicate values per participants used where the same treatment taken during different periods. |
| Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | After the administration of GSK2339345 or placebo (first and second 15 seconds following each dose) at Visits 4 and 5 in Part B (up to 2 weeks) | Capsaicin was administered using a dosimeter through a nebulizer pot with flow-limitation. Inhalation of increased concentrations (Conc.) was continued until the maximum dose was tolerated by the par. or highest available Conc. was used. The dose-response relationship between dose of capsaicin and cough response was investigated using non-linear mixed effect modeling using Poisson and Negative Binomial distributions. When using a Poisson distribution, there was some evidence for a reduction in capsaicin Emax with GSK2339345 of 17.6%, however, this was not confirmed when using a Negative Binomial distribution. The Negative Binomial distribution described the data marginally better, but the dataset was too small to make definitive conclusions. There was no treatment difference in capsaicin ED50. |
| Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | After the administration of GSK2339345 or placebo (first and second 15 seconds following each dose) at Visits 6 and 7 in Part C (up to 2 weeks) | Citric acid was administered using a dosimeter through a nebulizer pot with flow-limitation. Inhalation of increased Conc. was continued until the maximum dose was tolerated by the par. or the highest available Conc. was used. The dose-response relationship between the dose of citric acid and cough response was investigated using non-linear mixed effect modelling using Poisson and Negative Binomial distributions. When using a Poisson distribution, there was some evidence for an increase in citric acid ED50 with GSK2339345 of 41.6%, however, this was not confirmed when using a Negative Binomial distribution. The Negative Binomial distribution described the data marginally better, but the dataset was too small to make definitive conclusions. There was no treatment difference in citric acid Emax |
| CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | After the administration of GSK2339345 or placebo at Visits 4 and 5 in Part B (up to 2 weeks) | CC was performed following the administration of GSK2339345 or placebo at Visits 4 and 5. Capsaicin was administered using a dosimeter through a nebulizer. The number of coughs in the first and second 15 sec following each dose of CC agent were recorded. Inhalation of increased conc. was continued until the maximum dose was tolerated by the participant or the highest available conc. was used. CC agent dose concentration required to achieve C2 (2 coughs were first observed \[FO\]), C5 (5 coughs were FO) and C6 (6 coughs were FO) are presented. All instances of missing values occurred where a participant did not achieved the required number of coughs for a parameter. |
| CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | After the administration of GSK2339345 or placebo at Visits 6 and 7 in Part C (up to 2 weeks) | CAC was performed following the administration of GSK2339345 or placebo at Visits 6 and 7. CA was administered using a dosimeter through a nebulizer pot with flow-limitation. Number of coughs in the first and second 15 sec following each dose of CAC agent were recorded. Inhalation of increased conc. was continued until the maximum dose was tolerated by the participants or the highest available Conc. was used. CAC agent dose concentration required to achieve C2 (2 coughs were first observed \[FO\]), C5 (5 coughs were FO) and C6 (6 coughs were FO) are presented. All instances of missing values occurred where a participant did not achieved the required number of coughs for a parameter. |
| CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | After the administration of GSK2339345 or placebo at Visits 4 and 5 in Part B (up to 2 weeks) | CC was performed following the administration of GSK2339345 or placebo at Visits 4 and 5. Capsaicin was administered using a dosimeter through a nebulizer. The number of coughs in the first and second 15 sec following each dose of CC agent were recorded. Inhalation of increased Conc. was continued until the maximum dose was tolerated by the participant or the highest available Conc. was used. CC agent imputed dose concentration required to achieve C2 (at which 2 coughs were first observed \[FO\]), C5 (at which 5 coughs were FO) and C6 (at which 6 coughs were FO) are presented. For participants who did not complete the challenge and not reached the endpoint, values were imputed to the next dose in the challenge sequence after stopping. For participants who completed the challenge and had not reached the endpoint, values were imputed to 2000 (=twice the highest dose of capsaicin). |
| CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | After the administration of GSK2339345 or placebo at Visits 6 and 7 in Part C (up to 2 weeks) | CAC was performed following the administration of GSK2339345 or placebo at Visits 6 and 7. CA was administered using a dosimeter through a nebulizer pot with flow-limitation. Number of coughs in the first and second 15 sec following each dose of CAC agent were recorded. Inhalation of increased Conc. was continued until the maximum dose was tolerated by the participants or the highest available Conc. was used. CAC agent imputed dose concentration required to achieve C2 (at which 2 coughs were first observed \[FO\]), C5 (at which 5 coughs were FO) and C6 (at which 6 coughs were FO) are presented. For participants who did not complete the challenge and not reached the endpoint, values were imputed to the next dose in the challenge sequence after stopping. For participants who completed the challenge and had not reached the endpoint, values were imputed to 2000 (=twice the highest dose of CA). |
| Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks) | Plasma concentrations of GSK2339345 following the first dose and second dose at each visit in Part A was measured. Samples were collected at the following time points: pre-dose, 2 min, 5 min, 10 min, 30 min, 1 hr and 2 hr (only after Dose 1) after each dose administration at Visits 1, 2 and 3. All non-quantifiable (NQ) values after the pre-first dose value imputed to half lower limit of quantification (LLQ) (LLQ=0.2 nanogram per milliliter \[ng/mL\]). Different participants may have been analyzed for different parameters, so the overall number of par. analyzed reflects everyone in the pharmacokinetic population. |
| Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | From the start of study treatment and until the follow-up contact (up to 8 Weeks) | An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury. |
Countries
United Kingdom
Participant flow
Pre-assignment details
All eligible participants (par.) received treatment of either GSK2339345 or placebo at each visit in Parts A (Visits 1-3), B (Visits 4 and 5) and Part C (Visits 6 and 7).
Participants by arm
| Arm | Count |
|---|---|
| GSK2339345 1000 µg/Placebo Participants received two doses of either GSK2339345 1000 µg or matching placebo as a solution administered via an ADI with a four hour dosing interval at 3 visits (one treatment per visit) in Part A and a single dose at 2 visits (one treatment per visit) in Part B and C. Dose 1 was administered on each treatment day at the same time each morning throughout all of Parts A, B and C. The follow-up of each participant occurred 3-14 days after the last dose. There was a washout of 48 hours to 7 days between visits. Additionally, 5 minutes after the administration of placebo or GSK2339345 at each visit period in Part B and C, participants received an oral inhalation of 10 µL of a capsaicin solution at each visit in Part B and 10 µL of a citric acid solution at each visit of Part C. The strength of capsaicin solution ranged from 0.49 to 1000 µM and the citric acid solution strength ranged from 0.03 to 4.0 molar. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Part A | Adverse Event | 2 |
| Part A | Withdrawal by Subject | 1 |
| Part B | Adverse Event | 1 |
| Part B | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | GSK2339345 1000 µg/Placebo |
|---|---|
| Age, Continuous | 56.7 Years STANDARD_DEVIATION 9.58 |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 16 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 16 | 5 / 14 |
| serious Total, serious adverse events | 0 / 16 | 0 / 14 |
Outcome results
Primary
Total Cough Count Excluding Transient Coughs Over 8 Hours at Visits 1, 2 and 3 (Part A)
Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first 4-hrs starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Transient cough was the total number of coughs experienced in the two mins from the start of the first inhalation of a dose. Number of coughs excluding transient cough in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts excluding transient cough recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported.
Time frame: Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A)
Population: All Subjects Population. Only participants with at least one 8 hr cough count were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Cough Count Excluding Transient Coughs Over 8 Hours at Visits 1, 2 and 3 (Part A) | 151.5 Cough count | Standard Error 0.237 |
| GSK2339345 1000 Microgram (mcg) | Total Cough Count Excluding Transient Coughs Over 8 Hours at Visits 1, 2 and 3 (Part A) | 153.9 Cough count | Standard Error 0.237 |
90% CI: [0.87, 1.19]
Primary
Total Cough Count Over 8 Hours at Visits 1, 2 and 3 (Part A)
Total cough count (8 hours \[hr\] of recording) was conducted at Visits 1, 2 and 3. Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count was calculated as the sum of two four hour cough count totals, with the first four hours starting from the time of the first dose and the second four hours starting at the time of the second dose. The cough counts were sum-up by the treatments received by the participants. Number of coughs in 8 hr period was loge transformed and used for the analysis. Values were imputed pro-rata if 8 hr epoch was less than 8 hr. Mean of the total cough counts recorded post dose of every treatment i.e. placebo or GSK2339345 1000mcg was reported.
Time frame: Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A)
Population: All Subjects Population comprised of all participants who receive at least one dose of study medication. Only participants with at least one 8 hr cough count were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Cough Count Over 8 Hours at Visits 1, 2 and 3 (Part A) | 152.7 cough count | Standard Error 0.226 |
| GSK2339345 1000 Microgram (mcg) | Total Cough Count Over 8 Hours at Visits 1, 2 and 3 (Part A) | 192.5 cough count | Standard Error 0.226 |
90% CI: [1.1, 1.44]
Secondary
Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses
AUC curve from time zero (pre-dose) to 1 hours AUC(0-1) and from time zero to the last time AUC(0-t) of quantifiable concentration of GSK2339345 following the first dose and second dose at each visit in Part A was measured. Samples were collected at the following time points: pre-dose; 2 min, 5 min, 10 min, 30 min, 1 hr and 2hr (only after Dose 1) post every dose administration at Visits 1, 2 and 3. For , AUC(0-1) and AUC(0-t), non calculable (NC) were imputed prior to derivation of summary statistics and NCs were imputed as 0.1093 and 0.0855 respectively (=half the lowest observed value).
Time frame: From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks)
Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses | AUC(0-1), FA, Dose 1, n=11 | 0.3968 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 109.1924 |
| Placebo | Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses | AUC(0-1), FA, Dose 2, n=10 | 0.8168 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 76.8324 |
| Placebo | Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses | AUC(0-1), SA, Dose 1, n=7 | 0.4509 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 174.9418 |
| Placebo | Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses | AUC(0-1), SA, Dose 2, n=6 | NA hour*nanogram per milliliter (h*ng/mL) | — |
| Placebo | Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses | AUC(0-t), FA, n=14 | 2.0076 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 174.1325 |
| Placebo | Area Under the Concentration (AUC) Time (0-1) and AUC(0-t) of GSK2339345 Following Two Repeated Doses | AUC(0-t), SA, n=7 | 1.2425 hour*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 559.182 |
Secondary
CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C)
CAC was performed following the administration of GSK2339345 or placebo at Visits 6 and 7. CA was administered using a dosimeter through a nebulizer pot with flow-limitation. Number of coughs in the first and second 15 sec following each dose of CAC agent were recorded. Inhalation of increased conc. was continued until the maximum dose was tolerated by the participants or the highest available Conc. was used. CAC agent dose concentration required to achieve C2 (2 coughs were first observed \[FO\]), C5 (5 coughs were FO) and C6 (6 coughs were FO) are presented. All instances of missing values occurred where a participant did not achieved the required number of coughs for a parameter.
Time frame: After the administration of GSK2339345 or placebo at Visits 6 and 7 in Part C (up to 2 weeks)
Population: CAC population: Only those participants available at the specified time points were analyzed (represented by n=X,X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the CAC Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C2, 0-15 sec, n=8, 9 | 0.209 mol/L | Geometric Coefficient of Variation 111.073 |
| Placebo | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C2, 0-30 sec, n=8, 9 | 0.192 mol/L | Geometric Coefficient of Variation 113.563 |
| Placebo | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C5, 0-15 sec, n=7, 7 | 0.305 mol/L | Geometric Coefficient of Variation 138.956 |
| Placebo | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C5, 0-30 sec, n=7, 8 | 0.276 mol/L | Geometric Coefficient of Variation 101.609 |
| Placebo | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C6, 0-15 sec, n=7, 7 | 0.371 mol/L | Geometric Coefficient of Variation 158.73 |
| Placebo | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C6, 0-30 sec, n= 7, 8 | 0.336 mol/L | Geometric Coefficient of Variation 141.375 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C6, 0-15 sec, n=7, 7 | 0.743 mol/L | Geometric Coefficient of Variation 76.173 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C2, 0-15 sec, n=8, 9 | 0.156 mol/L | Geometric Coefficient of Variation 142.342 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C5, 0-30 sec, n=7, 8 | 0.707 mol/L | Geometric Coefficient of Variation 127.046 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C2, 0-30 sec, n=8, 9 | 0.156 mol/L | Geometric Coefficient of Variation 142.342 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C6, 0-30 sec, n= 7, 8 | 0.771 mol/L | Geometric Coefficient of Variation 98.463 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C5, 0-15 sec, n=7, 7 | 0.610 mol/L | Geometric Coefficient of Variation 90.153 |
Secondary
CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C)
CAC was performed following the administration of GSK2339345 or placebo at Visits 6 and 7. CA was administered using a dosimeter through a nebulizer pot with flow-limitation. Number of coughs in the first and second 15 sec following each dose of CAC agent were recorded. Inhalation of increased Conc. was continued until the maximum dose was tolerated by the participants or the highest available Conc. was used. CAC agent imputed dose concentration required to achieve C2 (at which 2 coughs were first observed \[FO\]), C5 (at which 5 coughs were FO) and C6 (at which 6 coughs were FO) are presented. For participants who did not complete the challenge and not reached the endpoint, values were imputed to the next dose in the challenge sequence after stopping. For participants who completed the challenge and had not reached the endpoint, values were imputed to 2000 (=twice the highest dose of CA).
Time frame: After the administration of GSK2339345 or placebo at Visits 6 and 7 in Part C (up to 2 weeks)
Population: CAC Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C2, 0-15 sec | 0.314 mol/L | Geometric Coefficient of Variation 279.912 |
| Placebo | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C2, 0-30 sec | 0.290 mol/L | Geometric Coefficient of Variation 294.833 |
| Placebo | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C5, 0-15 sec | 0.630 mol/L | Geometric Coefficient of Variation 410.643 |
| Placebo | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C5, 0-30 sec | 0.583 mol/L | Geometric Coefficient of Variation 379.787 |
| Placebo | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C6, 0-15 sec | 0.735 mol/L | Geometric Coefficient of Variation 387.993 |
| Placebo | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C6, 0-30 sec | 0.680 mol/L | Geometric Coefficient of Variation 387.993 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C6, 0-15 sec | 1.260 mol/L | Geometric Coefficient of Variation 179.623 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C2, 0-15 sec | 0.156 mol/L | Geometric Coefficient of Variation 142.342 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C5, 0-30 sec | 0.926 mol/L | Geometric Coefficient of Variation 185.962 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C2, 0-30 sec | 0.156 mol/L | Geometric Coefficient of Variation 142.342 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C6, 0-30 sec | 1.000 mol/L | Geometric Coefficient of Variation 152.443 |
| GSK2339345 1000 Microgram (mcg) | CAC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 6 and 7 (Part C) | C5, 0-15 sec | 1.080 mol/L | Geometric Coefficient of Variation 216.073 |
Secondary
CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B)
CC was performed following the administration of GSK2339345 or placebo at Visits 4 and 5. Capsaicin was administered using a dosimeter through a nebulizer. The number of coughs in the first and second 15 sec following each dose of CC agent were recorded. Inhalation of increased conc. was continued until the maximum dose was tolerated by the participant or the highest available conc. was used. CC agent dose concentration required to achieve C2 (2 coughs were first observed \[FO\]), C5 (5 coughs were FO) and C6 (6 coughs were FO) are presented. All instances of missing values occurred where a participant did not achieved the required number of coughs for a parameter.
Time frame: After the administration of GSK2339345 or placebo at Visits 4 and 5 in Part B (up to 2 weeks)
Population: CC population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the CC Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C2, 0-15 sec, n=10, 11 | 4.181 µmol/L | Geometric Coefficient of Variation 88.924 |
| Placebo | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C2, 0-30 sec, n=10, 11 | 4.181 µmol/L | Geometric Coefficient of Variation 88.924 |
| Placebo | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C5, 0-15 sec, n=10, 11 | 8.967 µmol/L | Geometric Coefficient of Variation 124.989 |
| Placebo | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C5, 0-30 sec, n=10, 11 | 8.367 µmol/L | Geometric Coefficient of Variation 110.36 |
| Placebo | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C6, 0-15 sec, n=10, 9 | 11.834 µmol/L | Geometric Coefficient of Variation 229.845 |
| Placebo | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C6, 0-30 sec, n=10, 10 | 10.300 µmol/L | Geometric Coefficient of Variation 229.859 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C6, 0-15 sec, n=10, 9 | 12.391 µmol/L | Geometric Coefficient of Variation 438.063 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C2, 0-15 sec, n=10, 11 | 5.697 µmol/L | Geometric Coefficient of Variation 207.575 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C5, 0-30 sec, n=10, 11 | 10.050 µmol/L | Geometric Coefficient of Variation 535.013 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C2, 0-30 sec, n=10, 11 | 5.022 µmol/L | Geometric Coefficient of Variation 194.425 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C6, 0-30 sec, n=10, 10 | 14.575 µmol/L | Geometric Coefficient of Variation 908.133 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C5, 0-15 sec, n=10, 11 | 11.394 µmol/L | Geometric Coefficient of Variation 378.087 |
Secondary
CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B)
CC was performed following the administration of GSK2339345 or placebo at Visits 4 and 5. Capsaicin was administered using a dosimeter through a nebulizer. The number of coughs in the first and second 15 sec following each dose of CC agent were recorded. Inhalation of increased Conc. was continued until the maximum dose was tolerated by the participant or the highest available Conc. was used. CC agent imputed dose concentration required to achieve C2 (at which 2 coughs were first observed \[FO\]), C5 (at which 5 coughs were FO) and C6 (at which 6 coughs were FO) are presented. For participants who did not complete the challenge and not reached the endpoint, values were imputed to the next dose in the challenge sequence after stopping. For participants who completed the challenge and had not reached the endpoint, values were imputed to 2000 (=twice the highest dose of capsaicin).
Time frame: After the administration of GSK2339345 or placebo at Visits 4 and 5 in Part B (up to 2 weeks)
Population: CC Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C2, 0-15 sec | 4.181 µmol/L | Geometric Coefficient of Variation 88.924 |
| Placebo | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C2, 0-30 sec | 4.181 µmol/L | Geometric Coefficient of Variation 88.924 |
| Placebo | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C5, 0-15 sec | 8.967 µmol/L | Geometric Coefficient of Variation 124.989 |
| Placebo | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C5, 0-30 sec | 8.367 µmol/L | Geometric Coefficient of Variation 110.36 |
| Placebo | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C6, 0-15 sec | 11.834 µmol/L | Geometric Coefficient of Variation 229.845 |
| Placebo | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C6, 0-30 sec | 10.300 µmol/L | Geometric Coefficient of Variation 229.859 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C6, 0-15 sec | 25.850 µmol/L | Geometric Coefficient of Variation 1279.694 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C2, 0-15 sec | 5.697 µmol/L | Geometric Coefficient of Variation 207.575 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C5, 0-30 sec | 10.050 µmol/L | Geometric Coefficient of Variation 535.013 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C2, 0-30 sec | 5.022 µmol/L | Geometric Coefficient of Variation 194.425 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C6, 0-30 sec | 20.100 µmol/L | Geometric Coefficient of Variation 1288.571 |
| GSK2339345 1000 Microgram (mcg) | CC Agent Imputed Dose Concentration Required to Achieve C2, C5 and C6 at Visits 4 and 5 (Part B) | C5, 0-15 sec | 11.394 µmol/L | Geometric Coefficient of Variation 378.087 |
Secondary
Maximum Observed Concentration (Cmax) of GSK2339345 Following Two Repeated Doses
Cmax is defined as the maximum observed concentration of GSK2339345 following two repeated doses at each visit in Part A. Samples were collected at the following time points: pre-dose; 2 min, 5 min, 10 min, 30 min, 1 hr and 2hr (only after Dose 1) post every dose administration at Visits 1, 2 and 3. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. For Cmax, NCs were imputed prior to derivation of summary statistics and NCs were imputed with 0.5\*LLQ (LLQ=0.20 ng/mL).
Time frame: From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks)
Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different time points, so the overall number of participants analyzed reflects everyone in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) of GSK2339345 Following Two Repeated Doses | FA, Dose 1, n=14 | 0.9485 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 224.0451 |
| Placebo | Maximum Observed Concentration (Cmax) of GSK2339345 Following Two Repeated Doses | FA, Dose 2, n=14 | 1.9212 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 138.2018 |
| Placebo | Maximum Observed Concentration (Cmax) of GSK2339345 Following Two Repeated Doses | SA, Dose 1, n=7 | 1.0835 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 474.4072 |
| Placebo | Maximum Observed Concentration (Cmax) of GSK2339345 Following Two Repeated Doses | SA, Dose 2, n=7 | 1.0448 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 416.3398 |
Secondary
Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of ALP, ALT, AST and GGT at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALP, FA, Pre-dose, n=16, 14 | 67.9 International Units/Liter (IU/L) | Standard Deviation 19.33 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALP, FA, 1 hr Post-dose, n=14, 14 | 63.7 International Units/Liter (IU/L) | Standard Deviation 16.7 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALP, SA, Pre-dose, n=6, 7 | 69.7 International Units/Liter (IU/L) | Standard Deviation 15.11 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALP, SA, 1 hr Post-dose, n=7, 7 | 69.0 International Units/Liter (IU/L) | Standard Deviation 17.45 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALT, FA, Pre-dose, n=16, 14 | 15.8 International Units/Liter (IU/L) | Standard Deviation 5.36 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALT, FA, 1 hr Post-dose, n=14, 14 | 15.2 International Units/Liter (IU/L) | Standard Deviation 5.83 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALT, SA, Pre-dose, n=6, 7 | 16.5 International Units/Liter (IU/L) | Standard Deviation 2.07 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALT, SA, 1 hr Post-dose, n=7, 7 | 15.3 International Units/Liter (IU/L) | Standard Deviation 2.75 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | AST, FA, Pre-dose, n=16, 14 | 23.1 International Units/Liter (IU/L) | Standard Deviation 10.37 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | AST, FA, 1 hr Post-dose, n=14, 13 | 21.4 International Units/Liter (IU/L) | Standard Deviation 9.87 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | AST, SA, Pre-dose, n=6, 7 | 18.5 International Units/Liter (IU/L) | Standard Deviation 4.28 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | AST, SA, 1 hr Post-dose, n=6, 7 | 16.5 International Units/Liter (IU/L) | Standard Deviation 3.51 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | GGT, FA, Pre-dose, n=16, 14 | 24.6 International Units/Liter (IU/L) | Standard Deviation 12.93 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | GGT, FA, 1 hr Post-dose, n=14, 14 | 24.6 International Units/Liter (IU/L) | Standard Deviation 13.89 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | GGT, SA, Pre-dose, n=6, 7 | 20.7 International Units/Liter (IU/L) | Standard Deviation 9.18 |
| Placebo | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | GGT, SA, 1 hr Post-dose, n=7, 7 | 25.0 International Units/Liter (IU/L) | Standard Deviation 15.58 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | GGT, SA, 1 hr Post-dose, n=7, 7 | 22.0 International Units/Liter (IU/L) | Standard Deviation 13.17 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALP, FA, Pre-dose, n=16, 14 | 64.1 International Units/Liter (IU/L) | Standard Deviation 15.01 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | AST, FA, Pre-dose, n=16, 14 | 19.6 International Units/Liter (IU/L) | Standard Deviation 3.98 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALP, FA, 1 hr Post-dose, n=14, 14 | 60.6 International Units/Liter (IU/L) | Standard Deviation 13.67 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | GGT, FA, Pre-dose, n=16, 14 | 22.8 International Units/Liter (IU/L) | Standard Deviation 9.95 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALP, SA, Pre-dose, n=6, 7 | 57.4 International Units/Liter (IU/L) | Standard Deviation 13.36 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | AST, FA, 1 hr Post-dose, n=14, 13 | 20.7 International Units/Liter (IU/L) | Standard Deviation 7.51 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALP, SA, 1 hr Post-dose, n=7, 7 | 55.9 International Units/Liter (IU/L) | Standard Deviation 13.59 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | GGT, SA, Pre-dose, n=6, 7 | 22.9 International Units/Liter (IU/L) | Standard Deviation 12.82 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALT, FA, Pre-dose, n=16, 14 | 13.9 International Units/Liter (IU/L) | Standard Deviation 4.62 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | AST, SA, Pre-dose, n=6, 7 | 21.6 International Units/Liter (IU/L) | Standard Deviation 6.45 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALT, FA, 1 hr Post-dose, n=14, 14 | 14.1 International Units/Liter (IU/L) | Standard Deviation 5.77 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | GGT, FA, 1 hr Post-dose, n=14, 14 | 22.4 International Units/Liter (IU/L) | Standard Deviation 9.85 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALT, SA, Pre-dose, n=6, 7 | 13.6 International Units/Liter (IU/L) | Standard Deviation 5.74 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | AST, SA, 1 hr Post-dose, n=6, 7 | 19.7 International Units/Liter (IU/L) | Standard Deviation 7.11 |
| GSK2339345 1000 Microgram (mcg) | Mean Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma Glutamyl Transferase (GGT) Values at the Indicated Time Points in Part A | ALT, SA, 1 hr Post-dose, n=7, 7 | 12.9 International Units/Liter (IU/L) | Standard Deviation 6.54 |
Secondary
Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC - absolute neutrophil count), platelet count, and white blood cells count at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All subject population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Monocytes, SA, Pre-dose, n=6, 7 | 0.390 10^9 cells/Liter (GI/L) | Standard Deviation 0.1517 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Eosinophils, FA, Pre-dose, n=16, 14 | 0.091 10^9 cells/Liter (GI/L) | Standard Deviation 0.0604 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Monocytes, SA, 1 hr Post-dose, n=7, 7 | 0.380 10^9 cells/Liter (GI/L) | Standard Deviation 0.1319 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Lymphocytes, FA, Pre-dose, n=16, 14 | 1.801 10^9 cells/Liter (GI/L) | Standard Deviation 0.4214 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Total Neutrophils, FA, Pre-dose, n=16, 14 | 4.256 10^9 cells/Liter (GI/L) | Standard Deviation 1.3244 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Basophils, FA, 1 hr Post-dose, n=14, 13 | 0.031 10^9 cells/Liter (GI/L) | Standard Deviation 0.0192 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Total Neutrophils, FA, 1 hr Post-dose, n=14, 13 | 4.730 10^9 cells/Liter (GI/L) | Standard Deviation 1.3512 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Lymphocytes, FA, 1 hr Post-dose, n=14, 13 | 2.095 10^9 cells/Liter (GI/L) | Standard Deviation 0.4572 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Total Neutrophils, SA, Pre-dose, n=6, 7 | 4.238 10^9 cells/Liter (GI/L) | Standard Deviation 1.4993 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Eosinophils, FA, 1 hr Post-dose, n=14, 13 | 0.106 10^9 cells/Liter (GI/L) | Standard Deviation 0.0776 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Total Neutrophils, SA, 1 hr Post-dose, n=7, 7 | 4.847 10^9 cells/Liter (GI/L) | Standard Deviation 1.4473 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Lymphocytes, SA, Pre-dose, n=6, 7 | 1.922 10^9 cells/Liter (GI/L) | Standard Deviation 0.4492 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Platelet count, FA, Pre-dose, n=16, 13 | 225.8 10^9 cells/Liter (GI/L) | Standard Deviation 51.14 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Basophils, SA, 1 hr Post-dose, n=7, 7 | 0.019 10^9 cells/Liter (GI/L) | Standard Deviation 0.0107 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Platelet count, FA, 1 hr Post-dose, n=14, 13 | 209.1 10^9 cells/Liter (GI/L) | Standard Deviation 49.01 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Lymphocytes, SA, 1 hr Post-dose, n=7, 7 | 2.200 10^9 cells/Liter (GI/L) | Standard Deviation 0.6387 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Platelet count, SA, Pre-dose, n=6, 7 | 259.8 10^9 cells/Liter (GI/L) | Standard Deviation 36.98 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Eosinophils, SA, Pre-dose, n=6, 7 | 0.080 10^9 cells/Liter (GI/L) | Standard Deviation 0.051 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Platelet count, SA, 1 hr Post-dose, n=7, 7 | 238.4 10^9 cells/Liter (GI/L) | Standard Deviation 53.37 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Monocytes, FA, Pre-dose, n=16, 14 | 0.363 10^9 cells/Liter (GI/L) | Standard Deviation 0.1373 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | WBC count, FA, Pre-dose, n=16, 14 | 6.54 10^9 cells/Liter (GI/L) | Standard Deviation 1.565 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Basophils, SA, Pre-dose, n=6, 7 | 0.040 10^9 cells/Liter (GI/L) | Standard Deviation 0.0329 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | WBC count, FA, 1 hr Post-dose, n=14, 13 | 7.36 10^9 cells/Liter (GI/L) | Standard Deviation 1.663 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Monocytes, FA, 1 hr Post-dose, n=14, 13 | 0.414 10^9 cells/Liter (GI/L) | Standard Deviation 0.1249 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | WBC count, SA, Pre-dose, n=6, 7 | 6.67 10^9 cells/Liter (GI/L) | Standard Deviation 1.56 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Eosinophils, SA, 1 hr Post-dose, n=7, 7 | 0.113 10^9 cells/Liter (GI/L) | Standard Deviation 0.0502 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | WBC count, SA, 1 hr Post-dose, n=7, 7 | 7.53 10^9 cells/Liter (GI/L) | Standard Deviation 1.798 |
| Placebo | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Basophils, FA, Pre-dose, n=16, 14 | 0.026 10^9 cells/Liter (GI/L) | Standard Deviation 0.0126 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | WBC count, SA, 1 hr Post-dose, n=7, 7 | 6.66 10^9 cells/Liter (GI/L) | Standard Deviation 0.81 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Basophils, FA, Pre-dose, n=16, 14 | 0.023 10^9 cells/Liter (GI/L) | Standard Deviation 0.0159 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Basophils, FA, 1 hr Post-dose, n=14, 13 | 0.032 10^9 cells/Liter (GI/L) | Standard Deviation 0.0242 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Basophils, SA, Pre-dose, n=6, 7 | 0.026 10^9 cells/Liter (GI/L) | Standard Deviation 0.0162 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Basophils, SA, 1 hr Post-dose, n=7, 7 | 0.036 10^9 cells/Liter (GI/L) | Standard Deviation 0.0299 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Eosinophils, FA, Pre-dose, n=16, 14 | 0.063 10^9 cells/Liter (GI/L) | Standard Deviation 0.0365 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Eosinophils, FA, 1 hr Post-dose, n=14, 13 | 0.093 10^9 cells/Liter (GI/L) | Standard Deviation 0.0471 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Eosinophils, SA, Pre-dose, n=6, 7 | 0.064 10^9 cells/Liter (GI/L) | Standard Deviation 0.0299 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Eosinophils, SA, 1 hr Post-dose, n=7, 7 | 0.080 10^9 cells/Liter (GI/L) | Standard Deviation 0.0191 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Lymphocytes, FA, Pre-dose, n=16, 14 | 1.673 10^9 cells/Liter (GI/L) | Standard Deviation 0.3348 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Lymphocytes, FA, 1 hr Post-dose, n=14, 13 | 1.977 10^9 cells/Liter (GI/L) | Standard Deviation 0.5392 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Lymphocytes, SA, Pre-dose, n=6, 7 | 1.536 10^9 cells/Liter (GI/L) | Standard Deviation 0.3406 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Lymphocytes, SA, 1 hr Post-dose, n=7, 7 | 1.926 10^9 cells/Liter (GI/L) | Standard Deviation 0.2486 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Monocytes, FA, Pre-dose, n=16, 14 | 0.369 10^9 cells/Liter (GI/L) | Standard Deviation 0.1957 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Monocytes, FA, 1 hr Post-dose, n=14, 13 | 0.434 10^9 cells/Liter (GI/L) | Standard Deviation 0.1601 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Monocytes, SA, Pre-dose, n=6, 7 | 0.297 10^9 cells/Liter (GI/L) | Standard Deviation 0.0525 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Monocytes, SA, 1 hr Post-dose, n=7, 7 | 0.364 10^9 cells/Liter (GI/L) | Standard Deviation 0.0479 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Total Neutrophils, FA, Pre-dose, n=16, 14 | 4.206 10^9 cells/Liter (GI/L) | Standard Deviation 1.123 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Total Neutrophils, FA, 1 hr Post-dose, n=14, 13 | 4.800 10^9 cells/Liter (GI/L) | Standard Deviation 1.1399 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Total Neutrophils, SA, Pre-dose, n=6, 7 | 3.993 10^9 cells/Liter (GI/L) | Standard Deviation 0.9757 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Total Neutrophils, SA, 1 hr Post-dose, n=7, 7 | 4.250 10^9 cells/Liter (GI/L) | Standard Deviation 0.6064 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Platelet count, FA, Pre-dose, n=16, 13 | 233.4 10^9 cells/Liter (GI/L) | Standard Deviation 56.53 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Platelet count, FA, 1 hr Post-dose, n=14, 13 | 215.7 10^9 cells/Liter (GI/L) | Standard Deviation 30.69 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Platelet count, SA, Pre-dose, n=6, 7 | 238.6 10^9 cells/Liter (GI/L) | Standard Deviation 47.9 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | Platelet count, SA, 1 hr Post-dose, n=7, 7 | 232.3 10^9 cells/Liter (GI/L) | Standard Deviation 49.45 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | WBC count, FA, Pre-dose, n=16, 14 | 6.33 10^9 cells/Liter (GI/L) | Standard Deviation 1.315 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | WBC count, FA, 1 hr Post-dose, n=14, 13 | 7.33 10^9 cells/Liter (GI/L) | Standard Deviation 1.596 |
| GSK2339345 1000 Microgram (mcg) | Mean Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, and White Blood Cells (WBC) Count Values at the Indicated Time Points in Part A | WBC count, SA, Pre-dose, n=6, 7 | 5.91 10^9 cells/Liter (GI/L) | Standard Deviation 1.263 |
Secondary
Mean Body Temperature at the Indicated Time Points in Parts A, B and C
Body temperature measurements were obtained at1 hr post-dose 2 FA and SA in Part A and each administration in Parts B, and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: 1 hr post the second dose administered in Part A and 1 hr post each dose administered in Parts B and C (up to 8 Weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Body Temperature at the Indicated Time Points in Parts A, B and C | Part B, 1 hr, n=10, 10 | 36.55 Degree Celsius | Standard Deviation 0.536 |
| Placebo | Mean Body Temperature at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 1 hr, n=15, 12 | 36.84 Degree Celsius | Standard Deviation 0.47 |
| Placebo | Mean Body Temperature at the Indicated Time Points in Parts A, B and C | Part C, 1 hr, n=9, 9 | 36.54 Degree Celsius | Standard Deviation 0.391 |
| Placebo | Mean Body Temperature at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 1 hr, n=7, 7 | 36.56 Degree Celsius | Standard Deviation 0.541 |
| GSK2339345 1000 Microgram (mcg) | Mean Body Temperature at the Indicated Time Points in Parts A, B and C | Part C, 1 hr, n=9, 9 | 36.69 Degree Celsius | Standard Deviation 0.473 |
| GSK2339345 1000 Microgram (mcg) | Mean Body Temperature at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 1 hr, n=15, 12 | 36.70 Degree Celsius | Standard Deviation 0.484 |
| GSK2339345 1000 Microgram (mcg) | Mean Body Temperature at the Indicated Time Points in Parts A, B and C | Part B, 1 hr, n=10, 10 | 36.76 Degree Celsius | Standard Deviation 0.414 |
| GSK2339345 1000 Microgram (mcg) | Mean Body Temperature at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 1 hr, n=7, 7 | 36.80 Degree Celsius | Standard Deviation 0.52 |
Secondary
Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of calcium, chloride, glucose, potassium, sodium, and urea/blood urea nitrogen (BUN) at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Chloride, SA, Pre-dose, n=6, 7 | 103.6 Millimoles per liter (mmol/L) | Standard Deviation 3.02 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Calcium, FA, 1 hr Post-dose, n=14, 13 | 2.34 Millimoles per liter (mmol/L) | Standard Deviation 0.099 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Calcium, SA, Pre-dose, n=6, 7 | 2.41 Millimoles per liter (mmol/L) | Standard Deviation 0.102 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Calcium, SA, 1 hr Post-dose, n=6, 7 | 2.34 Millimoles per liter (mmol/L) | Standard Deviation 0.061 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Chloride, FA, Pre-dose, n=16, 14 | 103.6 Millimoles per liter (mmol/L) | Standard Deviation 2.31 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Chloride, FA, 1 hr Post-dose, n=14, 14 | 103.6 Millimoles per liter (mmol/L) | Standard Deviation 2.06 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Calcium, FA, Pre-dose, n=16, 14 | 2.37 Millimoles per liter (mmol/L) | Standard Deviation 0.085 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Chloride, SA, 1 hr Post-dose, n=7, 7 | 104.9 Millimoles per liter (mmol/L) | Standard Deviation 4.26 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Glucose, FA, Pre-dose, n=16, 14 | 5.28 Millimoles per liter (mmol/L) | Standard Deviation 0.884 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Glucose, FA, 1 hr Post-dose, n=14, 14 | 5.59 Millimoles per liter (mmol/L) | Standard Deviation 1.124 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Glucose, SA, Pre-dose, n=6, 7 | 5.03 Millimoles per liter (mmol/L) | Standard Deviation 1.108 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Glucose, SA, 1 hr Post-dose, n=7, 7 | 5.46 Millimoles per liter (mmol/L) | Standard Deviation 1.165 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Potassium, FA, Pre-dose, n=16, 14 | 4.18 Millimoles per liter (mmol/L) | Standard Deviation 0.246 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Potassium, FA, 1 hr Post-dose, n=14, 13 | 3.94 Millimoles per liter (mmol/L) | Standard Deviation 0.318 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Potassium, SA, Pre-dose, n=6, 7 | 4.22 Millimoles per liter (mmol/L) | Standard Deviation 0.24 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Potassium, SA, 1 hr Post-dose, n=6, 7 | 4.12 Millimoles per liter (mmol/L) | Standard Deviation 0.736 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Sodium, FA, Pre-dose, n=16, 14 | 138.6 Millimoles per liter (mmol/L) | Standard Deviation 1.59 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Sodium, FA, 1 hr Post-dose, n=14, 14 | 138.8 Millimoles per liter (mmol/L) | Standard Deviation 1.93 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Sodium, SA, Pre-dose, n=6, 7 | 139.0 Millimoles per liter (mmol/L) | Standard Deviation 1.26 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Sodium, SA, 1 hr Post-dose, n=7, 7 | 140.0 Millimoles per liter (mmol/L) | Standard Deviation 4.58 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Urea/BUN, FA, Pre-dose, n=16, 14 | 4.91 Millimoles per liter (mmol/L) | Standard Deviation 1.909 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Urea/BUN, FA, 1 hr Post-dose, n=14, 14 | 5.04 Millimoles per liter (mmol/L) | Standard Deviation 2.008 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Urea/BUN, SA, Pre-dose, n=6, 7 | 4.03 Millimoles per liter (mmol/L) | Standard Deviation 1.791 |
| Placebo | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Urea/BUN, SA, 1 hr Post-dose, n=7, 7 | 5.00 Millimoles per liter (mmol/L) | Standard Deviation 2.309 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Urea/BUN, SA, Pre-dose, n=6, 7 | 4.81 Millimoles per liter (mmol/L) | Standard Deviation 1.732 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Calcium, FA, Pre-dose, n=16, 14 | 2.39 Millimoles per liter (mmol/L) | Standard Deviation 0.107 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Potassium, FA, Pre-dose, n=16, 14 | 4.18 Millimoles per liter (mmol/L) | Standard Deviation 0.229 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Calcium, FA, 1 hr Post-dose, n=14, 13 | 2.34 Millimoles per liter (mmol/L) | Standard Deviation 0.091 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Sodium, SA, Pre-dose, n=6, 7 | 138.4 Millimoles per liter (mmol/L) | Standard Deviation 0.98 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Calcium, SA, Pre-dose, n=6, 7 | 2.37 Millimoles per liter (mmol/L) | Standard Deviation 0.095 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Potassium, FA, 1 hr Post-dose, n=14, 13 | 4.55 Millimoles per liter (mmol/L) | Standard Deviation 1.028 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Calcium, SA, 1 hr Post-dose, n=6, 7 | 2.32 Millimoles per liter (mmol/L) | Standard Deviation 0.11 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Urea/BUN, FA, 1 hr Post-dose, n=14, 14 | 5.21 Millimoles per liter (mmol/L) | Standard Deviation 2.104 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Chloride, FA, Pre-dose, n=16, 14 | 103.4 Millimoles per liter (mmol/L) | Standard Deviation 2.13 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Potassium, SA, Pre-dose, n=6, 7 | 4.11 Millimoles per liter (mmol/L) | Standard Deviation 0.241 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Chloride, FA, 1 hr Post-dose, n=14, 14 | 104.3 Millimoles per liter (mmol/L) | Standard Deviation 2.2 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Sodium, SA, 1 hr Post-dose, n=7, 7 | 138.7 Millimoles per liter (mmol/L) | Standard Deviation 1.6 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Chloride, SA, Pre-dose, n=6, 7 | 103.0 Millimoles per liter (mmol/L) | Standard Deviation 1.73 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Potassium, SA, 1 hr Post-dose, n=6, 7 | 3.93 Millimoles per liter (mmol/L) | Standard Deviation 0.206 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Chloride, SA, 1 hr Post-dose, n=7, 7 | 103.6 Millimoles per liter (mmol/L) | Standard Deviation 1.4 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Urea/BUN, SA, 1 hr Post-dose, n=7, 7 | 5.24 Millimoles per liter (mmol/L) | Standard Deviation 1.706 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Glucose, FA, Pre-dose, n=16, 14 | 5.19 Millimoles per liter (mmol/L) | Standard Deviation 0.791 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Sodium, FA, Pre-dose, n=16, 14 | 138.9 Millimoles per liter (mmol/L) | Standard Deviation 1.51 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Glucose, FA, 1 hr Post-dose, n=14, 14 | 5.69 Millimoles per liter (mmol/L) | Standard Deviation 1.279 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Urea/BUN, FA, Pre-dose, n=16, 14 | 4.86 Millimoles per liter (mmol/L) | Standard Deviation 1.934 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Glucose, SA, Pre-dose, n=6, 7 | 5.06 Millimoles per liter (mmol/L) | Standard Deviation 0.629 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Sodium, FA, 1 hr Post-dose, n=14, 14 | 138.1 Millimoles per liter (mmol/L) | Standard Deviation 1.99 |
| GSK2339345 1000 Microgram (mcg) | Mean Calcium, Chloride, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) Values at the Indicated Time Points in Part A | Glucose, SA, 1 hr Post-dose, n=7, 7 | 5.24 Millimoles per liter (mmol/L) | Standard Deviation 0.873 |
Secondary
Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of mean corpuscle hemoglobin at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All subject population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 29.87 picograms per cell (pg) | Standard Deviation 1.709 |
| Placebo | Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=14, 13 | 29.75 picograms per cell (pg) | Standard Deviation 1.874 |
| Placebo | Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | SA, Pre-dose, n=6, 7 | 29.48 picograms per cell (pg) | Standard Deviation 1.958 |
| Placebo | Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 29.67 picograms per cell (pg) | Standard Deviation 1.864 |
| GSK2339345 1000 Microgram (mcg) | Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 29.40 picograms per cell (pg) | Standard Deviation 1.672 |
| GSK2339345 1000 Microgram (mcg) | Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 29.75 picograms per cell (pg) | Standard Deviation 1.787 |
| GSK2339345 1000 Microgram (mcg) | Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | SA, Pre-dose, n=6, 7 | 29.67 picograms per cell (pg) | Standard Deviation 1.627 |
| GSK2339345 1000 Microgram (mcg) | Mean Corpuscle Hemoglobin Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=14, 13 | 29.85 picograms per cell (pg) | Standard Deviation 1.859 |
Secondary
Mean Corpuscle Volume Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of mean corpuscle volume at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Corpuscle Volume Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 91.8 femtoliters per cell (fL) | Standard Deviation 5.03 |
| Placebo | Mean Corpuscle Volume Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=14, 13 | 91.0 femtoliters per cell (fL) | Standard Deviation 5.04 |
| Placebo | Mean Corpuscle Volume Values at the Indicated Time Points in Part A | SA, Pre-dose, n=6, 7 | 90.0 femtoliters per cell (fL) | Standard Deviation 6.19 |
| Placebo | Mean Corpuscle Volume Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 90.4 femtoliters per cell (fL) | Standard Deviation 5.72 |
| GSK2339345 1000 Microgram (mcg) | Mean Corpuscle Volume Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 91.2 femtoliters per cell (fL) | Standard Deviation 5.66 |
| GSK2339345 1000 Microgram (mcg) | Mean Corpuscle Volume Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 91.3 femtoliters per cell (fL) | Standard Deviation 5.21 |
| GSK2339345 1000 Microgram (mcg) | Mean Corpuscle Volume Values at the Indicated Time Points in Part A | SA, Pre-dose, n=6, 7 | 91.6 femtoliters per cell (fL) | Standard Deviation 5.49 |
| GSK2339345 1000 Microgram (mcg) | Mean Corpuscle Volume Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=14, 13 | 90.8 femtoliters per cell (fL) | Standard Deviation 5.63 |
Secondary
Mean Cough Count Over 4 Hours at Visits 1, 2 and 3 (Part A)
Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3 (4- hrs of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. The cough count over 4-hrs was done by using the sum of first 4-hrs starting from the time of first dose and the second 4-hrs starting at the time of the second dose respectively. Number of coughs in 0-4 hr and 4-8 hr period was log-e transformed and used for the analysis. Values were imputed pro-rata if 4 hr epoch was less than 4 hr. Mean of the total cough counts over 4-hrs recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported.
Time frame: Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A)
Population: All Subjects Population. Only participants with at least one 4 hr cough count were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Cough Count Over 4 Hours at Visits 1, 2 and 3 (Part A) | 4-8 hr | 65.1 Cough count | Standard Error 0.234 |
| Placebo | Mean Cough Count Over 4 Hours at Visits 1, 2 and 3 (Part A) | 0-4 hr | 70.5 Cough count | Standard Error 0.257 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Count Over 4 Hours at Visits 1, 2 and 3 (Part A) | 0-4 hr | 86.7 Cough count | Standard Error 0.257 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Count Over 4 Hours at Visits 1, 2 and 3 (Part A) | 4-8 hr | 88.4 Cough count | Standard Error 0.234 |
90% CI: [0.86, 1.75]
90% CI: [1.07, 1.72]
Secondary
Mean Cough Counts by 15 Min Epoch in Part A
Cough counts (8 hr of recording) were conducted at Visits 1, 2 and 3 (4-hr of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participant for 8 hr post Dose 1. The first epoch started at the time of the first dose, and the 15 min time periods continued until an epoch ended immediately before the second dose (or 4h after the first dose if earlier). The epochs were then re-started at the start of the second dose at 15 min intervals, finishing with an epoch which ran to 4-hr after the start of the second dose. The cough counts were sum-up by the treatments received by the participants. Mean cough count was calculated per participant if the same treatment was taken during different periods.
Time frame: Up to 8 hours post-dose at Visits 1, 2 and 3 in Part A (up to 3 weeks)
Population: All Subjects Population. Only those participants with a 15 min cough count value were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 2 to 2.25 hr | 4.0 Cough count | Standard Deviation 7.26 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 0.25 to 0.5 hr | 10.7 Cough count | Standard Deviation 14.99 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 0.5 to 0.75 hr | 22.5 Cough count | Standard Deviation 21.1 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 0.75 to 1 hr | 3.7 Cough count | Standard Deviation 6.11 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 1 to 1.25 hr | 4.9 Cough count | Standard Deviation 7.53 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 1.25 to 1.5 hr | 2.3 Cough count | Standard Deviation 4.13 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 1.5 to 1.75 hr | 3.5 Cough count | Standard Deviation 3.08 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 1.75 to 2 hr | 3.3 Cough count | Standard Deviation 2.96 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 0 to 0.25 hr | 4.6 Cough count | Standard Deviation 7.84 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 2.25 to 2.5 hr | 1.9 Cough count | Standard Deviation 3.04 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 2.5 to 2.75 hr | 0.4 Cough count | Standard Deviation 0.94 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 2.75 to 3 hr | 4.6 Cough count | Standard Deviation 7.26 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 3 to 3.25 hr | 8.4 Cough count | Standard Deviation 14.45 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 3.25 to 3.5 hr | 10.9 Cough count | Standard Deviation 13.44 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 3.5 to 3.75 hr | 7.7 Cough count | Standard Deviation 11.21 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 3.75 to 4 hr | 11.5 Cough count | Standard Deviation 20.13 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 4 to 4.25 hr | 1.6 Cough count | Standard Deviation 2.88 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 4.25 to 4.5 hr | 3.8 Cough count | Standard Deviation 5.97 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 4.5 to 4.75 hr | 12.4 Cough count | Standard Deviation 13.16 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 4.75 to 5 hr | 2.6 Cough count | Standard Deviation 4.79 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 5 to 5.25 hr | 9.6 Cough count | Standard Deviation 17.34 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 5.25 to 5.5 hr | 9.5 Cough count | Standard Deviation 16.54 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 5.5 to 5.75 hr | 2.1 Cough count | Standard Deviation 3.35 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 5.75 to 6 hr | 4.1 Cough count | Standard Deviation 8.91 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 6 to 6.25 hr | 6.8 Cough count | Standard Deviation 13.83 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 6.25 to 6.5 hr | 5.2 Cough count | Standard Deviation 6.6 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 6.5 to 6.75 hr | 7.2 Cough count | Standard Deviation 14.53 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 6.75 to 7 hr | 9.5 Cough count | Standard Deviation 16.17 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 7 to 7.25 hr | 6.9 Cough count | Standard Deviation 7.63 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 7.25 to 7.5 hr | 9.6 Cough count | Standard Deviation 15.81 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 7.5 to 7.75 hr | 6.9 Cough count | Standard Deviation 18.06 |
| Placebo | Mean Cough Counts by 15 Min Epoch in Part A | 7.75 to 8 hr | 9.1 Cough count | Standard Deviation 19.35 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 7.75 to 8 hr | 11.7 Cough count | Standard Deviation 33.1 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 0 to 0.25 hr | 21.1 Cough count | Standard Deviation 18.23 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 4 to 4.25 hr | 23.0 Cough count | Standard Deviation 17.97 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 0.25 to 0.5 hr | 4.6 Cough count | Standard Deviation 9.21 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 6 to 6.25 hr | 3.2 Cough count | Standard Deviation 4.39 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 0.5 to 0.75 hr | 18.7 Cough count | Standard Deviation 19.54 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 4.25 to 4.5 hr | 12.5 Cough count | Standard Deviation 28.66 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 0.75 to 1 hr | 2.4 Cough count | Standard Deviation 3.91 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 7 to 7.25 hr | 7.1 Cough count | Standard Deviation 11.2 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 1 to 1.25 hr | 5.7 Cough count | Standard Deviation 6.91 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 4.5 to 4.75 hr | 15.6 Cough count | Standard Deviation 19.11 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 1.25 to 1.5 hr | 3.5 Cough count | Standard Deviation 4.19 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 6.25 to 6.5 hr | 4.3 Cough count | Standard Deviation 6.01 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 1.5 to 1.75 hr | 3.4 Cough count | Standard Deviation 3.67 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 4.75 to 5 hr | 3.5 Cough count | Standard Deviation 5.51 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 1.75 to 2 hr | 3.1 Cough count | Standard Deviation 3.61 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 7.5 to 7.75 hr | 4.9 Cough count | Standard Deviation 6.24 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 2 to 2.25 hr | 6.9 Cough count | Standard Deviation 9.04 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 5 to 5.25 hr | 12.0 Cough count | Standard Deviation 28.61 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 2.25 to 2.5 hr | 3.5 Cough count | Standard Deviation 4.77 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 6.5 to 6.75 hr | 2.8 Cough count | Standard Deviation 4.67 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 2.5 to 2.75 hr | 1.5 Cough count | Standard Deviation 4.39 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 5.25 to 5.5 hr | 9.1 Cough count | Standard Deviation 21.65 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 2.75 to 3 hr | 5.1 Cough count | Standard Deviation 6.34 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 7.25 to 7.5 hr | 4.3 Cough count | Standard Deviation 5.51 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 3 to 3.25 hr | 8.8 Cough count | Standard Deviation 13.61 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 5.5 to 5.75 hr | 3.9 Cough count | Standard Deviation 6.34 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 3.25 to 3.5 hr | 7.7 Cough count | Standard Deviation 11.34 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 6.75 to 7 hr | 8.5 Cough count | Standard Deviation 12.8 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 3.5 to 3.75 hr | 5.5 Cough count | Standard Deviation 8.6 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 5.75 to 6 hr | 3.9 Cough count | Standard Deviation 6.24 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 15 Min Epoch in Part A | 3.75 to 4 hr | 14.6 Cough count | Standard Deviation 21.35 |
Secondary
Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A)
Cough counts (8 hr of recording) were conducted at Visits 1, 2 and 3 (4-hr of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participant for 8 hr post Dose 1. The first epoch started at the time of the first dose, and the 60 min time periods continued until an epoch ended immediately before the second dose (or 4-hr after the first dose if earlier). The epochs were then re-started at the start of the second dose at 60 min intervals, finishing with an epoch which ran to 4-hrs after the start of the second dose. The cough counts were sum-up by the treatments received by the participants. Mean cough count was calculated per participant if the same treatment was taken during different periods. Values were imputed pro-rata if 1 hr epoch is less than 60 min.
Time frame: Up to 8 hours post-dose at Visits 1, 2 and 3 in Part A (up to 3 weeks)
Population: All Subjects Population. Only those participants with a 1 hr cough count value were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 0 to 1 hr | 41.5 Cough count | Standard Deviation 30.25 |
| Placebo | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 1 to 2 hr | 13.9 Cough count | Standard Deviation 9.86 |
| Placebo | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 2 to 3 hr | 11.0 Cough count | Standard Deviation 11.68 |
| Placebo | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 3 to 4 hr | 38.4 Cough count | Standard Deviation 35.63 |
| Placebo | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 4 to 5 hr | 20.4 Cough count | Standard Deviation 14.78 |
| Placebo | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 5 to 6 hr | 25.3 Cough count | Standard Deviation 43.09 |
| Placebo | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 6 to 7 hr | 28.7 Cough count | Standard Deviation 44.03 |
| Placebo | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 7 to 8 hr | 32.5 Cough count | Standard Deviation 54.26 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 7 to 8 hr | 28.2 Cough count | Standard Deviation 42.78 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 0 to 1 hr | 46.8 Cough count | Standard Deviation 35.58 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 4 to 5 hr | 54.7 Cough count | Standard Deviation 61.49 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 1 to 2 hr | 15.7 Cough count | Standard Deviation 11.2 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 6 to 7 hr | 18.7 Cough count | Standard Deviation 22.79 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 2 to 3 hr | 17.0 Cough count | Standard Deviation 11.75 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 5 to 6 hr | 28.9 Cough count | Standard Deviation 51.83 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 1 hr Epoch at Visits 1, 2 and 3 (Part A) | 3 to 4 hr | 36.6 Cough count | Standard Deviation 26.4 |
Secondary
Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A)
Cough counts (8 hr of recording) were conducted at Visits 1, 2 and 3 (4-hr of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participant for 8 hr post Dose 1. The first epoch started at the time of the first dose, and the 30 min time periods continued until an epoch ended immediately before the second dose (or 4-hr after the first dose if earlier). The epochs were then re-started at the start of the second dose at 30 min intervals, finishing with an epoch which ran to 4-hr after the start of the second dose. The cough counts were sum-up by the treatments received by the participants. Mean cough count was calculated per participant if the same treatment was taken during different periods.
Time frame: Up to 8 hours post-dose in Visits 1, 2 and 3 in Part A (up to 3 weeks)
Population: All Subjects Population. Only those participants with a 30 min cough count value were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 7.5 to 8 hr | 16.0 Cough count | Standard Deviation 37.36 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 0.5 to 1 hr | 26.2 Cough count | Standard Deviation 22.58 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 1 to 1.5 hr | 7.1 Cough count | Standard Deviation 7.8 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 1.5 to 2 hr | 6.7 Cough count | Standard Deviation 4.86 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 2 to 2.5 hr | 5.9 Cough count | Standard Deviation 8.35 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 2.5 to 3 hr | 5.1 Cough count | Standard Deviation 7.41 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 3 to 3.5 hr | 19.2 Cough count | Standard Deviation 21.84 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 3.5 to 4 hr | 19.2 Cough count | Standard Deviation 28.72 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 4 to 4.5 hr | 5.4 Cough count | Standard Deviation 6.24 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 4.5 to 5 hr | 15.0 Cough count | Standard Deviation 12.17 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 5 to 5.5 hr | 19.1 Cough count | Standard Deviation 31.94 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 5.5 to 6 hr | 6.2 Cough count | Standard Deviation 11.75 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 6 to 6.5 hr | 12.0 Cough count | Standard Deviation 17.57 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 6.5 to 7 hr | 16.7 Cough count | Standard Deviation 29.71 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 7 to 7.5 hr | 16.5 Cough count | Standard Deviation 18.71 |
| Placebo | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 0 to 0.5 hr | 15.3 Cough count | Standard Deviation 17.93 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 7.5 to 8 hr | 16.6 Cough count | Standard Deviation 33.54 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 0 to 0.5 hr | 25.7 Cough count | Standard Deviation 21.17 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 4 to 4.5 hr | 35.5 Cough count | Standard Deviation 44.15 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 3 to 3.5 hr | 16.5 Cough count | Standard Deviation 15.6 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 0.5 to 1 hr | 21.1 Cough count | Standard Deviation 22.18 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 6.5 to 7 hr | 11.3 Cough count | Standard Deviation 16.92 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 1 to 1.5 hr | 9.1 Cough count | Standard Deviation 8.29 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 4.5 to 5 hr | 19.2 Cough count | Standard Deviation 21.38 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 1.5 to 2 hr | 6.6 Cough count | Standard Deviation 6.1 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 6 to 6.5 hr | 7.4 Cough count | Standard Deviation 8.26 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 2 to 2.5 hr | 10.4 Cough count | Standard Deviation 10.29 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 5 to 5.5 hr | 21.1 Cough count | Standard Deviation 49.66 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 2.5 to 3 hr | 6.6 Cough count | Standard Deviation 8.67 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 7 to 7.5 hr | 11.4 Cough count | Standard Deviation 15.1 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 5.5 to 6 hr | 7.8 Cough count | Standard Deviation 10.6 |
| GSK2339345 1000 Microgram (mcg) | Mean Cough Counts by 30 Min Epoch at Visits 1, 2 and 3 (Part A) | 3.5 to 4 hr | 20.1 Cough count | Standard Deviation 23.39 |
Secondary
Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement ofdirect bilirubin, total bilirubin, creatinine and uric acid at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Direct bilirubin, FA, Pre-dose, n=13, 11 | 1.77 Micromoles per liter (µmol/L) | Standard Deviation 0.832 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Direct bilirubin, FA, 1 hr Post-dose, n=10, 11 | 1.80 Micromoles per liter (µmol/L) | Standard Deviation 0.919 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Direct bilirubin, SA, Pre-dose, n=4, 6 | 1.75 Micromoles per liter (µmol/L) | Standard Deviation 0.957 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Direct bilirubin, SA, 1 hr Post-dose, n=5, 6 | 1.20 Micromoles per liter (µmol/L) | Standard Deviation 0.447 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Total bilirubin, FA, Pre-dose, n=16, 14 | 8.07 Micromoles per liter (µmol/L) | Standard Deviation 3.999 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Total bilirubin, FA, 1 hr Post-dose, n=14, 14 | 7.04 Micromoles per liter (µmol/L) | Standard Deviation 4.185 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Total bilirubin, SA, Pre-dose, n=6, 7 | 7.35 Micromoles per liter (µmol/L) | Standard Deviation 3.075 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Total bilirubin, SA, 1 hr Post-dose, n=7, 7 | 6.59 Micromoles per liter (µmol/L) | Standard Deviation 3.204 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Creatinine, FA, Pre-dose, n=16, 14 | 65.1 Micromoles per liter (µmol/L) | Standard Deviation 12.99 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Creatinine, FA, 1 hr Post-dose, n=14, 14 | 65.0 Micromoles per liter (µmol/L) | Standard Deviation 12.29 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Creatinine, SA, Pre-dose, n=6, 7 | 61.1 Micromoles per liter (µmol/L) | Standard Deviation 11.82 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Creatinine, SA, 1 hr Post-dose, n=7, 7 | 63.0 Micromoles per liter (µmol/L) | Standard Deviation 10.92 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Uric acid, FA, Pre-dose, n=16, 14 | 283.1 Micromoles per liter (µmol/L) | Standard Deviation 66.3 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Uric acid, FA, 1 hr Post-dose, n=14, 14 | 269.3 Micromoles per liter (µmol/L) | Standard Deviation 68.09 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Uric acid, SA, Pre-dose, n=6, 7 | 270.0 Micromoles per liter (µmol/L) | Standard Deviation 30.61 |
| Placebo | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Uric acid, SA, 1 hr Post-dose, n=7, 7 | 275.4 Micromoles per liter (µmol/L) | Standard Deviation 43.08 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Uric acid, SA, 1 hr Post-dose, n=7, 7 | 257.7 Micromoles per liter (µmol/L) | Standard Deviation 65.8 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Direct bilirubin, FA, Pre-dose, n=13, 11 | 1.64 Micromoles per liter (µmol/L) | Standard Deviation 0.809 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Creatinine, FA, Pre-dose, n=16, 14 | 64.0 Micromoles per liter (µmol/L) | Standard Deviation 11.21 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Direct bilirubin, FA, 1 hr Post-dose, n=10, 11 | 1.45 Micromoles per liter (µmol/L) | Standard Deviation 0.522 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Uric acid, FA, Pre-dose, n=16, 14 | 272.8 Micromoles per liter (µmol/L) | Standard Deviation 59.36 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Direct bilirubin, SA, Pre-dose, n=4, 6 | 1.83 Micromoles per liter (µmol/L) | Standard Deviation 0.753 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Creatinine, FA, 1 hr Post-dose, n=14, 14 | 60.5 Micromoles per liter (µmol/L) | Standard Deviation 8.49 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Direct bilirubin, SA, 1 hr Post-dose, n=5, 6 | 1.50 Micromoles per liter (µmol/L) | Standard Deviation 0.548 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Uric acid, SA, Pre-dose, n=6, 7 | 273.7 Micromoles per liter (µmol/L) | Standard Deviation 74.4 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Total bilirubin, FA, Pre-dose, n=16, 14 | 8.04 Micromoles per liter (µmol/L) | Standard Deviation 3.709 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Creatinine, SA, Pre-dose, n=6, 7 | 66.5 Micromoles per liter (µmol/L) | Standard Deviation 11.72 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Total bilirubin, FA, 1 hr Post-dose, n=14, 14 | 6.34 Micromoles per liter (µmol/L) | Standard Deviation 2.453 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Uric acid, FA, 1 hr Post-dose, n=14, 14 | 259.2 Micromoles per liter (µmol/L) | Standard Deviation 57.65 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Total bilirubin, SA, Pre-dose, n=6, 7 | 7.71 Micromoles per liter (µmol/L) | Standard Deviation 2.928 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Creatinine, SA, 1 hr Post-dose, n=7, 7 | 65.1 Micromoles per liter (µmol/L) | Standard Deviation 7.83 |
| GSK2339345 1000 Microgram (mcg) | Mean Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid Values at the Indicated Time Points in Part A | Total bilirubin, SA, 1 hr Post-dose, n=7, 7 | 5.87 Micromoles per liter (µmol/L) | Standard Deviation 1.928 |
Secondary
Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C
Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured by spirometry at pre-dose and 30 min after FA and SA in Part A and each administration in Parts B, and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 30 min post each dose administered in Parts A, B and C (up to 8 Weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, Pre-dose, n=16, 14 | 2.55 Liters | Standard Deviation 2.18 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 2.49 Liters | Standard Deviation 2.12 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, Pre-dose, n=16, 14 | 2.55 Liters | Standard Deviation 2.22 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 30 min Post-dose, n=15, 13 | 2.44 Liters | Standard Deviation 2.06 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, Pre-dose, n=7, 7 | 2.54 Liters | Standard Deviation 2.16 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 2.42 Liters | Standard Deviation 2 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, Pre-dose, n=7, 7 | 2.41 Liters | Standard Deviation 1.99 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 2.42 Liters | Standard Deviation 1.97 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part B, Pre-dose, n=10, 11 | 2.26 Liters | Standard Deviation 2.07 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part B, 30 min Post-dose, n=10, 11 | 2.17 Liters | Standard Deviation 2.01 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part C, Pre-dose, n=9, 9 | 2.23 Liters | Standard Deviation 2.08 |
| Placebo | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part C, 30 min Post-dose, n=9, 9 | 2.13 Liters | Standard Deviation 1.96 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part C, Pre-dose, n=9, 9 | 2.24 Liters | Standard Deviation 1.98 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, Pre-dose, n=16, 14 | 2.43 Liters | Standard Deviation 2.17 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, Pre-dose, n=7, 7 | 2.36 Liters | Standard Deviation 1.83 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 2.39 Liters | Standard Deviation 2.1 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part B, 30 min Post-dose, n=10, 11 | 2.30 Liters | Standard Deviation 2.05 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, Pre-dose, n=16, 14 | 2.37 Liters | Standard Deviation 2.1 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 2.32 Liters | Standard Deviation 1.8 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 30 min Post-dose, n=15, 13 | 2.29 Liters | Standard Deviation 2.02 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part C, 30 min Post-dose, n=9, 9 | 2.22 Liters | Standard Deviation 1.98 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, Pre-dose, n=7, 7 | 2.44 Liters | Standard Deviation 1.97 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part B, Pre-dose, n=10, 11 | 2.31 Liters | Standard Deviation 2.05 |
| GSK2339345 1000 Microgram (mcg) | Mean Forced Expiratory Volume in One Second (FEV1) Values at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 2.31 Liters | Standard Deviation 1.76 |
Secondary
Mean Heart Rate at the Indicated Time Points in Parts A, B and C
Heart rate measurements were obtained at following time points: pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr after FA and SA in Part A and each dose administration in Parts B and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. Pre-Dose is the average of the triplicate readings taken at the pre-dose assessment.
Time frame: Pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr after each dose administered in Parts A, B and C (up to 8 weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 1 hr, n=7, 7 | 62.6 Beats per minute | Standard Deviation 8.81 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 15 min, n=16, 14 | 69.0 Beats per minute | Standard Deviation 7.8 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2 avg Pre-dose, n=7, 7 | 69.0 Beats per minute | Standard Deviation 7.84 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 5 min, n=16, 14 | 64.1 Beats per minute | Standard Deviation 7.5 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 5 min, n=7, 7 | 66.7 Beats per minute | Standard Deviation 9.16 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 30 min, n=16, 14 | 68.6 Beats per minute | Standard Deviation 9.25 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 15 min, n=7, 7 | 66.0 Beats per minute | Standard Deviation 7.37 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 1 hr, n=16, 14 | 62.6 Beats per minute | Standard Deviation 7.7 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 30 min, n=7, 7 | 65.1 Beats per minute | Standard Deviation 7.78 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 1hr, n=16, 14 | 68.5 Beats per minute | Standard Deviation 8.3 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 1hr, n=7, 7 | 65.7 Beats per minute | Standard Deviation 7.06 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 15 min, n=16, 14 | 64.0 Beats per minute | Standard Deviation 6.41 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part B, avg Pre-dose, n=10, 11 | 64.5 Beats per minute | Standard Deviation 6.21 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, avg Pre-dose, n=7, 7 | 66.8 Beats per minute | Standard Deviation 12.8 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part B, 5 min, n=10, 11 | 60.0 Beats per minute | Standard Deviation 6.18 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2 avg Pre-dose, n=16, 14 | 72.6 Beats per minute | Standard Deviation 9.27 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part B, 15 min, n=10, 11 | 59.4 Beats per minute | Standard Deviation 4.99 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 5 min, n=7, 7 | 61.3 Beats per minute | Standard Deviation 8.9 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part B, 1 hr, n=10, 11 | 58.6 Beats per minute | Standard Deviation 6.2 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, avg Pre-dose, n=16, 14 | 68.6 Beats per minute | Standard Deviation 7.44 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part C, avg Pre-dose, n=9, 9 | 62.4 Beats per minute | Standard Deviation 4.27 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 15 min, n=7, 7 | 60.3 Beats per minute | Standard Deviation 9.01 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part C, 5 min, n=9, 9 | 60.3 Beats per minute | Standard Deviation 9.31 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 5 min, n=16, 14 | 69.9 Beats per minute | Standard Deviation 7.29 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part C, 15 min, n=9, 9 | 60.8 Beats per minute | Standard Deviation 6.51 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 30 min, n=7, 7 | 59.1 Beats per minute | Standard Deviation 8.45 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part C, 1hr, n=9, 9 | 59.2 Beats per minute | Standard Deviation 6.5 |
| Placebo | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 30 min, n=16, 14 | 64.1 Beats per minute | Standard Deviation 10.6 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part C, 1hr, n=9, 9 | 61.1 Beats per minute | Standard Deviation 6.47 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, avg Pre-dose, n=16, 14 | 66.3 Beats per minute | Standard Deviation 9.9 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 15 min, n=16, 14 | 64.9 Beats per minute | Standard Deviation 9.57 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 30 min, n=16, 14 | 61.8 Beats per minute | Standard Deviation 8.75 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 1 hr, n=16, 14 | 61.6 Beats per minute | Standard Deviation 7.88 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2 avg Pre-dose, n=16, 14 | 69.4 Beats per minute | Standard Deviation 11.82 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 5 min, n=16, 14 | 69.7 Beats per minute | Standard Deviation 12.02 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 15 min, n=16, 14 | 68.3 Beats per minute | Standard Deviation 9.52 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 30 min, n=16, 14 | 68.5 Beats per minute | Standard Deviation 13.39 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 2, 1hr, n=16, 14 | 67.6 Beats per minute | Standard Deviation 11.57 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, avg Pre-dose, n=7, 7 | 69.6 Beats per minute | Standard Deviation 8.33 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 5 min, n=7, 7 | 65.4 Beats per minute | Standard Deviation 8.08 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 15 min, n=7, 7 | 62.9 Beats per minute | Standard Deviation 6.82 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 30 min, n=7, 7 | 62.4 Beats per minute | Standard Deviation 7.16 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 1, 1 hr, n=7, 7 | 62.4 Beats per minute | Standard Deviation 6.35 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2 avg Pre-dose, n=7, 7 | 70.6 Beats per minute | Standard Deviation 6.2 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 5 min, n=7, 7 | 71.1 Beats per minute | Standard Deviation 8.19 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 15 min, n=7, 7 | 69.6 Beats per minute | Standard Deviation 10.05 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 30 min, n=7, 7 | 65.7 Beats per minute | Standard Deviation 6.99 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, SA, Dose 2, 1hr, n=7, 7 | 68.6 Beats per minute | Standard Deviation 8.3 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part B, avg Pre-dose, n=10, 11 | 68.4 Beats per minute | Standard Deviation 8.85 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part B, 5 min, n=10, 11 | 65.9 Beats per minute | Standard Deviation 8.87 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part B, 15 min, n=10, 11 | 63.5 Beats per minute | Standard Deviation 6.52 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part B, 1 hr, n=10, 11 | 61.0 Beats per minute | Standard Deviation 6.07 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part C, avg Pre-dose, n=9, 9 | 66.3 Beats per minute | Standard Deviation 7.07 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part C, 5 min, n=9, 9 | 65.0 Beats per minute | Standard Deviation 9.15 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part C, 15 min, n=9, 9 | 60.7 Beats per minute | Standard Deviation 5.5 |
| GSK2339345 1000 Microgram (mcg) | Mean Heart Rate at the Indicated Time Points in Parts A, B and C | Part A, FA, Dose 1, 5 min, n=16, 14 | 66.5 Beats per minute | Standard Deviation 10.06 |
Secondary
Mean Hematocrit Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of hematocrit at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All subject population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Hematocrit Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 0.4126 Proportion of one | Standard Deviation 0.03824 |
| Placebo | Mean Hematocrit Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=14, 13 | 0.3979 Proportion of one | Standard Deviation 0.03595 |
| Placebo | Mean Hematocrit Values at the Indicated Time Points in Part A | SA, Pre-dose, n=6, 7 | 0.3895 Proportion of one | Standard Deviation 0.02894 |
| Placebo | Mean Hematocrit Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 0.3826 Proportion of one | Standard Deviation 0.03321 |
| GSK2339345 1000 Microgram (mcg) | Mean Hematocrit Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 0.4010 Proportion of one | Standard Deviation 0.03316 |
| GSK2339345 1000 Microgram (mcg) | Mean Hematocrit Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 0.4119 Proportion of one | Standard Deviation 0.04143 |
| GSK2339345 1000 Microgram (mcg) | Mean Hematocrit Values at the Indicated Time Points in Part A | SA, Pre-dose, n=6, 7 | 0.4120 Proportion of one | Standard Deviation 0.0395 |
| GSK2339345 1000 Microgram (mcg) | Mean Hematocrit Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=14, 13 | 0.3973 Proportion of one | Standard Deviation 0.03701 |
Secondary
Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of hemoglobin, MCHC, albumin and total protein at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All subject population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Hemoglobin, FA, Pre-dose, n=16, 14 | 134.1 Grams per liter (G/L) | Standard Deviation 11.16 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Hemoglobin, FA, 1 hr Post-dose, n=14, 13 | 130.1 Grams per liter (G/L) | Standard Deviation 11.35 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Hemoglobin, SA, Pre-dose, n=6, 7 | 127.5 Grams per liter (G/L) | Standard Deviation 8.69 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Hemoglobin, SA, 1 hr Post-dose, n=7, 7 | 125.4 Grams per liter (G/L) | Standard Deviation 9.64 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | MCHC, FA, Pre-dose, n=16, 14 | 325.6 Grams per liter (G/L) | Standard Deviation 5.76 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | MCHC, FA, 1 hr Post-dose, n=14, 13 | 327.0 Grams per liter (G/L) | Standard Deviation 4.91 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | MCHC, SA, Pre-dose, n=6, 7 | 327.5 Grams per liter (G/L) | Standard Deviation 7.2 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | MCHC, SA, 1 hr Post-dose, n=7, 7 | 327.7 Grams per liter (G/L) | Standard Deviation 5.09 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Albumin, FA, Pre-dose, n=16, 14 | 43.4 Grams per liter (G/L) | Standard Deviation 3.1 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Albumin, FA, 1 hr Post-dose, n=14, 14 | 41.7 Grams per liter (G/L) | Standard Deviation 2.23 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Albumin, SA, Pre-dose, n=6, 7 | 43.3 Grams per liter (G/L) | Standard Deviation 3.27 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Albumin, SA, 1 hr Post-dose, n=7, 7 | 41.4 Grams per liter (G/L) | Standard Deviation 2.3 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Total protein, FA, Pre-dose, n=16, 14 | 69.3 Grams per liter (G/L) | Standard Deviation 4.32 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Total protein, FA, 1 hr Post-dose, n=14, 14 | 66.1 Grams per liter (G/L) | Standard Deviation 3.35 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Total protein, SA, Pre-dose, n=6, 7 | 69.0 Grams per liter (G/L) | Standard Deviation 4.69 |
| Placebo | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Total protein, SA, 1 hr Post-dose, n=7, 7 | 65.4 Grams per liter (G/L) | Standard Deviation 4.16 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Total protein, SA, 1 hr Post-dose, n=7, 7 | 66.0 Grams per liter (G/L) | Standard Deviation 3.61 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Hemoglobin, FA, Pre-dose, n=16, 14 | 134.2 Grams per liter (G/L) | Standard Deviation 11.82 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Albumin, FA, Pre-dose, n=16, 14 | 43.1 Grams per liter (G/L) | Standard Deviation 2.11 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Hemoglobin, FA, 1 hr Post-dose, n=14, 13 | 130.5 Grams per liter (G/L) | Standard Deviation 11.17 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Total protein, FA, Pre-dose, n=16, 14 | 68.5 Grams per liter (G/L) | Standard Deviation 2.41 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Hemoglobin, SA, Pre-dose, n=6, 7 | 133.4 Grams per liter (G/L) | Standard Deviation 10.34 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Albumin, FA, 1 hr Post-dose, n=14, 14 | 41.6 Grams per liter (G/L) | Standard Deviation 1.82 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Hemoglobin, SA, 1 hr Post-dose, n=7, 7 | 129.6 Grams per liter (G/L) | Standard Deviation 9.78 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Total protein, SA, Pre-dose, n=6, 7 | 69.1 Grams per liter (G/L) | Standard Deviation 3.34 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | MCHC, FA, Pre-dose, n=16, 14 | 326.3 Grams per liter (G/L) | Standard Deviation 6.14 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Albumin, SA, Pre-dose, n=6, 7 | 43.6 Grams per liter (G/L) | Standard Deviation 2.15 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | MCHC, FA, 1 hr Post-dose, n=14, 13 | 329.2 Grams per liter (G/L) | Standard Deviation 5.36 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Total protein, FA, 1 hr Post-dose, n=14, 14 | 66.6 Grams per liter (G/L) | Standard Deviation 2.41 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | MCHC, SA, Pre-dose, n=6, 7 | 324.0 Grams per liter (G/L) | Standard Deviation 6.51 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | Albumin, SA, 1 hr Post-dose, n=7, 7 | 41.6 Grams per liter (G/L) | Standard Deviation 1.99 |
| GSK2339345 1000 Microgram (mcg) | Mean Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC), Albumin and Total Protein Values at the Indicated Time Points in Part A | MCHC, SA, 1 hr Post-dose, n=7, 7 | 323.3 Grams per liter (G/L) | Standard Deviation 10.24 |
Secondary
Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B)
Capsaicin was administered using a dosimeter through a nebulizer pot with flow-limitation. Inhalation of increased concentrations (Conc.) was continued until the maximum dose was tolerated by the par. or highest available Conc. was used. The dose-response relationship between dose of capsaicin and cough response was investigated using non-linear mixed effect modeling using Poisson and Negative Binomial distributions. When using a Poisson distribution, there was some evidence for a reduction in capsaicin Emax with GSK2339345 of 17.6%, however, this was not confirmed when using a Negative Binomial distribution. The Negative Binomial distribution described the data marginally better, but the dataset was too small to make definitive conclusions. There was no treatment difference in capsaicin ED50.
Time frame: After the administration of GSK2339345 or placebo (first and second 15 seconds following each dose) at Visits 4 and 5 in Part B (up to 2 weeks)
Population: CC population. Population comprised of par. in the All Subjects Population for whom any CC data were available for one or both Part B study visits. Only those participants available at the specified time points we re analyze d (represented by n=X, X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 31.25 µmol/L, n=10, 11 | 8.7 Cough count | Standard Deviation 6.63 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc.0.97 µmol/L, n=10, 11 | 0.0 Cough count | Standard Deviation 0 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc.1.95 µmol/L, n=10, 11 | 2.0 Cough count | Standard Deviation 4.64 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc.3.9 µmol/L, n=10, 11 | 4.7 Cough count | Standard Deviation 5.79 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 7.81 µmol/L, n=10, 11 | 5.1 Cough count | Standard Deviation 6.45 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 15.62 µmol/L, n=10, 11 | 8.3 Cough count | Standard Deviation 5.96 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc.0.49 µmol/L, n=10, 11 | 0.0 Cough count | Standard Deviation 0 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 62.5 µmol/L, n=6, 10 | 8.3 Cough count | Standard Deviation 6.15 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 125 µmol/L, n=5, 9 | 6.0 Cough count | Standard Deviation 1.22 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 250 µmol/L, n=3, 6 | 6.3 Cough count | Standard Deviation 0.58 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 500 µmol/L, n=3, 4 | 7.3 Cough count | Standard Deviation 2.52 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 1000 µmol/L, n=1, 1 | 6.0 Cough count | — |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc.0.49 µmol/L, n=10, 11 | 0.0 Cough count | Standard Deviation 0 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc.0.97 µmol/L, n=10, 11 | 0.0 Cough count | Standard Deviation 0 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc.1.95 µmol/L, n=10, 11 | 2.0 Cough count | Standard Deviation 4.64 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc.3.9 µmol/L, n=10, 11 | 5.4 Cough count | Standard Deviation 6.59 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 7.81 µmol/L, n=10, 11 | 6.7 Cough count | Standard Deviation 9.57 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 15.62 µmol/L, n=10, 11 | 12.2 Cough count | Standard Deviation 9.47 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 31.25 µmol/L, n=10, 11 | 11.0 Cough count | Standard Deviation 9.87 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 62.5 µmol/L, n=6, 10 | 9.2 Cough count | Standard Deviation 7.19 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 125 µmol/L, n=5, 9 | 6.0 Cough count | Standard Deviation 1.22 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 250 µmol/L, n=3, 6 | 6.3 Cough count | Standard Deviation 0.58 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 500 µmol/L, n=3, 4 | 8.7 Cough count | Standard Deviation 4.73 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 1000 µmol/L, n=1, 1 | 6.0 Cough count | — |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 500 µmol/L, n=3, 4 | 8.5 Cough count | Standard Deviation 3.51 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc.0.49 µmol/L, n=10, 11 | 0.3 Cough count | Standard Deviation 0.9 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc.0.49 µmol/L, n=10, 11 | 0.5 Cough count | Standard Deviation 1.81 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc.0.97 µmol/L, n=10, 11 | 0.2 Cough count | Standard Deviation 0.6 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 31.25 µmol/L, n=10, 11 | 6.5 Cough count | Standard Deviation 5.01 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc.1.95 µmol/L, n=10, 11 | 1.8 Cough count | Standard Deviation 3.19 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc.0.97 µmol/L, n=10, 11 | 0.2 Cough count | Standard Deviation 0.6 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc.3.9 µmol/L, n=10, 11 | 3.3 Cough count | Standard Deviation 6.2 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 250 µmol/L, n=3, 6 | 6.7 Cough count | Standard Deviation 1.37 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 7.81 µmol/L, n=10, 11 | 5.3 Cough count | Standard Deviation 6.08 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc.1.95 µmol/L, n=10, 11 | 1.9 Cough count | Standard Deviation 3.36 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 15.62 µmol/L, n=10, 11 | 6.9 Cough count | Standard Deviation 4.66 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 62.5 µmol/L, n=6, 10 | 7.4 Cough count | Standard Deviation 4.12 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 31.25 µmol/L, n=10, 11 | 6.0 Cough count | Standard Deviation 4.36 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc.3.9 µmol/L, n=10, 11 | 4.3 Cough count | Standard Deviation 6.83 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 62.5 µmol/L, n=6, 10 | 6.8 Cough count | Standard Deviation 3.55 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 1000 µmol/L, n=1, 1 | 7.0 Cough count | — |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 125 µmol/L, n=5, 9 | 7.1 Cough count | Standard Deviation 3.02 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 7.81 µmol/L, n=10, 11 | 5.5 Cough count | Standard Deviation 6.42 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 250 µmol/L, n=3, 6 | 5.7 Cough count | Standard Deviation 1.21 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 125 µmol/L, n=5, 9 | 8.2 Cough count | Standard Deviation 4.24 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 500 µmol/L, n=3, 4 | 7.3 Cough count | Standard Deviation 2.22 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 30 sec, CC Conc. 15.62 µmol/L, n=10, 11 | 7.5 Cough count | Standard Deviation 5.47 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Capsaicin Challenge (CC) at Visits 4 and 5 (Part B) | 0 to 15 sec, CC Conc. 1000 µmol/L, n=1, 1 | 7.0 Cough count | — |
Secondary
Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C)
Citric acid was administered using a dosimeter through a nebulizer pot with flow-limitation. Inhalation of increased Conc. was continued until the maximum dose was tolerated by the par. or the highest available Conc. was used. The dose-response relationship between the dose of citric acid and cough response was investigated using non-linear mixed effect modelling using Poisson and Negative Binomial distributions. When using a Poisson distribution, there was some evidence for an increase in citric acid ED50 with GSK2339345 of 41.6%, however, this was not confirmed when using a Negative Binomial distribution. The Negative Binomial distribution described the data marginally better, but the dataset was too small to make definitive conclusions. There was no treatment difference in citric acid Emax
Time frame: After the administration of GSK2339345 or placebo (first and second 15 seconds following each dose) at Visits 6 and 7 in Part C (up to 2 weeks)
Population: CAC Population comprised of participants in the All Subjects Population for whom any CAC data were available for one or both Part C study visits. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.03 mol/L, n=9, 9 | 0.2 Cough count | Standard Deviation 0.44 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.06 mol/L, n=9, 9 | 0.2 Cough count | Standard Deviation 0.67 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.125 mol/L, n=9, 9 | 3.0 Cough count | Standard Deviation 4.66 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.25 mol/L, n=9, 9 | 3.7 Cough count | Standard Deviation 4.09 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.5 mol/L, n=9, 9 | 6.1 Cough count | Standard Deviation 5.13 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 1 mol/L, n=9, 9 | 6.0 Cough count | Standard Deviation 3.5 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 2 mol/L, n=5,7 | 5.8 Cough count | Standard Deviation 4.02 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 4 mol/L, n=5, 6 | 4.0 Cough count | Standard Deviation 3.81 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.03 mol/L, n=9, 9 | 0.2 Cough count | Standard Deviation 0.44 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.06 mol/L, n=9, 9 | 0.2 Cough count | Standard Deviation 0.67 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.125 mol/L, n=9, 9 | 3.2 Cough count | Standard Deviation 4.55 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.25 mol/L, n=9, 9 | 4.6 Cough count | Standard Deviation 6 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.5 mol/L, n=9, 9 | 7.3 Cough count | Standard Deviation 6.34 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 1 mol/L, n=9, 9 | 7.2 Cough count | Standard Deviation 4.55 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 2 mol/L, n=5, 7 | 6.8 Cough count | Standard Deviation 4.82 |
| Placebo | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 4 mol/L, n=5, 6 | 4.8 Cough count | Standard Deviation 3.83 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 4 mol/L, n=5, 6 | 6.2 Cough count | Standard Deviation 5.34 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.03 mol/L, n=9, 9 | 0.2 Cough count | Standard Deviation 0.67 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.03 mol/L, n=9, 9 | 0.2 Cough count | Standard Deviation 0.67 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.06 mol/L, n=9, 9 | 0.6 Cough count | Standard Deviation 1.33 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.5 mol/L, n=9, 9 | 5.0 Cough count | Standard Deviation 4.09 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.125 mol/L, n=9, 9 | 1.8 Cough count | Standard Deviation 1.92 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.06 mol/L, n=9, 9 | 0.6 Cough count | Standard Deviation 1.33 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.25 mol/L, n=9, 9 | 2.7 Cough count | Standard Deviation 3.43 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 2 mol/L, n=5, 7 | 6.4 Cough count | Standard Deviation 5.32 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 0.5 mol/L, n=9, 9 | 4.3 Cough count | Standard Deviation 3.43 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.125 mol/L, n=9, 9 | 2.0 Cough count | Standard Deviation 2.06 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 1 mol/L, n=9, 9 | 6.6 Cough count | Standard Deviation 3.4 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 1 mol/L, n=9, 9 | 9.3 Cough count | Standard Deviation 6.32 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 2 mol/L, n=5,7 | 4.1 Cough count | Standard Deviation 3.29 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 30 sec, CAC Conc. 0.25 mol/L, n=9, 9 | 2.7 Cough count | Standard Deviation 3.43 |
| GSK2339345 1000 Microgram (mcg) | Mean Number of Cough Counts at Each Dose of the Challenge Agent for the Citric Acid Challenge (CAC)at Visits 6 and 7 (Part C) | 0 to 15 sec, CAC Conc. 4 mol/L, n=5, 6 | 5.3 Cough count | Standard Deviation 4.46 |
Secondary
Mean Red Blood Cell Count Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of red blood cell count at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All subject population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 4.52 10^12 cells per liter (TI/L) | Standard Deviation 0.452 |
| Placebo | Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | SA, Pre-dose, n=6, 7 | 4.34 10^12 cells per liter (TI/L) | Standard Deviation 0.296 |
| Placebo | Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=14, 13 | 4.40 10^12 cells per liter (TI/L) | Standard Deviation 0.47 |
| Placebo | Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 4.24 10^12 cells per liter (TI/L) | Standard Deviation 0.436 |
| GSK2339345 1000 Microgram (mcg) | Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=14, 13 | 4.39 10^12 cells per liter (TI/L) | Standard Deviation 0.46 |
| GSK2339345 1000 Microgram (mcg) | Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 4.54 10^12 cells per liter (TI/L) | Standard Deviation 0.553 |
| GSK2339345 1000 Microgram (mcg) | Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 4.42 10^12 cells per liter (TI/L) | Standard Deviation 0.406 |
| GSK2339345 1000 Microgram (mcg) | Mean Red Blood Cell Count Values at the Indicated Time Points in Part A | SA, Pre-dose, n=6, 7 | 4.51 10^12 cells per liter (TI/L) | Standard Deviation 0.522 |
Secondary
Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were obtained at following time points: pre-dose, 5 minutes (min), 15 min (only in Part A), 30 min, and 1 hr after first administration (FA) and second administration (SA) in Part A and each dose administration of Parts B and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. Pre-Dose is the average (avg) of the triplicate readings taken at the pre-dose assessment.
Time frame: Pre-dose, 5 min, 15 min (only in Part A), 30 min, and 1 hr post each dose administered in Parts A, B and C (up to 8 weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, 1 hr, n=7, 7 | 134.4 Millimeter of mercury (mmHg) | Standard Deviation 17.82 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, 5 min, n=16, 14 | 125.5 Millimeter of mercury (mmHg) | Standard Deviation 14.37 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, 15 min, n=16, 14 | 125.3 Millimeter of mercury (mmHg) | Standard Deviation 14.06 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, 30 min, n=16, 14 | 125.6 Millimeter of mercury (mmHg) | Standard Deviation 14.12 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, 1 hr, n=16, 14 | 126.1 Millimeter of mercury (mmHg) | Standard Deviation 15.66 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2 avg Pre-dose, n=16, 14 | 117.8 Millimeter of mercury (mmHg) | Standard Deviation 10.95 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2, 5 min, n=15, 14 | 120.6 Millimeter of mercury (mmHg) | Standard Deviation 13.21 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2, 15 min, n=15, 14 | 120.7 Millimeter of mercury (mmHg) | Standard Deviation 12.96 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2, 30 min, n=15, 14 | 120.8 Millimeter of mercury (mmHg) | Standard Deviation 11.97 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2, 1hr, n=15, 14 | 124.5 Millimeter of mercury (mmHg) | Standard Deviation 13.68 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, avg Pre-dose, n=7, 7 | 130.8 Millimeter of mercury (mmHg) | Standard Deviation 15.43 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, 5 min, n=7, 7 | 127.7 Millimeter of mercury (mmHg) | Standard Deviation 16.23 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, 15 min, n=7, 7 | 125.1 Millimeter of mercury (mmHg) | Standard Deviation 22.35 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, 30 min, n=7, 7 | 128.0 Millimeter of mercury (mmHg) | Standard Deviation 18.83 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, avg Pre-dose, n=16, 14 | 126.1 Millimeter of mercury (mmHg) | Standard Deviation 14.09 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2 avg Pre-dose, n=7, 7 | 125.0 Millimeter of mercury (mmHg) | Standard Deviation 11.95 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2, 5 min, n=7, 7 | 125.4 Millimeter of mercury (mmHg) | Standard Deviation 16.29 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2, 15 min, n=7, 7 | 118.9 Millimeter of mercury (mmHg) | Standard Deviation 12.4 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2, 30 min, n=7, 7 | 119.0 Millimeter of mercury (mmHg) | Standard Deviation 11.72 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2, 1hr, n=7, 7 | 129.9 Millimeter of mercury (mmHg) | Standard Deviation 19.27 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part B, avg Pre-dose, n=10, 11 | 119.2 Millimeter of mercury (mmHg) | Standard Deviation 11.69 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part B, 5 min, n=10, 11 | 119.6 Millimeter of mercury (mmHg) | Standard Deviation 11.24 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part B, 15 min, n=10, 11 | 121.5 Millimeter of mercury (mmHg) | Standard Deviation 15.23 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part B, 1 hr, n=10, 11 | 124.2 Millimeter of mercury (mmHg) | Standard Deviation 17 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part C, avg Pre-dose, n=9, 9 | 125.2 Millimeter of mercury (mmHg) | Standard Deviation 11.37 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part C, 5 min, n=9, 9 | 125.6 Millimeter of mercury (mmHg) | Standard Deviation 14.75 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part C, 15 min, n=9, 9 | 121.6 Millimeter of mercury (mmHg) | Standard Deviation 12.24 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part C, 1hr, n=9, 9 | 127.1 Millimeter of mercury (mmHg) | Standard Deviation 15.34 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, avg Pre-dose, n=16, 14 | 68.8 Millimeter of mercury (mmHg) | Standard Deviation 7.23 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, 5 min, n=16, 14 | 72.3 Millimeter of mercury (mmHg) | Standard Deviation 6.88 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, 15 min, n=16, 14 | 69.6 Millimeter of mercury (mmHg) | Standard Deviation 7.8 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, 30 min, n=16, 14 | 71.6 Millimeter of mercury (mmHg) | Standard Deviation 10.03 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, 1 hr, n=16, 14 | 70.9 Millimeter of mercury (mmHg) | Standard Deviation 7.53 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2 avg Pre-dose, n=16, 14 | 64.6 Millimeter of mercury (mmHg) | Standard Deviation 5.7 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2, 5 min, n=15, 14 | 66.3 Millimeter of mercury (mmHg) | Standard Deviation 7.69 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2, 15 min, n=15, 14 | 65.5 Millimeter of mercury (mmHg) | Standard Deviation 7.9 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2, 30 min, n=15, 14 | 66.7 Millimeter of mercury (mmHg) | Standard Deviation 7.21 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2, 1hr, n=15, 14 | 68.4 Millimeter of mercury (mmHg) | Standard Deviation 6.46 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, avg Pre-dose, n=7, 7 | 70.2 Millimeter of mercury (mmHg) | Standard Deviation 5.74 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, 5 min, n=7, 7 | 68.9 Millimeter of mercury (mmHg) | Standard Deviation 6.2 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, 15 min, n=7, 7 | 68.6 Millimeter of mercury (mmHg) | Standard Deviation 4.54 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, 30 min, n=7, 7 | 67.0 Millimeter of mercury (mmHg) | Standard Deviation 5.72 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, 1 hr, n=7, 7 | 72.4 Millimeter of mercury (mmHg) | Standard Deviation 7 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2 avg Pre-dose, n=7, 7 | 67.3 Millimeter of mercury (mmHg) | Standard Deviation 5.95 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2, 5 min, n=7, 7 | 65.1 Millimeter of mercury (mmHg) | Standard Deviation 5.98 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2, 15 min, n=7, 7 | 64.4 Millimeter of mercury (mmHg) | Standard Deviation 5.91 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2, 30 min, n=7, 7 | 63.4 Millimeter of mercury (mmHg) | Standard Deviation 6.73 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2, 1hr, n=7, 7 | 69.1 Millimeter of mercury (mmHg) | Standard Deviation 7.9 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part B, avg Pre-dose, n=10, 11 | 63.9 Millimeter of mercury (mmHg) | Standard Deviation 4.74 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part B, 5 min, n=10, 11 | 63.9 Millimeter of mercury (mmHg) | Standard Deviation 3.31 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part B, 15 min, n=10, 11 | 64.9 Millimeter of mercury (mmHg) | Standard Deviation 6.51 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part B, 1 hr, n=10, 11 | 64.3 Millimeter of mercury (mmHg) | Standard Deviation 6.99 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part C, avg Pre-dose, n=9, 9 | 64.9 Millimeter of mercury (mmHg) | Standard Deviation 5.5 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part C, 5 min, n=9, 9 | 68.0 Millimeter of mercury (mmHg) | Standard Deviation 7.37 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part C, 15 min, n=9, 9 | 65.7 Millimeter of mercury (mmHg) | Standard Deviation 4.03 |
| Placebo | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part C, 1hr, n=9, 9 | 65.4 Millimeter of mercury (mmHg) | Standard Deviation 6.31 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part C, avg Pre-dose, n=9, 9 | 68.0 Millimeter of mercury (mmHg) | Standard Deviation 8.68 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, avg Pre-dose, n=16, 14 | 123.3 Millimeter of mercury (mmHg) | Standard Deviation 15.02 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, avg Pre-dose, n=16, 14 | 69.1 Millimeter of mercury (mmHg) | Standard Deviation 4.61 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, 5 min, n=16, 14 | 130.2 Millimeter of mercury (mmHg) | Standard Deviation 17.16 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, 1 hr, n=7, 7 | 69.1 Millimeter of mercury (mmHg) | Standard Deviation 6.49 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, 15 min, n=16, 14 | 124.1 Millimeter of mercury (mmHg) | Standard Deviation 14.44 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, 5 min, n=16, 14 | 71.6 Millimeter of mercury (mmHg) | Standard Deviation 5.33 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, 30 min, n=16, 14 | 124.1 Millimeter of mercury (mmHg) | Standard Deviation 17.67 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part B, 5 min, n=10, 11 | 66.5 Millimeter of mercury (mmHg) | Standard Deviation 3.67 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 1, 1 hr, n=16, 14 | 123.6 Millimeter of mercury (mmHg) | Standard Deviation 13.74 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, 15 min, n=16, 14 | 70.6 Millimeter of mercury (mmHg) | Standard Deviation 6.2 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2 avg Pre-dose, n=16, 14 | 119.5 Millimeter of mercury (mmHg) | Standard Deviation 11.42 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2 avg Pre-dose, n=7, 7 | 63.3 Millimeter of mercury (mmHg) | Standard Deviation 2.89 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2, 5 min, n=15, 14 | 128.1 Millimeter of mercury (mmHg) | Standard Deviation 18.58 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, 30 min, n=16, 14 | 69.5 Millimeter of mercury (mmHg) | Standard Deviation 7.34 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2, 15 min, n=15, 14 | 123.0 Millimeter of mercury (mmHg) | Standard Deviation 16.15 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part C, 15 min, n=9, 9 | 65.7 Millimeter of mercury (mmHg) | Standard Deviation 7.09 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2, 30 min, n=15, 14 | 118.2 Millimeter of mercury (mmHg) | Standard Deviation 12.91 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 1, 1 hr, n=16, 14 | 69.9 Millimeter of mercury (mmHg) | Standard Deviation 5.14 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, FA, Dose 2, 1hr, n=15, 14 | 121.5 Millimeter of mercury (mmHg) | Standard Deviation 11.31 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2, 5 min, n=7, 7 | 67.0 Millimeter of mercury (mmHg) | Standard Deviation 4.97 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, avg Pre-dose, n=7, 7 | 121.2 Millimeter of mercury (mmHg) | Standard Deviation 8.25 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2 avg Pre-dose, n=16, 14 | 65.2 Millimeter of mercury (mmHg) | Standard Deviation 6.55 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, 5 min, n=7, 7 | 124.1 Millimeter of mercury (mmHg) | Standard Deviation 11.17 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part B, 15 min, n=10, 11 | 66.2 Millimeter of mercury (mmHg) | Standard Deviation 6 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, 15 min, n=7, 7 | 117.9 Millimeter of mercury (mmHg) | Standard Deviation 9.74 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2, 5 min, n=15, 14 | 66.4 Millimeter of mercury (mmHg) | Standard Deviation 7.69 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, 30 min, n=7, 7 | 119.3 Millimeter of mercury (mmHg) | Standard Deviation 10.21 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2, 15 min, n=7, 7 | 64.0 Millimeter of mercury (mmHg) | Standard Deviation 4.97 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 1, 1 hr, n=7, 7 | 122.4 Millimeter of mercury (mmHg) | Standard Deviation 13.13 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2, 15 min, n=15, 14 | 66.1 Millimeter of mercury (mmHg) | Standard Deviation 8.02 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2 avg Pre-dose, n=7, 7 | 112.4 Millimeter of mercury (mmHg) | Standard Deviation 8.54 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part C, 5 min, n=9, 9 | 65.6 Millimeter of mercury (mmHg) | Standard Deviation 5.98 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2, 5 min, n=7, 7 | 118.1 Millimeter of mercury (mmHg) | Standard Deviation 9.32 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2, 30 min, n=15, 14 | 67.1 Millimeter of mercury (mmHg) | Standard Deviation 6.95 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2, 15 min, n=7, 7 | 112.4 Millimeter of mercury (mmHg) | Standard Deviation 9.71 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2, 30 min, n=7, 7 | 66.3 Millimeter of mercury (mmHg) | Standard Deviation 5.25 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2, 30 min, n=7, 7 | 116.3 Millimeter of mercury (mmHg) | Standard Deviation 10.37 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, FA, Dose 2, 1hr, n=15, 14 | 69.6 Millimeter of mercury (mmHg) | Standard Deviation 8.78 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part A, SA, Dose 2, 1hr, n=7, 7 | 121.4 Millimeter of mercury (mmHg) | Standard Deviation 15.09 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part B, 1 hr, n=10, 11 | 66.2 Millimeter of mercury (mmHg) | Standard Deviation 2.82 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part B, avg Pre-dose, n=10, 11 | 124.0 Millimeter of mercury (mmHg) | Standard Deviation 10.42 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, avg Pre-dose, n=7, 7 | 70.6 Millimeter of mercury (mmHg) | Standard Deviation 7.93 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part B, 5 min, n=10, 11 | 123.9 Millimeter of mercury (mmHg) | Standard Deviation 13.88 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 2, 1hr, n=7, 7 | 71.3 Millimeter of mercury (mmHg) | Standard Deviation 5.82 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part B, 15 min, n=10, 11 | 118.7 Millimeter of mercury (mmHg) | Standard Deviation 10.86 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, 5 min, n=7, 7 | 67.9 Millimeter of mercury (mmHg) | Standard Deviation 4.45 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part B, 1 hr, n=10, 11 | 125.5 Millimeter of mercury (mmHg) | Standard Deviation 12.89 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part C, 1hr, n=9, 9 | 67.7 Millimeter of mercury (mmHg) | Standard Deviation 6.71 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part C, avg Pre-dose, n=9, 9 | 123.0 Millimeter of mercury (mmHg) | Standard Deviation 12.28 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, 15 min, n=7, 7 | 67.3 Millimeter of mercury (mmHg) | Standard Deviation 6.37 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part C, 5 min, n=9, 9 | 129.3 Millimeter of mercury (mmHg) | Standard Deviation 12.7 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part B, avg Pre-dose, n=10, 11 | 67.3 Millimeter of mercury (mmHg) | Standard Deviation 4.29 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part C, 15 min, n=9, 9 | 124.1 Millimeter of mercury (mmHg) | Standard Deviation 13.18 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | DBP, Part A, SA, Dose 1, 30 min, n=7, 7 | 68.7 Millimeter of mercury (mmHg) | Standard Deviation 3.3 |
| GSK2339345 1000 Microgram (mcg) | Mean Systolic Blood Pressure and Diastolic Blood Pressure at the Indicated Time Points in Parts A, B and C | SBP, Part C, 1hr, n=9, 9 | 135.9 Millimeter of mercury (mmHg) | Standard Deviation 21.77 |
Secondary
Mean Transient Cough Counts at the Indicated Time Points in Part A
Cough counts (8 hours of recording) was conducted at Visits 1, 2 and 3 (4 hours of post-dose recording for each of the two doses administered). Coughs was counted by a cough monitor fitted to the participants for 8 hours post Dose 1. Transient coughing was calculated as the total number of coughs experienced in the two minutes from the start of the first inhalation of a dose. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A
Time frame: 0-4 hr, 4-8 hr, 0-8 hr post each dose at Visits 1, 2 and 3 in Part A (up to 8 weeks)
Population: All Subjects Population.Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different time points, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Transient Cough Counts at the Indicated Time Points in Part A | FA, 4-8 hr, n=14, 14 | 0.9 Cough count | Standard Deviation 1.88 |
| Placebo | Mean Transient Cough Counts at the Indicated Time Points in Part A | SA, 0-4 hr, n=7, 7 | 0.0 Cough count | Standard Deviation 0 |
| Placebo | Mean Transient Cough Counts at the Indicated Time Points in Part A | FA, 0-4 hr, n=14, 14 | 1.7 Cough count | Standard Deviation 3.41 |
| Placebo | Mean Transient Cough Counts at the Indicated Time Points in Part A | FA, 0-8 hr, n=14, 14 | 2.6 Cough count | Standard Deviation 4.11 |
| Placebo | Mean Transient Cough Counts at the Indicated Time Points in Part A | SA, 0-8 hr, n=7, 7 | 2.0 Cough count | Standard Deviation 3.42 |
| Placebo | Mean Transient Cough Counts at the Indicated Time Points in Part A | SA, 4-8 hr, n=7, 7 | 2.0 Cough count | Standard Deviation 3.42 |
| GSK2339345 1000 Microgram (mcg) | Mean Transient Cough Counts at the Indicated Time Points in Part A | SA, 0-8 hr, n=7, 7 | 34.1 Cough count | Standard Deviation 24.83 |
| GSK2339345 1000 Microgram (mcg) | Mean Transient Cough Counts at the Indicated Time Points in Part A | FA, 0-4 hr, n=14, 14 | 17.8 Cough count | Standard Deviation 16.27 |
| GSK2339345 1000 Microgram (mcg) | Mean Transient Cough Counts at the Indicated Time Points in Part A | FA, 4-8 hr, n=14, 14 | 19.0 Cough count | Standard Deviation 10.91 |
| GSK2339345 1000 Microgram (mcg) | Mean Transient Cough Counts at the Indicated Time Points in Part A | FA, 0-8 hr, n=14, 14 | 36.8 Cough count | Standard Deviation 25.41 |
| GSK2339345 1000 Microgram (mcg) | Mean Transient Cough Counts at the Indicated Time Points in Part A | SA, 0-4 hr, n=7, 7 | 18.3 Cough count | Standard Deviation 13.51 |
| GSK2339345 1000 Microgram (mcg) | Mean Transient Cough Counts at the Indicated Time Points in Part A | SA, 4-8 hr, n=7, 7 | 15.9 Cough count | Standard Deviation 12.02 |
Secondary
Mean Troponin I Values at the Indicated Time Points in Part A
Blood samples were collected for the measurement of troponin I at pre-dose and 1 hr after each dose of FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. Cardiac troponin values that were below the quantification limit \[0.02 or 0.04 microgram (mcg/L)\] were imputed as 0.01 (mcg/L).
Time frame: Pre-dose and 1 hr post each dose administered in Part A (up to 3 Weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Troponin I Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 0.011 mcg/L | Standard Deviation 0.0034 |
| Placebo | Mean Troponin I Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=15, 13 | 0.010 mcg/L | Standard Deviation 0 |
| Placebo | Mean Troponin I Values at the Indicated Time Points in Part A | SA, Pre-dose, n=7, 7 | 0.010 mcg/L | Standard Deviation 0 |
| Placebo | Mean Troponin I Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 0.010 mcg/L | Standard Deviation 0 |
| GSK2339345 1000 Microgram (mcg) | Mean Troponin I Values at the Indicated Time Points in Part A | SA, 1 hr Post-dose, n=7, 7 | 0.010 mcg/L | Standard Deviation 0 |
| GSK2339345 1000 Microgram (mcg) | Mean Troponin I Values at the Indicated Time Points in Part A | FA, Pre-dose, n=16, 14 | 0.010 mcg/L | Standard Deviation 0 |
| GSK2339345 1000 Microgram (mcg) | Mean Troponin I Values at the Indicated Time Points in Part A | SA, Pre-dose, n=7, 7 | 0.010 mcg/L | Standard Deviation 0 |
| GSK2339345 1000 Microgram (mcg) | Mean Troponin I Values at the Indicated Time Points in Part A | FA, 1 hr Post-dose, n=15, 13 | 0.010 mcg/L | Standard Deviation 0 |
Secondary
Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A)
VAS for urge to cough and severity of cough were recorded prior to first dose and 1 hour following the second dose of GSK2339345 or placebo at Visits 1, 2 and 3.VAS is a 100-mm linear scales on which participants indicated the severity of their cough (0 mm represents no severity and 100 mm maximum severity ever experienced) and urge to cough (0 represents no urge to cough, 100 represents maximum urge to cough ever experienced). Mean of replicate values per participants used where the same treatment taken during different periods.
Time frame: Prior to first dose and 1hr post second dose at Visits 1, 2 and 3 in Part A (up to 3 weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Urge to cough, Dose 1, Pre-dose, n=16, 14 | 42.9 Scores on a scale | Standard Deviation 20.51 |
| Placebo | Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Urge to cough, Dose 2, 1 hr Post-dose, n=15, 14 | 25.1 Scores on a scale | Standard Deviation 15.4 |
| Placebo | Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Cough severity, Dose 1, Pre-dose, n=16, 14 | 42.8 Scores on a scale | Standard Deviation 16.71 |
| Placebo | Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Cough severity, Dose 2, 1 hr Post-dose, n=15, 14 | 26.7 Scores on a scale | Standard Deviation 15.03 |
| GSK2339345 1000 Microgram (mcg) | Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Cough severity, Dose 2, 1 hr Post-dose, n=15, 14 | 39.3 Scores on a scale | Standard Deviation 21.7 |
| GSK2339345 1000 Microgram (mcg) | Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Urge to cough, Dose 1, Pre-dose, n=16, 14 | 42.2 Scores on a scale | Standard Deviation 25.94 |
| GSK2339345 1000 Microgram (mcg) | Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Cough severity, Dose 1, Pre-dose, n=16, 14 | 37.3 Scores on a scale | Standard Deviation 23.03 |
| GSK2339345 1000 Microgram (mcg) | Mean Visual Analogue Scale (VAS) Score of Cough Severity and Urge to Cough at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | Urge to cough, Dose 2, 1 hr Post-dose, n=15, 14 | 41.5 Scores on a scale | Standard Deviation 22.6 |
Secondary
Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C
A 12-lead ECG was recorded in a seated position after the participant was kept at rest in this position for at least 10 minutes. ECGs were obtained at pre-dose and 5 min, 15 min (only in Part A) 30 min, and 1 hr after FA and SA in Part A and each administration in Parts B, and C. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. Data are presented as clinically significant (CS) or not clinically significant (NCS) abnormal findings any time during study. The study investigator determined if the abnormal ECG finding was CS or NCS.
Time frame: Pre-dose and 5min to 1 hr after each dose administered in Parts A, B and C (up to 8 Weeks)
Population: All subject population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, FA, Normal, n=16, 14 | 13 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, FA, Abnormal NCS, n=16, 14 | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, FA Abnormal CS, n=16, 14 | 1 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, SA, Normal, n=7, 7 | 4 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, SA, Abnormal NCS, n=7, 7 | 2 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, SA, Abnormal CS, n=7, 7 | 1 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part B, Normal, n=10, 11 | 9 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part B, Abnormal NCS, n=10, 11 | 1 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part B, Abnormal CS, n=10, 11 | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part C, Normal, n=9, 9 | 9 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part C, Abnormal NCS, n=9, 9 | 0 Participants |
| Placebo | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part C, Abnormal CS, n=9, 9 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part C, Abnormal NCS, n=9, 9 | 1 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, FA, Normal, n=16, 14 | 12 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part B, Normal, n=10, 11 | 10 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, FA, Abnormal NCS, n=16, 14 | 2 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part C, Normal, n=9, 9 | 8 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, FA Abnormal CS, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part B, Abnormal NCS, n=10, 11 | 1 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, SA, Normal, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part C, Abnormal CS, n=9, 9 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, SA, Abnormal NCS, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part B, Abnormal CS, n=10, 11 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings in Parts A, B and C | Part A, SA, Abnormal CS, n=7, 7 | 0 Participants |
Secondary
Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs)
An AE is defined as any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as 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, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Time frame: From the start of study treatment and until the follow-up contact (up to 8 Weeks)
Population: All Subjects Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | Any AE | 10 participants |
| Placebo | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | Any SAE | 0 participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | Any AE | 5 participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Any Adverse Events (AEs) and Any Serious Adverse Events (SAEs) | Any SAE | 0 participants |
Secondary
Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A
The perception of change in oropharyngeal sensation was assessed by a 4 point scale where participants were asked to describe sensitivity and perception of numbness and the responses were recorded. The following information was collected: 0 = no anaesthesia (A), 1 = mild anaesthesia, 2 = moderate anaesthesia and 3 = severe anaesthesia. Oropharyngeal examination was performed at 2 min, 5 min, 15 min, 30 min, 1 hr and 2 hr after FA and SA in Part A. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A
Time frame: From 2 min -2 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 8 weeks)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the All Subjects Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 2 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 5 min Post-dose, n=16, 14 | 16 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 15 min Post-dose, n=16, 14 | 16 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 16 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 1 hr Post-dose, n=16, 14 | 16 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 2 min Post-dose, n=15, 14 | 15 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 5 min Post-dose, n=15, 14 | 15 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 15 min Post-dose, n=15, 14 | 15 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 30 min Post-dose, n=15, 14 | 15 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 1 hr Post-dose, n=15, 14 | 15 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 2 min Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 5 min Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 15 min Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 1 hr Post-dose, n=7,7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 2 min Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 5 min Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 15 min Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 1 hr Post-dose, n=7, 7 | 7 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 2 min Post-dose, n=16, 14 | 16 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 5 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 15 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 1 hr Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 2 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 5 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 15 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 30 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 1 hr Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 2 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 5 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 15 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 1 hr Post-dose, n=7,7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 2 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 5 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 15 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 1 hr Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 2 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 5 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 15 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 1 hr Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 2 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 5 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 15 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 30 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 1 hr Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 2 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 5 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 15 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 1 hr Post-dose, n=7,7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 2 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 5 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 15 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 1 hr Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 2 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 5 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 15 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 1 hr Post-dose, n=16, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 2 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 5 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 15 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 30 min Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 1 hr Post-dose, n=15, 14 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 2 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 5 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 15 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 1 hr Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 2 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 5 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 15 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 0 Participants |
| Placebo | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 1 hr Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 15 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 2 min Post-dose, n=16, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 2 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 5 min Post-dose, n=16, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 2 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 15 min Post-dose, n=16, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 5 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 2 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 1, 1 hr Post-dose, n=16, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 15 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 2 min Post-dose, n=15, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 5 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 5 min Post-dose, n=15, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 15 min Post-dose, n=15, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 2 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 30 min Post-dose, n=15, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 1, 1 hr Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, FA, Dose 2, 1 hr Post-dose, n=15, 14 | 14 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 15 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 2 min Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 2 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 5 min Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 5 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 15 min Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 5 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 1, 1 hr Post-dose, n=7,7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 15 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 2 min Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 1 hr Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 5 min Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 30 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 15 min Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 1, 1 hr Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, FA, Dose 2, 1 hr Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | No A, SA, Dose 2, 1 hr Post-dose, n=7, 7 | 7 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 15 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 2 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 2 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 5 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 2 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 15 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 5 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 30 min Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 5 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 1, 1 hr Post-dose, n=16, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 15 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 2 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 5 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 5 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 15 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 30 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 1, 1 hr Post-dose, n=7,7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, FA, Dose 2, 1 hr Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 15 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 2 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 2 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 5 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 15 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 5 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 30 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 30 min Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 1, 1 hr Post-dose, n=7,7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 15 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 2 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, SA, Dose 1, 1 hr Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 5 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 15 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Severe A, FA, Dose 2, 1 hr Post-dose, n=15, 14 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 30 min Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Moderate A, SA, Dose 2, 1 hr Post-dose, n=7, 7 | 0 Participants |
| GSK2339345 1000 Microgram (mcg) | Number of Participants With Perception of Change in Oropharyngeal Sensation at the Indicated Time Points in Part A | Mild A, SA, Dose 2, 1 hr Post-dose, n=7, 7 | 0 Participants |
Secondary
Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A)
Plasma concentrations of GSK2339345 following the first dose and second dose at each visit in Part A was measured. Samples were collected at the following time points: pre-dose, 2 min, 5 min, 10 min, 30 min, 1 hr and 2 hr (only after Dose 1) after each dose administration at Visits 1, 2 and 3. All non-quantifiable (NQ) values after the pre-first dose value imputed to half lower limit of quantification (LLQ) (LLQ=0.2 nanogram per milliliter \[ng/mL\]). Different participants may have been analyzed for different parameters, so the overall number of par. analyzed reflects everyone in the pharmacokinetic population.
Time frame: From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks)
Population: The Pharmacokinetic (PK) Population comprised of participants in the All Subjects Population for whom a pharmacokinetic sample was obtained and analysed. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 1, Pre-dose, n=14 | 0.000 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 1, 2 min Post-dose, n=14 | 1.3985 nanogram per milliliter (ng/mL) | Full Range 1.4881 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 1, 5 min Post-dose, n=14 | 0.9565 nanogram per milliliter (ng/mL) | Full Range 0.9955 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 1, 10 min Post-dose, n=14 | 0.6925 nanogram per milliliter (ng/mL) | Full Range 0.5075 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 1, 30 min Post-dose, n=14 | 0.2820 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 1, 1 hr Post-dose, n=13 | 0.2950 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 1, 2 hr Post-dose, n=13 | 0.2010 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 2, 2 min Post-dose, n=14 | 1.8735 nanogram per milliliter (ng/mL) | Full Range 3.4305 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 2, 5 min Post-dose, n=14 | 1.4315 nanogram per milliliter (ng/mL) | Full Range 2.3894 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 2, 10 min Post-dose, n=14 | 1.0740 nanogram per milliliter (ng/mL) | Full Range 0.9082 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 2, 30 min Post-dose, n=13 | 0.5230 nanogram per milliliter (ng/mL) | Full Range 0.4645 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 2, Pre-dose, n=14 | 0.1000 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | FA, Dose 2, 1 hr Post-dose, n=14 | 0.5475 nanogram per milliliter (ng/mL) | Full Range 0.2788 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 1, Pre-dose, n=7 | 0.0000 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 1, 2 min Post-dose, n=7 | 1.5010 nanogram per milliliter (ng/mL) | Full Range 1.6036 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 1, 5 min Post-dose, n=7 | 1.5680 nanogram per milliliter (ng/mL) | Full Range 1.0466 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 1, 10 min Post-dose, n=7 | 0.7790 nanogram per milliliter (ng/mL) | Full Range 0.5366 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 1, 30 min Post-dose, n=7 | 0.2470 nanogram per milliliter (ng/mL) | Full Range 3.1688 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 1, 1 hr Post-dose, n=7 | 0.2900 nanogram per milliliter (ng/mL) | Full Range 0.1135 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 1, 2 hr Post-dose, n=7 | 0.1000 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 2, Pre-dose, n=7 | 0.1000 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 2, 2 min Post-dose, n=7 | 1.8280 nanogram per milliliter (ng/mL) | Full Range 3.0811 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 2, 5 min Post-dose, n=7 | 1.4750 nanogram per milliliter (ng/mL) | Full Range 1.7052 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 2, 10 min Post-dose, n=7 | 0.9030 nanogram per milliliter (ng/mL) | Full Range 0.8469 |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 2, 30 min Post-dose, n=7 | 0.4260 nanogram per milliliter (ng/mL) | — |
| Placebo | Plasma Concentrations of GSK2339345 at the Indicated Time Points at Visits 1, 2 and 3 (Part A) | SA, Dose 2, 1 hr Post-dose, n=7 | 0.4290 nanogram per milliliter (ng/mL) | Full Range 0.464 |
Secondary
Time to Reach the Observed Maximum Concentration (Tmax) of GSK2339345 Following Two Repeated Doses
Tmax is defined as the time to reach the observed maximum GSK2339345concentration following two repeated doses at each visit in Part A. Samples were collected at the following time points: pre-dose; 2 min, 5 min, 10 min, 30 min, 1 hr and 2hr (only after Dose 1) post every dose administered at Visits 1, 2 and 3. FA is the first of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A. SA is the second of the two doses of GSK2339345 or placebo administered at any of the three visits in Part A.
Time frame: From 0-4 hr post each dose administered at Visits 1, 2 and 3 in Part A (up to 3 weeks)
Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different time points, so the overall number of participants analyzed reflects everyone in the PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Reach the Observed Maximum Concentration (Tmax) of GSK2339345 Following Two Repeated Doses | FA, Dose 1, n=11 | 0.03333 Hours |
| Placebo | Time to Reach the Observed Maximum Concentration (Tmax) of GSK2339345 Following Two Repeated Doses | FA, Dose 2, n=14 | 0.03333 Hours |
| Placebo | Time to Reach the Observed Maximum Concentration (Tmax) of GSK2339345 Following Two Repeated Doses | SA, Dose 1, n=5 | 0.06667 Hours |
| Placebo | Time to Reach the Observed Maximum Concentration (Tmax) of GSK2339345 Following Two Repeated Doses | SA, Dose 2, n=5 | 0.03333 Hours |
Secondary
Total Cough Count Excluding Transient Coughs Over 4 Hours at Visits 1, 2 and 3 (Part A)
Total cough count (8 hr of recording) was conducted at Visits 1, 2 and 3 (4-hrs of post-dose recording for each of the two doses administered). Coughs were counted by a cough monitor fitted to the participants for 8 hr post Dose 1. Total count excluding transient cough over 4-hrs was done by using the sum of first 4-hrs starting from the time of first dose and the second 4-hrs starting at the time of the second dose respectively. Number of coughs excluding transient cough in 0-4 hr and 4-8 hr period was log-e transformed and used for the analysis. Values were imputed pro-rata if 4-hr epoch was less than 4-hrs. Mean of the total cough counts over 4-hrs recorded post dose of every treatment i.e. placebo or GSK2339345 1000 mcg was reported.
Time frame: Up to 8 hours post-dose at Visits 1, 2 and 3 (Part A)
Population: All Subjects Population. Only participants with at least one 4 hr cough count were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Total Cough Count Excluding Transient Coughs Over 4 Hours at Visits 1, 2 and 3 (Part A) | 0-4 Hr | 70.2 Cough count | Standard Error 0.27 |
| Placebo | Total Cough Count Excluding Transient Coughs Over 4 Hours at Visits 1, 2 and 3 (Part A) | 4-8 Hr | 64.6 Cough count | Standard Error 0.25 |
| GSK2339345 1000 Microgram (mcg) | Total Cough Count Excluding Transient Coughs Over 4 Hours at Visits 1, 2 and 3 (Part A) | 0-4 Hr | 68.3 Cough count | Standard Error 0.27 |
| GSK2339345 1000 Microgram (mcg) | Total Cough Count Excluding Transient Coughs Over 4 Hours at Visits 1, 2 and 3 (Part A) | 4-8 Hr | 67.0 Cough count | Standard Error 0.25 |
90% CI: [0.67, 1.4]
90% CI: [0.79, 1.36]Ratio of adjusted geometric mean