Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
PI3Kd, Pharmacodynamics, dry powder inhaler, GSK2269557, safety, COPD subjects
Brief summary
This is a randomised, double-blind, placebo controlled, parallel group study to evaluate the safety, tolerability, pharmacokinetics and dose response of multiple doses of GSK2269557 administered as a dry powder in COPD subjects. Pharmacodynamic effects on biomarkers will also be assessed. This study will have two parts. In Part A, subjects will be randomized to active or placebo treatment in a 3:1 ratio and in Part B, to placebo or one of the six doses of active treatment in an equal ratio. A sufficient number of COPD subjects (male and female of non-child bearing potential) will be screened to ensure that approximately 30 subjects are enrolled and at least 20 evaluable subjects are obtained for Part A and approximately 35 subjects will be enrolled for Part B. In both the parts, subjects will receive study treatment once daily for 14 consecutive days. Placebo control will be included for a valid evaluation of adverse events attributable to treatment versus those independent of treatment.
Interventions
DRUGGSK2269557 100 MCG
100 mcg of GSK2269557 blended with lactose per blister administered using a dry powder inhaler device
DRUGGSK2269557 500 MCG
500 mcg of GSK2269557 blended with lactose per blister administered using a dry powder inhaler device
DRUGPLACEBO
Lactose administered using a matching dry powder inhaler device
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* The subject has a confirmed and established diagnosis of COPD, as defined by the Global Initiative for Chronic Obstructive lung Disease (GOLD) guidelines. * Male or female of non-child bearing potential between 40 and 75 years of age inclusive, at the time of signing the informed consent. * The subject has a post-bronchodilator \[400 microgram (mcg) salbutamol\] Maximal amount of air FEV1/FVC \<0.7 and FEV1 \>=40% to \<=80% of predicted (Predictions should be according to the European Community of Coal and Steel (ECCS) equations). * Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (pack years = (cigarettes per day smoked/20) x number of years smoked)). * The subject is able to produce \>100 milligram (mg) of sputum at screening. * Body weight \>=45 kilogram (kg) and body mass index (BMI) within the range 17 - 32 kg/square meter (m\^2) (inclusive). * A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy, salpingo-oophrectomy or oophrectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 milli-International units (MIU)/millilitre (mL) and estradiol \< 40 picogram (pg)/mL (\<147 picomole(pmol)/Liter \[L\]) is confirmatory\]. \[Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods, if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.\]; 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. * Based on averaged QTcF values of triplicate ECGs obtained over a brief recording period (e.g. 5 minutes): QTcF \<450 millisecond (msec); or QTcF\<480 msec in subjects with right bundle branch block. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included if the investigator \[in consultation with the Glaxosmithkline (GSK) medical monitor if required\] documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | From the start of study treatment until follow-up (assessed for approximately 19 days) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs. |
| Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 h post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Hematocrit at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | Day 1, Day 7, and Day 14 | Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes \[min\] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). Potential clinical concern range for SBP was \<85 millimeters of mercury (mmHg) (low) and \>160 mmHg (high), for DBP \<45 mmHg (low) and \>100 mmHg (high) and for HR \<40 bpm and \>110 bpm. All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Day 1, Day 7, and Day 14 | Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Clinical significance was judged by the investigator. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 1 (1 h post-dose), Day 7 (pre-dose and 1 h post-dose), and Day 14 (24 h post-dose) | Baseline is Day 1 pre-dose. FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded. Baseline was the maximum of the planned pre-dose measurements on Day 1. Change from Baseline at any post-dose time point was calculated as the post-dose value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | Day 7 (pre-dose) and Day 14 (24 h post-dose) | This outcome measure was used to estimate the inhibition levels of various doses of GSK2269557 by analyzing inflammatory cytokines IL6, IL8, and TNF alpha using Bayesian methods of statistical analysis, using non-informative prior distributions for all modeling parameters. Posterior medians (adjusted median response) and 95% credible intervals are reported here as medians and 95% confidence intervals respectively. 95% credible interval is reported as 2-sided 95% confidence in the statistical analyses. Day 7 assessments could be conducted on Day 7 or Day 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Day 1 (Pre-dose, 5 min, 30 min, 1, 2, 4 & 6 hours post-dose) | A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Only those participants who were available at the indicated time points were analyzed (represented by n=X in the category titles). A value of NA indicates that the geometric mean or 95% confidence interval is not available. |
| Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Day 1, Day 7, and Day 14 | Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | Screening (up to 30 days prior to Day 1) and Follow-up (approximately Day 19) | FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded. |
| Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | Day 1, Day 7, and Day 14 | Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes \[min\] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, and 6 h post-dose on Day 1 | A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Concentration measurements were log-transformed. Only those participants who were available at the indicated time points were analyzed (represented by n=X,X in the category titles). A value of NA indicates that the geometric mean or 95% confidence interval is not available. |
| Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | Day 7 immediately after dosing | Blood samples were collected to determine the plasma concentrations of GSK2269577 immediately after dosing on Day 7. Day 7 sampling could be done on Day 7 or Day 8. |
| Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | Day 7 immediately after dosing | Blood samples were collected to determine the plasma concentrations of GSK2269577 immediately after dosing on Day 7. Concentration values were log-transformed. Day 7 sampling could be done on Day 7 or Day 8. |
| Part A: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7 and Day 15 | Blood samples were collected to determine the (trough) plasma concentration of GSK2269577 on Day 7 (pre-dose) and Day 15 (24 hours after dosing on Day 14). Day 7 assessments could be done either on Day 7 or on Day 8. |
| Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7 and Day 15 | Blood samples were collected to determine the (trough) plasma concentration of GSK2269577 on Day 7 (pre-dose) and Day 15 (24 hours after dosing on Day 14). Day 7 assessments could be done either on Day 7 or on Day 8. |
| Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period | Day 1 to Day 15 | Rescue medication was identified from concomitant medication records and the patient diaries which were provided to the participants to record data throughout the treatment period. Only participants who used rescue medication were analyzed. The value NA indicates that the standard deviation could not be calculated as only one participant was analyzed. |
| Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | From the start of study treatment until follow-up (assessed for approximately 19 days) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs. |
| Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
| Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose) | Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8. |
Countries
Germany
Participant flow
Pre-assignment details
This study was comprised of two parts. In Part A, participants were randomized to active or placebo treatment in a 3:1 ratio and in Part B, to placebo or one of the six doses of active treatment in an equal ratio. Each part comprised a separate sample of participants.
Participants by arm
| Arm | Count |
|---|---|
| Part A: Placebo Participants received 2 inhalations of matching placebo once daily for 14 consecutive days. | 7 |
| Part A: GSK2269577 1000 µg Participants received repeat doses of GSK2269557 1000 micrograms (µg) (2 inhalations of 500 µg each from a single device) administered as a dry powder inhalation, once daily for 14 consecutive days. | 21 |
| Part B: Placebo Participants received four inhalations of matching placebo (from four inhalation devices) once daily for 14 consecutive days. | 5 |
| Part B: GSK2269577 100 µg Participants received repeat doses of GSK2269557 100 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo. | 5 |
| Part B: GSK2269577 200 µg Participants received repeat doses of GSK2269557 200 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 100 µg or placebo. | 5 |
| Part B: GSK2269577 500 µg Participants received repeat doses of GSK2269557 500 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo. | 5 |
| Part B: GSK2269577 700 µg Participants received repeat doses of GSK2269557 700 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 100 µg, 500 µg, or placebo. | 6 |
| Part B: GSK2269577 1000 µg Participants received repeat doses of GSK2269557 1000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing either GSK2269557 500 µg or placebo. | 5 |
| Part B: GSK2269577 2000 µg Participants received repeat doses of GSK2269557 2000 µg administered as a dry powder inhalation, once daily for 14 consecutive days. To maintain blinding, the total dose was delivered through four inhalation devices, each device containing GSK2269557 500 µg. | 5 |
| Total | 64 |
Baseline characteristics
| Characteristic | Part A: Placebo | Part A: GSK2269577 1000 µg | Total | Part B: Placebo | Part B: GSK2269577 100 µg | Part B: GSK2269577 200 µg | Part B: GSK2269577 500 µg | Part B: GSK2269577 700 µg | Part B: GSK2269577 1000 µg | Part B: GSK2269577 2000 µg |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 5.81 | 60.5 Years STANDARD_DEVIATION 6.68 | 63.3 Years STANDARD_DEVIATION 6.34 | 64.4 Years STANDARD_DEVIATION 4.45 | 61.6 Years STANDARD_DEVIATION 4.56 | 62.2 Years STANDARD_DEVIATION 8.23 | 65.4 Years STANDARD_DEVIATION 5.81 | 64.7 Years STANDARD_DEVIATION 7.26 | 62.4 Years STANDARD_DEVIATION 9.24 | 62.4 Years STANDARD_DEVIATION 6.43 |
| Race/Ethnicity, Customized White-White/Caucasian/European Heritage | 7 Participants | 21 Participants | 64 Participants | 5 Participants | 5 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 24 Participants | 2 Participants | 4 Participants | 1 Participants | 0 Participants | 3 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 6 Participants | 14 Participants | 40 Participants | 3 Participants | 1 Participants | 4 Participants | 5 Participants | 3 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 21 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 2 / 7 | 7 / 21 | 3 / 5 | 3 / 5 | 2 / 5 | 1 / 5 | 3 / 6 | 4 / 5 | 2 / 5 |
| serious Total, serious adverse events | 0 / 7 | 1 / 21 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 5 |
Outcome results
Primary
Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | 2.46 International Units per Liter (IU/L) | Standard Deviation 2.585 |
| Part A: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | 1.51 International Units per Liter (IU/L) | Standard Deviation 2.667 |
| Part A: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | -0.64 International Units per Liter (IU/L) | Standard Deviation 6.937 |
| Part A: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | -2.23 International Units per Liter (IU/L) | Standard Deviation 6.522 |
| Part A: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | 3.14 International Units per Liter (IU/L) | Standard Deviation 7.674 |
| Part A: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | 1.83 International Units per Liter (IU/L) | Standard Deviation 4.75 |
| Part A: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | -0.91 International Units per Liter (IU/L) | Standard Deviation 2.203 |
| Part A: Placebo | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | -1.96 International Units per Liter (IU/L) | Standard Deviation 2.873 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | -0.46 International Units per Liter (IU/L) | Standard Deviation 4.187 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | -0.61 International Units per Liter (IU/L) | Standard Deviation 2.208 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | -1.03 International Units per Liter (IU/L) | Standard Deviation 3.081 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | -0.40 International Units per Liter (IU/L) | Standard Deviation 4.117 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | 0.11 International Units per Liter (IU/L) | Standard Deviation 2.55 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | 1.14 International Units per Liter (IU/L) | Standard Deviation 8.586 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | -0.71 International Units per Liter (IU/L) | Standard Deviation 2.592 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | -0.21 International Units per Liter (IU/L) | Standard Deviation 9.785 |
Primary
Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | 0.56 g/L | Standard Deviation 2.23 |
| Part A: Placebo | Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post doseTotal protein; Day | 0.53 g/L | Standard Deviation 2.379 |
| Part A: Placebo | Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | 0.56 g/L | Standard Deviation 3.619 |
| Part A: Placebo | Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | 0.84 g/L | Standard Deviation 3.887 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | 1.15 g/L | Standard Deviation 2.606 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | 0.80 g/L | Standard Deviation 1.576 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | 1.28 g/L | Standard Deviation 2.599 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post doseTotal protein; Day | 0.52 g/L | Standard Deviation 2.004 |
Primary
Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | 0.033 Millimoles per Liter (mmol/L) | Standard Deviation 0.0535 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | 0.033 Millimoles per Liter (mmol/L) | Standard Deviation 0.085 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | -0.053 Millimoles per Liter (mmol/L) | Standard Deviation 0.3333 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | 0.161 Millimoles per Liter (mmol/L) | Standard Deviation 0.2659 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | 0.103 Millimoles per Liter (mmol/L) | Standard Deviation 0.2279 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | 0.161 Millimoles per Liter (mmol/L) | Standard Deviation 0.2562 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | 1.21 Millimoles per Liter (mmol/L) | Standard Deviation 2.8 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | 0.81 Millimoles per Liter (mmol/L) | Standard Deviation 1.297 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | BUN; Day 7/Day 8, pre-dose | -0.530 Millimoles per Liter (mmol/L) | Standard Deviation 1.083 |
| Part A: Placebo | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | BUN; Day 14, 24 h post dose | -0.464 Millimoles per Liter (mmol/L) | Standard Deviation 1.1979 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | 0.83 Millimoles per Liter (mmol/L) | Standard Deviation 1.39 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | 0.033 Millimoles per Liter (mmol/L) | Standard Deviation 0.0617 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | 0.065 Millimoles per Liter (mmol/L) | Standard Deviation 0.3347 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | 0.029 Millimoles per Liter (mmol/L) | Standard Deviation 0.0588 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | BUN; Day 14, 24 h post dose | 0.111 Millimoles per Liter (mmol/L) | Standard Deviation 1.2147 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | 0.012 Millimoles per Liter (mmol/L) | Standard Deviation 0.2888 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | 0.88 Millimoles per Liter (mmol/L) | Standard Deviation 1.56 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | 0.024 Millimoles per Liter (mmol/L) | Standard Deviation 0.4914 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | BUN; Day 7/Day 8, pre-dose | -0.192 Millimoles per Liter (mmol/L) | Standard Deviation 0.8124 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | 0.011 Millimoles per Liter (mmol/L) | Standard Deviation 0.3539 |
Primary
Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBCs; Day 7/Day 8, pre-dose | 0.023 10^12 cells/Liter (TI/L) | Standard Deviation 0.23 |
| Part A: Placebo | Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBCs; Day 14, 24 h post dose | 0.119 10^12 cells/Liter (TI/L) | Standard Deviation 0.201 |
| Part A: Placebo | Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | 0.005 10^12 cells/Liter (TI/L) | Standard Deviation 0.014 |
| Part A: Placebo | Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | 0.009 10^12 cells/Liter (TI/L) | Standard Deviation 0.014 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | 0.003 10^12 cells/Liter (TI/L) | Standard Deviation 0.01 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBCs; Day 7/Day 8, pre-dose | 0.060 10^12 cells/Liter (TI/L) | Standard Deviation 0.141 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | 0.003 10^12 cells/Liter (TI/L) | Standard Deviation 0.009 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBCs; Day 14, 24 h post dose | 0.063 10^12 cells/Liter (TI/L) | Standard Deviation 0.16 |
Primary
Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | -0.736 10^9 cells per liter (GI/L) | Standard Deviation 0.937 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | WBC; Day 14, 24 h post dose | -0.140 10^9 cells per liter (GI/L) | Standard Deviation 1.22 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | -0.664 10^9 cells per liter (GI/L) | Standard Deviation 0.624 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | -0.153 10^9 cells per liter (GI/L) | Standard Deviation 0.887 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | -0.033 10^9 cells per liter (GI/L) | Standard Deviation 0.321 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | -0.049 10^9 cells per liter (GI/L) | Standard Deviation 0.197 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | -0.036 10^9 cells per liter (GI/L) | Standard Deviation 0.074 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | 0.039 10^9 cells per liter (GI/L) | Standard Deviation 0.178 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | -0.006 10^9 cells per liter (GI/L) | Standard Deviation 0.051 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | 0.001 10^9 cells per liter (GI/L) | Standard Deviation 0.085 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | -0.001 10^9 cells per liter (GI/L) | Standard Deviation 0.006 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Basophils; Day 14, 24 h post dose | -0.003 10^9 cells per liter (GI/L) | Standard Deviation 0.013 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | 1.6 10^9 cells per liter (GI/L) | Standard Deviation 20.58 |
| Part A: Placebo | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Platelets; Day 14, 24 h post dose | 14.7 10^9 cells per liter (GI/L) | Standard Deviation 21.8 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | 0.006 10^9 cells per liter (GI/L) | Standard Deviation 0.015 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | -0.080 10^9 cells per liter (GI/L) | Standard Deviation 1.387 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | -0.022 10^9 cells per liter (GI/L) | Standard Deviation 0.116 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | WBC; Day 14, 24 h post dose | -0.510 10^9 cells per liter (GI/L) | Standard Deviation 0.947 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | 17.9 10^9 cells per liter (GI/L) | Standard Deviation 36.44 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | -0.363 10^9 cells per liter (GI/L) | Standard Deviation 1.342 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | 0.032 10^9 cells per liter (GI/L) | Standard Deviation 0.074 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | -0.547 10^9 cells per liter (GI/L) | Standard Deviation 0.977 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Basophils; Day 14, 24 h post dose | 0.002 10^9 cells per liter (GI/L) | Standard Deviation 0.018 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | 0.172 10^9 cells per liter (GI/L) | Standard Deviation 0.597 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | 0.010 10^9 cells per liter (GI/L) | Standard Deviation 0.075 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | 0.030 10^9 cells per liter (GI/L) | Standard Deviation 0.245 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Platelets; Day 14, 24 h post dose | 23.5 10^9 cells per liter (GI/L) | Standard Deviation 37.43 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Counts of White Blood Cells (WBC), Total Neutrophils (Total Absolute Neutrophil Count [ANC]), Lymphocytes, Monocytes, Eosinophils, Basophils, and Platelets at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | 0.046 10^9 cells per liter (GI/L) | Standard Deviation 0.149 |
Primary
Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | 2.31 Micromoles/Liter (micromol/L) | Standard Deviation 4.385 |
| Part A: Placebo | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | 3.64 Micromoles/Liter (micromol/L) | Standard Deviation 6.035 |
| Part A: Placebo | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | 0.33 Micromoles/Liter (micromol/L) | Standard Deviation 0.419 |
| Part A: Placebo | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | 0.27 Micromoles/Liter (micromol/L) | Standard Deviation 0.496 |
| Part A: Placebo | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | 1.23 Micromoles/Liter (micromol/L) | Standard Deviation 2.447 |
| Part A: Placebo | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | 0.90 Micromoles/Liter (micromol/L) | Standard Deviation 2.805 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | 0.02 Micromoles/Liter (micromol/L) | Standard Deviation 2.59 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | -0.62 Micromoles/Liter (micromol/L) | Standard Deviation 5.104 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | 0.10 Micromoles/Liter (micromol/L) | Standard Deviation 0.329 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | 0.07 Micromoles/Liter (micromol/L) | Standard Deviation 3.259 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | 0.78 Micromoles/Liter (micromol/L) | Standard Deviation 1.72 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | 0.04 Micromoles/Liter (micromol/L) | Standard Deviation 0.398 |
Primary
Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points
Baseline is Day 1 pre-dose. FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded. Baseline was the maximum of the planned pre-dose measurements on Day 1. Change from Baseline at any post-dose time point was calculated as the post-dose value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 1 (1 h post-dose), Day 7 (pre-dose and 1 h post-dose), and Day 14 (24 h post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FEV1, Day 7/8, Pre-dose | 0.03 Liters |
| Part A: Placebo | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FVC, Day 1, 1 h post dose | 0.17 Liters |
| Part A: Placebo | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FEV1, Day 14, 24 h post dose | -0.01 Liters |
| Part A: Placebo | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FVC, Day 7/8, Predose | 0.02 Liters |
| Part A: Placebo | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FEV1, Day 7/8, 1 h post dose | 0.27 Liters |
| Part A: Placebo | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FVC, Day 7/8, 1 h post dose | 0.33 Liters |
| Part A: Placebo | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FVC, Day 14, 24 h post dose | -0.04 Liters |
| Part A: Placebo | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FEV1, Day 1, 1 h post dose | 0.15 Liters |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FVC, Day 14, 24 h post dose | 0.10 Liters |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FEV1, Day 1, 1 h post dose | 0.10 Liters |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FEV1, Day 7/8, Pre-dose | -0.04 Liters |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FEV1, Day 7/8, 1 h post dose | 0.18 Liters |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FEV1, Day 14, 24 h post dose | 0.01 Liters |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FVC, Day 7/8, 1 h post dose | 0.22 Liters |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FVC, Day 1, 1 h post dose | 0.16 Liters |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at the Indicated Time Points | FVC, Day 7/8, Predose | 0.00 Liters |
Primary
Part A: Change From Baseline in Hematocrit at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit; Day 7/Day 8, pre-dose | 0.003 Ratio | Standard Deviation 0.023 |
| Part A: Placebo | Part A: Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit; Day 14, 24 h post dose | 0.011 Ratio | Standard Deviation 0.019 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit; Day 7/Day 8, pre-dose | 0.007 Ratio | Standard Deviation 0.013 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Hematocrit at the Indicated Time Points | Hematocrit; Day 14, 24 h post dose | 0.006 Ratio | Standard Deviation 0.016 |
Primary
Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 h post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | -1.3 Grams/Liter (g/L) | Standard Deviation 6.63 |
| Part A: Placebo | Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | 0.3 Grams/Liter (g/L) | Standard Deviation 6.97 |
| Part A: Placebo | Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | -5.3 Grams/Liter (g/L) | Standard Deviation 7.32 |
| Part A: Placebo | Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | -8.4 Grams/Liter (g/L) | Standard Deviation 4.39 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | -2.4 Grams/Liter (g/L) | Standard Deviation 6.45 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | 1.6 Grams/Liter (g/L) | Standard Deviation 4.17 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | -2.2 Grams/Liter (g/L) | Standard Deviation 4.54 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | 1.0 Grams/Liter (g/L) | Standard Deviation 4.12 |
Primary
Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | MCH; Day 7/Day 8, pre-dose | -0.46 Picograms (pg) | Standard Deviation 0.602 |
| Part A: Placebo | Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | MCH; Day 14, 24 h post dose | -0.76 Picograms (pg) | Standard Deviation 0.586 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | MCH; Day 7/Day 8, pre-dose | -0.06 Picograms (pg) | Standard Deviation 0.44 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | MCH; Day 14, 24 h post dose | -0.23 Picograms (pg) | Standard Deviation 0.593 |
Primary
Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Baseline is Day 1 pre-dose. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | 0.11 Femtoliters (fL) | Standard Deviation 0.687 |
| Part A: Placebo | Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | 0.07 Femtoliters (fL) | Standard Deviation 0.848 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | 0.43 Femtoliters (fL) | Standard Deviation 0.697 |
| Part A: GSK2269577 1000 µg | Part A: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | -0.03 Femtoliters (fL) | Standard Deviation 1.193 |
Primary
Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline
Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes \[min\] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). Potential clinical concern range for SBP was \<85 millimeters of mercury (mmHg) (low) and \>160 mmHg (high), for DBP \<45 mmHg (low) and \>100 mmHg (high) and for HR \<40 bpm and \>110 bpm. All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Day 1, Day 7, and Day 14
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 1 Participants |
| Part A: Placebo | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part A: Placebo | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
| Part A: Placebo | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 1 Participants |
| Part A: Placebo | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 0 Participants |
| Part A: Placebo | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 1 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 1 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 0 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
Primary
Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time frame: From the start of study treatment until follow-up (assessed for approximately 19 days)
Population: Safety Population: all participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 2 Participants |
| Part A: Placebo | Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 0 Participants |
| Part A: Placebo | Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 2 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 9 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 1 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 6 Participants |
Primary
Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline
Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Clinical significance was judged by the investigator. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Day 1, Day 7, and Day 14
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 2 Participants |
| Part A: Placebo | Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 5 Participants |
| Part A: Placebo | Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 13 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 8 Participants |
| Part A: GSK2269577 1000 µg | Part A: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
Primary
Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14
This outcome measure was used to estimate the inhibition levels of various doses of GSK2269557 by analyzing inflammatory cytokines IL6, IL8, and TNF alpha using Bayesian methods of statistical analysis, using non-informative prior distributions for all modeling parameters. Posterior medians (adjusted median response) and 95% credible intervals are reported here as medians and 95% confidence intervals respectively. 95% credible interval is reported as 2-sided 95% confidence in the statistical analyses. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Day 7 (pre-dose) and Day 14 (24 h post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Placebo | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 14 | 2.91 Picograms/milliliter (pg/mL) |
| Part A: Placebo | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 14 | 35.15 Picograms/milliliter (pg/mL) |
| Part A: Placebo | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 14 | 2942.28 Picograms/milliliter (pg/mL) |
| Part A: Placebo | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 7/Day 8 | 41.30 Picograms/milliliter (pg/mL) |
| Part A: Placebo | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 7/Day 8 | 2633.21 Picograms/milliliter (pg/mL) |
| Part A: Placebo | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 7/Day 8 | 3.35 Picograms/milliliter (pg/mL) |
| Part A: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 7/Day 8 | 37.40 Picograms/milliliter (pg/mL) |
| Part A: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 14 | 2664.75 Picograms/milliliter (pg/mL) |
| Part A: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 14 | 3.02 Picograms/milliliter (pg/mL) |
| Part A: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 14 | 37.60 Picograms/milliliter (pg/mL) |
| Part A: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 7/Day 8 | 1.55 Picograms/milliliter (pg/mL) |
| Part A: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 7/Day 8 | 2118.15 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 200 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 7/Day 8 | 1.16 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 200 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 7/Day 8 | 1860.78 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 200 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 14 | 1.25 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 200 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 14 | 1879.92 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 200 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 7/Day 8 | 28.23 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 200 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 14 | 28.27 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 500 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 7/Day 8 | 1.54 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 500 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 7/Day 8 | 30.82 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 500 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 14 | 22.68 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 500 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 7/Day 8 | 1523.63 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 500 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 14 | 1619.12 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 500 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 14 | 1.26 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 700 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 14 | 1356.35 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 700 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 14 | 35.19 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 700 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 7/Day 8 | 7.32 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 700 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 14 | 3.99 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 700 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 7/Day 8 | 2650.13 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 700 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 7/Day 8 | 52.23 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 7/Day 8 | 2636.08 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 14 | 2394.65 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 14 | 42.56 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 7/Day 8 | 3.68 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 7/Day 8 | 31.25 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 1000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 14 | 3.00 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 2000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 7/Day 8 | 2279.48 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 2000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 14 | 41.52 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 2000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 14 | 1.53 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 2000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL8, Day 14 | 2170.41 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 2000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | TNFalpha, Day 7/Day 8 | 2.62 Picograms/milliliter (pg/mL) |
| Part B: GSK2269577 2000 µg | Part B: Adjusted Median Response of Cytokine (Interleukin 6 [IL6], Interleukin 8 [IL8], Tumor Necrosis Factor Alpha [TNFalpha]) Concentrations in Induced Sputum, on Day 7 and Day 14 | IL6, Day 7/Day 8 | 33.40 Picograms/milliliter (pg/mL) |
p-value: 0.59995% CI: [0.39, 2.07]Bayesian repeated measures
p-value: 0.44295% CI: [0.43, 2.59]Bayesian repeated measures
p-value: 0.82395% CI: [0.3, 1.57]Bayesian repeated measures
p-value: 0.6995% CI: [0.33, 1.97]Bayesian repeated measures
p-value: 0.76495% CI: [0.33, 1.71]Bayesian repeated measures
p-value: 0.84195% CI: [0.27, 1.56]Bayesian repeated measures
p-value: 0.70295% CI: [0.35, 1.81]Bayesian repeated measures
p-value: 0.57895% CI: [0.33, 2.47]Bayesian repeated measures
p-value: 0.78395% CI: [0.29, 1.7]Bayesian repeated measures
p-value: 0.79795% CI: [0.22, 1.87]Bayesian repeated measures
p-value: 0.91995% CI: [0.27, 1.26]Bayesian repeated measures
p-value: 0.89295% CI: [0.21, 1.43]Bayesian repeated measures
p-value: 0.8695% CI: [0.11, 1.93]Bayesian repeated measures
p-value: 0.46395% CI: [0.38, 2.86]Bayesian repeated measures
p-value: 0.93295% CI: [0.09, 1.42]Bayesian repeated measures
p-value: 0.95295% CI: [0.16, 1.17]Bayesian repeated measures
p-value: 0.87395% CI: [0.12, 1.81]Bayesian repeated measures
p-value: 0.95395% CI: [0.16, 1.16]Bayesian repeated measures
p-value: 0.28195% CI: [0.56, 2.82]Bayesian repeated measures
p-value: 0.595% CI: [0.42, 2.35]Bayesian repeated measures
p-value: 0.74495% CI: [0.32, 1.77]Bayesian repeated measures
p-value: 0.33495% CI: [0.49, 3.04]Bayesian repeated measures
p-value: 0.69895% CI: [0.35, 1.85]Bayesian repeated measures
p-value: 0.35395% CI: [0.48, 2.88]Bayesian repeated measures
p-value: 0.48995% CI: [0.45, 2.26]Bayesian repeated measures
p-value: 0.9495% CI: [0.17, 1.23]Bayesian repeated measures
p-value: 0.49595% CI: [0.42, 2.4]Bayesian repeated measures
p-value: 0.64795% CI: [0.28, 2.37]Bayesian repeated measures
p-value: 0.64695% CI: [0.4, 1.86]Bayesian repeated measures
p-value: 0.74195% CI: [0.29, 1.9]Bayesian repeated measures
p-value: 0.10995% CI: [0.62, 7.95]Bayesian repeated measures
p-value: 0.2495% CI: [0.55, 3.45]Bayesian repeated measures
p-value: 0.44795% CI: [0.27, 4.44]Bayesian repeated measures
p-value: 0.47295% CI: [0.39, 2.74]Bayesian repeated measures
p-value: 0.69895% CI: [0.21, 2.9]Bayesian repeated measures
p-value: 0.91195% CI: [0.21, 1.37]Bayesian repeated measures
Secondary
Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose
A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Only those participants who were available at the indicated time points were analyzed (represented by n=X in the category titles). A value of NA indicates that the geometric mean or 95% confidence interval is not available.
Time frame: Day 1 (Pre-dose, 5 min, 30 min, 1, 2, 4 & 6 hours post-dose)
Population: PK Population: participants in the Safety Population for whom a PK sample was obtained and analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Placebo | Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Pre-dose; n=0 | NA pg/mL |
| Part A: Placebo | Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 5 min; n=21 | 386.2 pg/mL |
| Part A: Placebo | Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 30 min; n=21 | 337.2 pg/mL |
| Part A: Placebo | Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 1 h; n=21 | 379.1 pg/mL |
| Part A: Placebo | Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 2 h; n=21 | 531.1 pg/mL |
| Part A: Placebo | Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 4 h; n=21 | 419.5 pg/mL |
| Part A: Placebo | Part A: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 6 h; n=21 | 334.4 pg/mL |
Secondary
Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7
Blood samples were collected to determine the plasma concentrations of GSK2269577 immediately after dosing on Day 7. Day 7 sampling could be done on Day 7 or Day 8.
Time frame: Day 7 immediately after dosing
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Placebo | Part A: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | 1109.1 pg/mL |
Secondary
Part A: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15
Blood samples were collected to determine the (trough) plasma concentration of GSK2269577 on Day 7 (pre-dose) and Day 15 (24 hours after dosing on Day 14). Day 7 assessments could be done either on Day 7 or on Day 8.
Time frame: Day 7 and Day 15
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Placebo | Part A: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7/Day 8 | 604.1 pg/mL |
| Part A: Placebo | Part A: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 15 | 711.2 pg/mL |
Secondary
Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | 0.36 International Units per Liter (IU/L) | Standard Deviation 2.268 |
| Part A: Placebo | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | -0.64 International Units per Liter (IU/L) | Standard Deviation 0.934 |
| Part A: Placebo | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | 1.54 International Units per Liter (IU/L) | Standard Deviation 4.503 |
| Part A: Placebo | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | -0.6 International Units per Liter (IU/L) | Standard Deviation 2.119 |
| Part A: Placebo | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | 1.38 International Units per Liter (IU/L) | Standard Deviation 2.464 |
| Part A: Placebo | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | 0.44 International Units per Liter (IU/L) | Standard Deviation 1.691 |
| Part A: Placebo | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | 1.58 International Units per Liter (IU/L) | Standard Deviation 2.24 |
| Part A: Placebo | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | 1.88 International Units per Liter (IU/L) | Standard Deviation 5.45 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | 3.76 International Units per Liter (IU/L) | Standard Deviation 11.142 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | 0.16 International Units per Liter (IU/L) | Standard Deviation 1.673 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | 0.1 International Units per Liter (IU/L) | Standard Deviation 2.625 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | 4.78 International Units per Liter (IU/L) | Standard Deviation 7.294 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | 3.66 International Units per Liter (IU/L) | Standard Deviation 6.057 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | 1.62 International Units per Liter (IU/L) | Standard Deviation 5.756 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | -0.3 International Units per Liter (IU/L) | Standard Deviation 1.856 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | 2.18 International Units per Liter (IU/L) | Standard Deviation 3.17 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | 1.64 International Units per Liter (IU/L) | Standard Deviation 7.946 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | -0.42 International Units per Liter (IU/L) | Standard Deviation 3.13 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | -2.76 International Units per Liter (IU/L) | Standard Deviation 6.176 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | -2.44 International Units per Liter (IU/L) | Standard Deviation 7.23 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | -0.2 International Units per Liter (IU/L) | Standard Deviation 6.109 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | -2.44 International Units per Liter (IU/L) | Standard Deviation 3.443 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | -2.64 International Units per Liter (IU/L) | Standard Deviation 6.532 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | -0.96 International Units per Liter (IU/L) | Standard Deviation 4.556 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | -0.3 International Units per Liter (IU/L) | Standard Deviation 4.471 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | 5.7 International Units per Liter (IU/L) | Standard Deviation 9.986 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | 2.6 International Units per Liter (IU/L) | Standard Deviation 4.994 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | -1.64 International Units per Liter (IU/L) | Standard Deviation 6.027 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | 0.26 International Units per Liter (IU/L) | Standard Deviation 5.185 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | 0.84 International Units per Liter (IU/L) | Standard Deviation 5.223 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | 0.26 International Units per Liter (IU/L) | Standard Deviation 9.829 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | -0.72 International Units per Liter (IU/L) | Standard Deviation 5.485 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | -0.22 International Units per Liter (IU/L) | Standard Deviation 3.672 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | 1.52 International Units per Liter (IU/L) | Standard Deviation 5.783 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | -0.95 International Units per Liter (IU/L) | Standard Deviation 7.807 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | -1.1 International Units per Liter (IU/L) | Standard Deviation 8.535 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | -0.1 International Units per Liter (IU/L) | Standard Deviation 2.994 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | -0.72 International Units per Liter (IU/L) | Standard Deviation 4.63 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | 0.02 International Units per Liter (IU/L) | Standard Deviation 3.129 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | 1.88 International Units per Liter (IU/L) | Standard Deviation 4.747 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | -2.56 International Units per Liter (IU/L) | Standard Deviation 5.607 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | -2.86 International Units per Liter (IU/L) | Standard Deviation 5.478 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | -1.66 International Units per Liter (IU/L) | Standard Deviation 4.536 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | -2.4 International Units per Liter (IU/L) | Standard Deviation 5.036 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | -5.34 International Units per Liter (IU/L) | Standard Deviation 19.016 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | -6.16 International Units per Liter (IU/L) | Standard Deviation 17.113 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | -0.92 International Units per Liter (IU/L) | Standard Deviation 22.572 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | -3.18 International Units per Liter (IU/L) | Standard Deviation 9.7 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 14, 24 h post dose | 1.58 International Units per Liter (IU/L) | Standard Deviation 3.754 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 7/Day 8, pre-dose | 0.74 International Units per Liter (IU/L) | Standard Deviation 1.141 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 7/Day 8, pre-dose | 1.66 International Units per Liter (IU/L) | Standard Deviation 5.465 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | GGT; Day 14, 24 h post dose | 0.54 International Units per Liter (IU/L) | Standard Deviation 1.923 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 14, 24 h post dose | 2.66 International Units per Liter (IU/L) | Standard Deviation 1.25 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALT; Day 7/Day 8, pre-dose | 1.42 International Units per Liter (IU/L) | Standard Deviation 2.791 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | AST; Day 7/Day 8, pre-dose | 3.04 International Units per Liter (IU/L) | Standard Deviation 2.048 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), and Gamma Glutamyl Transferase (GGT) at the Indicated Time Points | ALP; Day 14, 24 h post dose | 5.2 International Units per Liter (IU/L) | Standard Deviation 4.038 |
Secondary
Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | 0.96 g/L | Standard Deviation 1.773 |
| Part A: Placebo | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | 0.96 g/L | Standard Deviation 3.392 |
| Part A: Placebo | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | 1.34 g/L | Standard Deviation 2.46 |
| Part A: Placebo | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post dose | 0.9 g/L | Standard Deviation 2.965 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post dose | 0.7 g/L | Standard Deviation 2.134 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | 0.96 g/L | Standard Deviation 2.393 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | 1.22 g/L | Standard Deviation 1.571 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | 0.72 g/L | Standard Deviation 1.203 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | -0.16 g/L | Standard Deviation 3.737 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post dose | -0.12 g/L | Standard Deviation 2.538 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | 2.22 g/L | Standard Deviation 4.953 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | 0.96 g/L | Standard Deviation 3.012 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post dose | -1.16 g/L | Standard Deviation 2.157 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | 0.88 g/L | Standard Deviation 0.887 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | 0.98 g/L | Standard Deviation 2.039 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | -1.96 g/L | Standard Deviation 3.635 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | -2.13 g/L | Standard Deviation 2.156 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post dose | -1.13 g/L | Standard Deviation 1.365 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | -0.6 g/L | Standard Deviation 1.814 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | -1.4 g/L | Standard Deviation 2.662 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | 1.18 g/L | Standard Deviation 1.069 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | 1.78 g/L | Standard Deviation 2.338 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post dose | 0.44 g/L | Standard Deviation 1.001 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | 0.72 g/L | Standard Deviation 1.154 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 14, 24 h post dose | 0.26 g/L | Standard Deviation 1.187 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Albumin; Day 7/Day 8, pre-dose | 0.3 g/L | Standard Deviation 1.49 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 14, 24 h post dose | 0.7 g/L | Standard Deviation 2.277 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Albumin and Total Protein at the Indicated Time Points | Total protein; Day 7/Day 8, pre-dose | 1.12 g/L | Standard Deviation 1.571 |
Secondary
Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | 0.048 Millimoles per Liter (mmol/L) | Standard Deviation 0.0444 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | -0.086 Millimoles per Liter (mmol/L) | Standard Deviation 0.3743 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | 0.19 Millimoles per Liter (mmol/L) | Standard Deviation 0.1944 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | -0.16 Millimoles per Liter (mmol/L) | Standard Deviation 1.301 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | 0.024 Millimoles per Liter (mmol/L) | Standard Deviation 0.0865 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | 0 Millimoles per Liter (mmol/L) | Standard Deviation 1.206 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | -0.06 Millimoles per Liter (mmol/L) | Standard Deviation 0.2939 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 14, 24 h post dose | -0.232 Millimoles per Liter (mmol/L) | Standard Deviation 0.3592 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | 0.246 Millimoles per Liter (mmol/L) | Standard Deviation 0.3088 |
| Part A: Placebo | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 7/Day 8, pre-dose | 0.314 Millimoles per Liter (mmol/L) | Standard Deviation 0.7077 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | 0.09 Millimoles per Liter (mmol/L) | Standard Deviation 0.2793 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 7/Day 8, pre-dose | -0.504 Millimoles per Liter (mmol/L) | Standard Deviation 0.6955 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | 0.12 Millimoles per Liter (mmol/L) | Standard Deviation 0.4282 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | 0.044 Millimoles per Liter (mmol/L) | Standard Deviation 0.0397 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | -0.04 Millimoles per Liter (mmol/L) | Standard Deviation 3.233 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | -0.142 Millimoles per Liter (mmol/L) | Standard Deviation 0.3746 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | 0.054 Millimoles per Liter (mmol/L) | Standard Deviation 0.4057 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | -0.012 Millimoles per Liter (mmol/L) | Standard Deviation 0.0482 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 14, 24 h post dose | -0.124 Millimoles per Liter (mmol/L) | Standard Deviation 0.7502 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | 0.6 Millimoles per Liter (mmol/L) | Standard Deviation 1.626 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | 0.58 Millimoles per Liter (mmol/L) | Standard Deviation 1.399 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | -0.12 Millimoles per Liter (mmol/L) | Standard Deviation 1.714 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | 0.05 Millimoles per Liter (mmol/L) | Standard Deviation 0.1937 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | 0.05 Millimoles per Liter (mmol/L) | Standard Deviation 0.0696 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | 0.06 Millimoles per Liter (mmol/L) | Standard Deviation 0.0579 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | 0.26 Millimoles per Liter (mmol/L) | Standard Deviation 0.5456 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 14, 24 h post dose | 0.142 Millimoles per Liter (mmol/L) | Standard Deviation 1.0269 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | 0.434 Millimoles per Liter (mmol/L) | Standard Deviation 0.5451 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 7/Day 8, pre-dose | 0.342 Millimoles per Liter (mmol/L) | Standard Deviation 0.8193 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | 0.336 Millimoles per Liter (mmol/L) | Standard Deviation 0.5268 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | 1.18 Millimoles per Liter (mmol/L) | Standard Deviation 1.139 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | -0.43 Millimoles per Liter (mmol/L) | Standard Deviation 1.4084 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | 0.054 Millimoles per Liter (mmol/L) | Standard Deviation 0.2294 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | -0.204 Millimoles per Liter (mmol/L) | Standard Deviation 0.2563 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | -0.128 Millimoles per Liter (mmol/L) | Standard Deviation 0.3241 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | -0.01 Millimoles per Liter (mmol/L) | Standard Deviation 0.0758 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | 0.46 Millimoles per Liter (mmol/L) | Standard Deviation 1.447 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 7/Day 8, pre-dose | -0.91 Millimoles per Liter (mmol/L) | Standard Deviation 1.0653 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 14, 24 h post dose | -0.906 Millimoles per Liter (mmol/L) | Standard Deviation 1.6431 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | 0.01 Millimoles per Liter (mmol/L) | Standard Deviation 0.0648 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 7/Day 8, pre-dose | -0.29 Millimoles per Liter (mmol/L) | Standard Deviation 0.4396 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | -0.18 Millimoles per Liter (mmol/L) | Standard Deviation 2.515 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 14, 24 h post dose | -0.335 Millimoles per Liter (mmol/L) | Standard Deviation 0.2793 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | -0.34 Millimoles per Liter (mmol/L) | Standard Deviation 0.7332 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | 0.013 Millimoles per Liter (mmol/L) | Standard Deviation 0.203 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | -0.008 Millimoles per Liter (mmol/L) | Standard Deviation 0.0655 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | -0.042 Millimoles per Liter (mmol/L) | Standard Deviation 0.0422 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | -0.33 Millimoles per Liter (mmol/L) | Standard Deviation 2.072 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | 0.135 Millimoles per Liter (mmol/L) | Standard Deviation 0.3172 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | -0.11 Millimoles per Liter (mmol/L) | Standard Deviation 0.5658 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | 0.14 Millimoles per Liter (mmol/L) | Standard Deviation 0.1259 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | 1.06 Millimoles per Liter (mmol/L) | Standard Deviation 1.074 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | 0.276 Millimoles per Liter (mmol/L) | Standard Deviation 0.3566 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 7/Day 8, pre-dose | -0.244 Millimoles per Liter (mmol/L) | Standard Deviation 1.2909 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | -0.076 Millimoles per Liter (mmol/L) | Standard Deviation 0.3518 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | 0.03 Millimoles per Liter (mmol/L) | Standard Deviation 0.0292 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 14, 24 h post dose | -0.364 Millimoles per Liter (mmol/L) | Standard Deviation 0.8554 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | 0.11 Millimoles per Liter (mmol/L) | Standard Deviation 0.4369 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | 0.066 Millimoles per Liter (mmol/L) | Standard Deviation 0.0811 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | 0.7 Millimoles per Liter (mmol/L) | Standard Deviation 1.815 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 7/Day 8, pre-dose | -0.246 Millimoles per Liter (mmol/L) | Standard Deviation 0.273 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 14, 24 h post dose | 0.072 Millimoles per Liter (mmol/L) | Standard Deviation 0.5946 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 14, 24 h post dose | 0.036 Millimoles per Liter (mmol/L) | Standard Deviation 0.0568 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Potassium; Day 7/Day 8, pre-dose | 0.192 Millimoles per Liter (mmol/L) | Standard Deviation 0.4587 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 14, 24 h post dose | -0.4 Millimoles per Liter (mmol/L) | Standard Deviation 2.72 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Glucose; Day 14, 24 h post dose | -0.314 Millimoles per Liter (mmol/L) | Standard Deviation 0.3871 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Sodium; Day 7/Day 8, pre-dose | -0.84 Millimoles per Liter (mmol/L) | Standard Deviation 2.137 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 7/Day 8, pre-dose | 0.162 Millimoles per Liter (mmol/L) | Standard Deviation 1.2285 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Calcium; Day 7/Day 8, pre-dose | 0.044 Millimoles per Liter (mmol/L) | Standard Deviation 0.0365 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Calcium, Potassium, Sodium, Glucose, and Blood Urea Nitrogen (BUN) at the Indicated Time Points | Urea/BUN; Day 14, 24 h post dose | 0.186 Millimoles per Liter (mmol/L) | Standard Deviation 2.0478 |
Secondary
Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | 0.242 10^9 cells per liter (GI/L) | Standard Deviation 0.4797 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | -13.8 10^9 cells per liter (GI/L) | Standard Deviation 14.22 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | 0.372 10^9 cells per liter (GI/L) | Standard Deviation 1.5852 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | -0.09 10^9 cells per liter (GI/L) | Standard Deviation 0.4499 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | -0.44 10^9 cells per liter (GI/L) | Standard Deviation 0.4288 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 14, 24 h post dose | -3.3 10^9 cells per liter (GI/L) | Standard Deviation 22.25 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | 0.164 10^9 cells per liter (GI/L) | Standard Deviation 0.9782 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | -0.002 10^9 cells per liter (GI/L) | Standard Deviation 0.0576 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | -0.022 10^9 cells per liter (GI/L) | Standard Deviation 0.0676 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 14, 24 h post dose | -0.49 10^9 cells per liter (GI/L) | Standard Deviation 0.5204 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | 0.046 10^9 cells per liter (GI/L) | Standard Deviation 0.0472 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 14, 24 h post dose | 0.004 10^9 cells per liter (GI/L) | Standard Deviation 0.0167 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | 0.014 10^9 cells per liter (GI/L) | Standard Deviation 0.0241 |
| Part A: Placebo | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | -0.062 10^9 cells per liter (GI/L) | Standard Deviation 0.0867 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | -0.024 10^9 cells per liter (GI/L) | Standard Deviation 1.1519 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | -0.178 10^9 cells per liter (GI/L) | Standard Deviation 0.5657 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | 0.01 10^9 cells per liter (GI/L) | Standard Deviation 0.0485 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | -0.538 10^9 cells per liter (GI/L) | Standard Deviation 1.1027 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | -0.012 10^9 cells per liter (GI/L) | Standard Deviation 0.0926 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | 0.05 10^9 cells per liter (GI/L) | Standard Deviation 0.0941 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 14, 24 h post dose | -13 10^9 cells per liter (GI/L) | Standard Deviation 26.52 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | -0.002 10^9 cells per liter (GI/L) | Standard Deviation 0.0228 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | -0.264 10^9 cells per liter (GI/L) | Standard Deviation 0.3134 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | 0.09 10^9 cells per liter (GI/L) | Standard Deviation 0.6553 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | -0.01 10^9 cells per liter (GI/L) | Standard Deviation 0.0292 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 14, 24 h post dose | -0.864 10^9 cells per liter (GI/L) | Standard Deviation 1.4151 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 14, 24 h post dose | -0.006 10^9 cells per liter (GI/L) | Standard Deviation 0.0261 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | -0.8 10^9 cells per liter (GI/L) | Standard Deviation 18.07 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | 0.102 10^9 cells per liter (GI/L) | Standard Deviation 1.1107 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | -0.02 10^9 cells per liter (GI/L) | Standard Deviation 0.0806 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | -0.036 10^9 cells per liter (GI/L) | Standard Deviation 0.0829 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 14, 24 h post dose | 0.01 10^9 cells per liter (GI/L) | Standard Deviation 0.0122 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | 0.01 10^9 cells per liter (GI/L) | Standard Deviation 0.0187 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | 0.17 10^9 cells per liter (GI/L) | Standard Deviation 1.0481 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | -0.034 10^9 cells per liter (GI/L) | Standard Deviation 0.0702 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 14, 24 h post dose | -0.164 10^9 cells per liter (GI/L) | Standard Deviation 0.7907 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | -0.046 10^9 cells per liter (GI/L) | Standard Deviation 0.0378 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | 0.134 10^9 cells per liter (GI/L) | Standard Deviation 0.801 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | -0.022 10^9 cells per liter (GI/L) | Standard Deviation 0.1326 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 14, 24 h post dose | -7.2 10^9 cells per liter (GI/L) | Standard Deviation 20.41 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | -0.216 10^9 cells per liter (GI/L) | Standard Deviation 0.208 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | 10 10^9 cells per liter (GI/L) | Standard Deviation 24.52 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | 0.926 10^9 cells per liter (GI/L) | Standard Deviation 3.1314 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | 0.004 10^9 cells per liter (GI/L) | Standard Deviation 0.0182 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 14, 24 h post dose | -0.002 10^9 cells per liter (GI/L) | Standard Deviation 0.0192 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | -0.026 10^9 cells per liter (GI/L) | Standard Deviation 0.0498 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | -0.054 10^9 cells per liter (GI/L) | Standard Deviation 0.1498 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | -0.094 10^9 cells per liter (GI/L) | Standard Deviation 0.3092 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | 0.092 10^9 cells per liter (GI/L) | Standard Deviation 0.9722 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | 0.05 10^9 cells per liter (GI/L) | Standard Deviation 0.2108 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | -0.004 10^9 cells per liter (GI/L) | Standard Deviation 0.1313 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | 15.6 10^9 cells per liter (GI/L) | Standard Deviation 17.78 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 14, 24 h post dose | -1.4 10^9 cells per liter (GI/L) | Standard Deviation 44.86 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 14, 24 h post dose | -0.178 10^9 cells per liter (GI/L) | Standard Deviation 2.2899 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | 1.018 10^9 cells per liter (GI/L) | Standard Deviation 2.6669 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | -0.18 10^9 cells per liter (GI/L) | Standard Deviation 1.469 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | 0.093 10^9 cells per liter (GI/L) | Standard Deviation 0.2813 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | 0.022 10^9 cells per liter (GI/L) | Standard Deviation 0.1289 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | 11.7 10^9 cells per liter (GI/L) | Standard Deviation 15.41 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | 0.025 10^9 cells per liter (GI/L) | Standard Deviation 0.1078 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | 0.497 10^9 cells per liter (GI/L) | Standard Deviation 0.8673 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | 0.018 10^9 cells per liter (GI/L) | Standard Deviation 0.1209 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | 0.335 10^9 cells per liter (GI/L) | Standard Deviation 0.5921 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | 0.21 10^9 cells per liter (GI/L) | Standard Deviation 0.3855 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 14, 24 h post dose | 0.007 10^9 cells per liter (GI/L) | Standard Deviation 0.0175 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | 0.03 10^9 cells per liter (GI/L) | Standard Deviation 0.0699 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 14, 24 h post dose | 0.648 10^9 cells per liter (GI/L) | Standard Deviation 1.143 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 14, 24 h post dose | 7 10^9 cells per liter (GI/L) | Standard Deviation 19.81 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | 0.007 10^9 cells per liter (GI/L) | Standard Deviation 0.0052 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | 0.385 10^9 cells per liter (GI/L) | Standard Deviation 1.2151 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | 26.5 10^9 cells per liter (GI/L) | Standard Deviation 32.77 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | -0.243 10^9 cells per liter (GI/L) | Standard Deviation 0.3054 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | -0.118 10^9 cells per liter (GI/L) | Standard Deviation 0.3223 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 14, 24 h post dose | -8.3 10^9 cells per liter (GI/L) | Standard Deviation 51.57 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | 0.023 10^9 cells per liter (GI/L) | Standard Deviation 0.0222 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | 0.5 10^9 cells per liter (GI/L) | Standard Deviation 2.676 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | -0.002 10^9 cells per liter (GI/L) | Standard Deviation 0.0287 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 14, 24 h post dose | 0.825 10^9 cells per liter (GI/L) | Standard Deviation 1.6016 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 14, 24 h post dose | -0.008 10^9 cells per liter (GI/L) | Standard Deviation 0.0189 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | 0.958 10^9 cells per liter (GI/L) | Standard Deviation 1.8925 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | 0.448 10^9 cells per liter (GI/L) | Standard Deviation 2.153 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | 0.165 10^9 cells per liter (GI/L) | Standard Deviation 0.5166 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | -0.005 10^9 cells per liter (GI/L) | Standard Deviation 0.01 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | 0.108 10^9 cells per liter (GI/L) | Standard Deviation 0.3437 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 14, 24 h post dose | 0.01 10^9 cells per liter (GI/L) | Standard Deviation 0.0122 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 7/Day 8, pre-dose | -0.08 10^9 cells per liter (GI/L) | Standard Deviation 0.1398 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 7/Day 8, pre-dose | -0.218 10^9 cells per liter (GI/L) | Standard Deviation 0.6236 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Lymphocytes; Day 14, 24 h post dose | -0.398 10^9 cells per liter (GI/L) | Standard Deviation 0.736 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 7/Day 8, pre-dose | -0.6 10^9 cells per liter (GI/L) | Standard Deviation 14.4 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Monocytes; Day 14, 24 h post dose | -0.11 10^9 cells per liter (GI/L) | Standard Deviation 0.0834 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 7/Day 8, pre-dose | -0.802 10^9 cells per liter (GI/L) | Standard Deviation 0.7889 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 7/Day 8, pre-dose | 0.012 10^9 cells per liter (GI/L) | Standard Deviation 0.0438 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 7/Day 8, pre-dose | -0.51 10^9 cells per liter (GI/L) | Standard Deviation 0.285 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Eosinophils; Day 14, 24 h post dose | 0.022 10^9 cells per liter (GI/L) | Standard Deviation 0.0396 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Platelets; Day 14, 24 h post dose | -11.4 10^9 cells per liter (GI/L) | Standard Deviation 29.39 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Total ANC; Day 14, 24 h post dose | -0.51 10^9 cells per liter (GI/L) | Standard Deviation 0.7931 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | Basophils; Day 7/Day 8, pre-dose | 0 10^9 cells per liter (GI/L) | Standard Deviation 0.01 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of Basophils, Eosinophils, Lymphocytes, Monocytes, Platelets, White Blood Cells (WBC), Total Neutrophils (Total ANC) at the Indicated Time Points | WBC; Day 14, 24 h post dose | -1.012 10^9 cells per liter (GI/L) | Standard Deviation 1.3388 |
Secondary
Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 7/Day 8, pre-dose | 0.076 10^12 cells/Liter (TI/L) | Standard Deviation 0.1148 |
| Part A: Placebo | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 14, 24 h post dose | 0.11 10^12 cells/Liter (TI/L) | Standard Deviation 0.1891 |
| Part A: Placebo | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | -0.00064 10^12 cells/Liter (TI/L) | Standard Deviation 0.01328 |
| Part A: Placebo | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | 0.0034 10^12 cells/Liter (TI/L) | Standard Deviation 0.014934 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | 0.0006 10^12 cells/Liter (TI/L) | Standard Deviation 0.010183 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | 0.00714 10^12 cells/Liter (TI/L) | Standard Deviation 0.020838 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 7/Day 8, pre-dose | 0.036 10^12 cells/Liter (TI/L) | Standard Deviation 0.1549 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 14, 24 h post dose | -0.038 10^12 cells/Liter (TI/L) | Standard Deviation 0.1663 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | 0.01298 10^12 cells/Liter (TI/L) | Standard Deviation 0.011129 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 14, 24 h post dose | 0.034 10^12 cells/Liter (TI/L) | Standard Deviation 0.1785 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 7/Day 8, pre-dose | 0.18 10^12 cells/Liter (TI/L) | Standard Deviation 0.2703 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | 0.01032 10^12 cells/Liter (TI/L) | Standard Deviation 0.015404 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 7/Day 8, pre-dose | 0.058 10^12 cells/Liter (TI/L) | Standard Deviation 0.1314 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 14, 24 h post dose | -0.07 10^12 cells/Liter (TI/L) | Standard Deviation 0.1815 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | 0.01258 10^12 cells/Liter (TI/L) | Standard Deviation 0.014565 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | 0.0156 10^12 cells/Liter (TI/L) | Standard Deviation 0.013092 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 7/Day 8, pre-dose | -0.023 10^12 cells/Liter (TI/L) | Standard Deviation 0.1508 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | -0.00172 10^12 cells/Liter (TI/L) | Standard Deviation 0.005382 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 14, 24 h post dose | -0.083 10^12 cells/Liter (TI/L) | Standard Deviation 0.0958 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | 0.00397 10^12 cells/Liter (TI/L) | Standard Deviation 0.008856 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 14, 24 h post dose | 0.042 10^12 cells/Liter (TI/L) | Standard Deviation 0.1031 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 7/Day 8, pre-dose | 0.14 10^12 cells/Liter (TI/L) | Standard Deviation 0.0879 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | 0.00882 10^12 cells/Liter (TI/L) | Standard Deviation 0.018576 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | -0.01063 10^12 cells/Liter (TI/L) | Standard Deviation 0.018329 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 7/Day 8, pre-dose | 0.01792 10^12 cells/Liter (TI/L) | Standard Deviation 0.012824 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 7/Day 8, pre-dose | -0.058 10^12 cells/Liter (TI/L) | Standard Deviation 0.1252 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | RBC; Day 14, 24 h post dose | -0.084 10^12 cells/Liter (TI/L) | Standard Deviation 0.1496 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Counts of RBCs and Reticulocytes at the Indicated Time Points | Reticulocytes; Day 14, 24 h post dose | 0.00884 10^12 cells/Liter (TI/L) | Standard Deviation 0.015546 |
Secondary
Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | 1.58 Micromoles/Liter (micromol/L) | Standard Deviation 7.276 |
| Part A: Placebo | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | -0.1 Micromoles/Liter (micromol/L) | Standard Deviation 0.453 |
| Part A: Placebo | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | -0.5 Micromoles/Liter (micromol/L) | Standard Deviation 3.389 |
| Part A: Placebo | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | -0.02 Micromoles/Liter (micromol/L) | Standard Deviation 0.327 |
| Part A: Placebo | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | 0.28 Micromoles/Liter (micromol/L) | Standard Deviation 2.255 |
| Part A: Placebo | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | 4.52 Micromoles/Liter (micromol/L) | Standard Deviation 4.533 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | 0.24 Micromoles/Liter (micromol/L) | Standard Deviation 0.493 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | 0.08 Micromoles/Liter (micromol/L) | Standard Deviation 0.87 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | 0.76 Micromoles/Liter (micromol/L) | Standard Deviation 3.319 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | -0.02 Micromoles/Liter (micromol/L) | Standard Deviation 0.192 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | 1.6 Micromoles/Liter (micromol/L) | Standard Deviation 3.77 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | 0.56 Micromoles/Liter (micromol/L) | Standard Deviation 2.151 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | 4.38 Micromoles/Liter (micromol/L) | Standard Deviation 2.217 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | -0.7 Micromoles/Liter (micromol/L) | Standard Deviation 4.049 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | 4.84 Micromoles/Liter (micromol/L) | Standard Deviation 4.636 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | -2.08 Micromoles/Liter (micromol/L) | Standard Deviation 2.387 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | -0.28 Micromoles/Liter (micromol/L) | Standard Deviation 0.881 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | -0.58 Micromoles/Liter (micromol/L) | Standard Deviation 0.581 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | -0.3 Micromoles/Liter (micromol/L) | Standard Deviation 4.567 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | 0.16 Micromoles/Liter (micromol/L) | Standard Deviation 0.261 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | 0.22 Micromoles/Liter (micromol/L) | Standard Deviation 0.409 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | 0.72 Micromoles/Liter (micromol/L) | Standard Deviation 2.196 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | 0.52 Micromoles/Liter (micromol/L) | Standard Deviation 2.7 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | -0.46 Micromoles/Liter (micromol/L) | Standard Deviation 6.98 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | 1.22 Micromoles/Liter (micromol/L) | Standard Deviation 3.008 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | 0.2 Micromoles/Liter (micromol/L) | Standard Deviation 0.429 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | 0.52 Micromoles/Liter (micromol/L) | Standard Deviation 4.397 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | 2.05 Micromoles/Liter (micromol/L) | Standard Deviation 3.17 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | 1.08 Micromoles/Liter (micromol/L) | Standard Deviation 2.775 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | 0.23 Micromoles/Liter (micromol/L) | Standard Deviation 0.65 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | -0.86 Micromoles/Liter (micromol/L) | Standard Deviation 1.75 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | 0.5 Micromoles/Liter (micromol/L) | Standard Deviation 2.804 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | 0.02 Micromoles/Liter (micromol/L) | Standard Deviation 0.554 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | 3.48 Micromoles/Liter (micromol/L) | Standard Deviation 3.084 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | -0.18 Micromoles/Liter (micromol/L) | Standard Deviation 1.36 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | 1.36 Micromoles/Liter (micromol/L) | Standard Deviation 2.545 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 7/Day 8, pre-dose | -1.5 Micromoles/Liter (micromol/L) | Standard Deviation 1.739 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 14, 24 h post dose | -0.14 Micromoles/Liter (micromol/L) | Standard Deviation 0.456 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 14, 24 h post dose | 1.42 Micromoles/Liter (micromol/L) | Standard Deviation 5.058 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Total bilirubin; Day 14, 24 h post dose | -1.06 Micromoles/Liter (micromol/L) | Standard Deviation 1.479 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Creatinine; Day 7/Day 8, pre-dose | 0.76 Micromoles/Liter (micromol/L) | Standard Deviation 5.421 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Creatinine, Bilirubin, and Total Bilirubin at the Indicated Time Points | Direct bilirubin; Day 7/Day 8, pre-dose | -0.32 Micromoles/Liter (micromol/L) | Standard Deviation 0.37 |
Secondary
Part B: Change From Baseline in Hematocrit at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.012 Ratio | Standard Deviation 0.0084 |
| Part A: Placebo | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 14, 24 h post dose | 0.008 Ratio | Standard Deviation 0.0217 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.004 Ratio | Standard Deviation 0.0182 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 14, 24 h post dose | 0 Ratio | Standard Deviation 0.0212 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.018 Ratio | Standard Deviation 0.0259 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 14, 24 h post dose | 0.006 Ratio | Standard Deviation 0.0152 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.01 Ratio | Standard Deviation 0.01 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 14, 24 h post dose | -0.012 Ratio | Standard Deviation 0.0217 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 7/Day 8, pre-dose | 0 Ratio | Standard Deviation 0.0141 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 14, 24 h post dose | -0.01 Ratio | Standard Deviation 0.0063 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.015 Ratio | Standard Deviation 0.0058 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 14, 24 h post dose | 0.01 Ratio | Standard Deviation 0.0082 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 7/Day 8, pre-dose | -0.010 Ratio | Standard Deviation 0.0235 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Hematocrit at the Indicated Time Points | Day 14, 24 h post dose | -0.004 Ratio | Standard Deviation 0.0207 |
Secondary
Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. MCHC is one of the red blood cell (RBC) indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | 3 g/L | Standard Deviation 2.55 |
| Part A: Placebo | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | 4.2 g/L | Standard Deviation 6.14 |
| Part A: Placebo | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | -2.4 g/L | Standard Deviation 2.07 |
| Part A: Placebo | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | 3.8 g/L | Standard Deviation 5.07 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | -2.6 g/L | Standard Deviation 3.51 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | -0.6 g/L | Standard Deviation 8.17 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | 0.8 g/L | Standard Deviation 5.76 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | -1.2 g/L | Standard Deviation 6.14 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | -4.0 g/L | Standard Deviation 7.31 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | -0.6 g/L | Standard Deviation 8.02 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | 3.8 g/L | Standard Deviation 6.76 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | -4.4 g/L | Standard Deviation 8.73 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | 1 g/L | Standard Deviation 4.74 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | -2 g/L | Standard Deviation 6.86 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | -4.4 g/L | Standard Deviation 9.61 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | 3.0 g/L | Standard Deviation 4 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | 0.3 g/L | Standard Deviation 5.65 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | 2.5 g/L | Standard Deviation 3.83 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | -2.2 g/L | Standard Deviation 2.14 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | 0.5 g/L | Standard Deviation 5.17 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | -0.3 g/L | Standard Deviation 4.65 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | 6 g/L | Standard Deviation 5.89 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | 3.3 g/L | Standard Deviation 8.18 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | -8.5 g/L | Standard Deviation 7.59 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 7/Day 8, pre-dose | 7.8 g/L | Standard Deviation 10.85 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 7/Day 8, pre-dose | 1 g/L | Standard Deviation 3.39 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | Hemoglobin; Day 14, 24 h post dose | -0.2 g/L | Standard Deviation 4.44 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points | MCHC; Day 14, 24 h post dose | 1.6 g/L | Standard Deviation 11.76 |
Secondary
Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. MCH is one of the red blood cell indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.18 pg | Standard Deviation 0.415 |
| Part A: Placebo | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 14, 24 h post dose | 0.18 pg | Standard Deviation 0.626 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 7/Day 8, pre-dose | -0.06 pg | Standard Deviation 0.397 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 14, 24 h post dose | 0.02 pg | Standard Deviation 0.259 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 7/Day 8, pre-dose | -0.36 pg | Standard Deviation 0.351 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 14, 24 h post dose | -0.34 pg | Standard Deviation 0.74 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 7/Day 8, pre-dose | -0.08 pg | Standard Deviation 0.669 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 14, 24 h post dose | 0.12 pg | Standard Deviation 0.396 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.2 pg | Standard Deviation 0.529 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 14, 24 h post dose | 0.1 pg | Standard Deviation 0.363 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.35 pg | Standard Deviation 0.961 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 14, 24 h post dose | -0.33 pg | Standard Deviation 0.754 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 7/Day 8, pre-dose | 0.58 pg | Standard Deviation 0.46 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points | Day 14, 24 h post dose | 0.52 pg | Standard Deviation 0.268 |
Secondary
Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Blood samples were collected for measurement for the indicated tests. MCV is one of the RBC indices. Change from Baseline at any post-dose visit was calculated as the post-dose visit value minus the Baseline value. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Baseline (Day 1 [pre-dose]), Day 7 (pre-dose), and Day 14 (24 hours [h] post-dose)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | 1.24 fL | Standard Deviation 0.706 |
| Part A: Placebo | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | -0.66 fL | Standard Deviation 1.537 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | -0.14 fL | Standard Deviation 1.794 |
| Part A: GSK2269577 1000 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | 0.80 fL | Standard Deviation 1.257 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | -0.12 fL | Standard Deviation 1.708 |
| Part B: GSK2269577 200 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | 0.26 fL | Standard Deviation 1.935 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | 0.88 fL | Standard Deviation 1.085 |
| Part B: GSK2269577 500 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | -0.62 fL | Standard Deviation 1.281 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | 0.42 fL | Standard Deviation 2.302 |
| Part B: GSK2269577 700 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | -0.53 fL | Standard Deviation 1.601 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | 0.20 fL | Standard Deviation 0.583 |
| Part B: GSK2269577 1000 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | 1.53 fL | Standard Deviation 0.699 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 7/Day 8, pre-dose | -0.70 fL | Standard Deviation 2.719 |
| Part B: GSK2269577 2000 µg | Part B: Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points | MCV; Day 14, 24 h post dose | 0.98 fL | Standard Deviation 3.155 |
Secondary
Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose
A 2 mL blood sample for pharmacokinetic (PK) analysis was collected at each of the indicated time point. Concentration measurements were log-transformed. Only those participants who were available at the indicated time points were analyzed (represented by n=X,X in the category titles). A value of NA indicates that the geometric mean or 95% confidence interval is not available.
Time frame: Pre-dose, and 5 min, 30 min, 1 h, 2 h, 4 h, and 6 h post-dose on Day 1
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Placebo | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Pre-dose; n=0,0,0,0,0,0 | NA pg/mL |
| Part A: Placebo | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 2 h; n=5,5,5,6,5,5 | 60.6 pg/mL |
| Part A: Placebo | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 5 min; n=5,5,5,6,5,5 | 55.3 pg/mL |
| Part A: Placebo | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 6 h; n=5,5,5,6,5,5 | 38.3 pg/mL |
| Part A: Placebo | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 30 min; n=5,5,5,6,5,5 | 51.7 pg/mL |
| Part A: Placebo | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 4 h; n=5,5,5,6,5,5 | 45.0 pg/mL |
| Part A: Placebo | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 1 h; n=5,5,5,6,5,5 | 61.3 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 5 min; n=5,5,5,6,5,5 | 80.4 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 1 h; n=5,5,5,6,5,5 | 77.2 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 30 min; n=5,5,5,6,5,5 | 73.8 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 2 h; n=5,5,5,6,5,5 | 88.8 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Pre-dose; n=0,0,0,0,0,0 | NA pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 6 h; n=5,5,5,6,5,5 | 63.8 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 4 h; n=5,5,5,6,5,5 | 73.4 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 30 min; n=5,5,5,6,5,5 | 203 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 5 min; n=5,5,5,6,5,5 | 173.1 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Pre-dose; n=0,0,0,0,0,0 | NA pg/mL |
| Part B: GSK2269577 200 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 2 h; n=5,5,5,6,5,5 | 300.9 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 4 h; n=5,5,5,6,5,5 | 251 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 1 h; n=5,5,5,6,5,5 | 253.2 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 6 h; n=5,5,5,6,5,5 | 201.5 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 1 h; n=5,5,5,6,5,5 | 429.1 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Pre-dose; n=0,0,0,0,0,0 | NA pg/mL |
| Part B: GSK2269577 500 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 5 min; n=5,5,5,6,5,5 | 466.6 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 30 min; n=5,5,5,6,5,5 | 402.3 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 2 h; n=5,5,5,6,5,5 | 556.7 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 4 h; n=5,5,5,6,5,5 | 391.6 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 6 h; n=5,5,5,6,5,5 | 294.6 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 30 min; n=5,5,5,6,5,5 | 556.9 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 5 min; n=5,5,5,6,5,5 | 853.4 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 6 h; n=5,5,5,6,5,5 | 466.5 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Pre-dose; n=0,0,0,0,0,0 | NA pg/mL |
| Part B: GSK2269577 700 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 4 h; n=5,5,5,6,5,5 | 468.7 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 1 h; n=5,5,5,6,5,5 | 599.7 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 2 h; n=5,5,5,6,5,5 | 672.3 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 6 h; n=5,5,5,6,5,5 | 900.8 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 2 h; n=5,5,5,6,5,5 | 1402 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 30 min; n=5,5,5,6,5,5 | 1011.6 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 5 min; n=5,5,5,6,5,5 | 982.9 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 4 h; n=5,5,5,6,5,5 | 1098.5 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | Pre-dose; n=0,0,0,0,0,0 | NA pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Day 1 Plasma Concentration of GSK2269577 up to 6 Hours Post Dose | 1 h; n=5,5,5,6,5,5 | 1203.3 pg/mL |
Secondary
Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up
FEV1 and FVC are measures of lung function. FEV1 is defined as the maximal amount of air that can be forcefully exhaled in one second. FVC is defined as the maximum amount of air that can be forcibly blown out after a maximum inspiration. FEV1 and FVC measurements were repeated until three technically acceptable measurements (within 150 milliliters of each other) had been made. Only the best of three measurements were recorded.
Time frame: Screening (up to 30 days prior to Day 1) and Follow-up (approximately Day 19)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A: Placebo | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Follow-up | 1.494 Liters |
| Part A: Placebo | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Follow-up | 2.96 Liters |
| Part A: Placebo | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Screening | 1.586 Liters |
| Part A: Placebo | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Screening | 3.05 Liters |
| Part A: GSK2269577 1000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Screening | 1.387 Liters |
| Part A: GSK2269577 1000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Follow-up | 1.272 Liters |
| Part A: GSK2269577 1000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Screening | 3.08 Liters |
| Part A: GSK2269577 1000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Follow-up | 3.042 Liters |
| Part B: GSK2269577 200 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Follow-up | 1.523 Liters |
| Part B: GSK2269577 200 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Screening | 1.533 Liters |
| Part B: GSK2269577 200 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Follow-up | 3.764 Liters |
| Part B: GSK2269577 200 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Screening | 3.632 Liters |
| Part B: GSK2269577 500 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Follow-up | 4.192 Liters |
| Part B: GSK2269577 500 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Screening | 4.348 Liters |
| Part B: GSK2269577 500 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Screening | 1.558 Liters |
| Part B: GSK2269577 500 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Follow-up | 1.34 Liters |
| Part B: GSK2269577 700 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Follow-up | 3.137 Liters |
| Part B: GSK2269577 700 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Follow-up | 1.501 Liters |
| Part B: GSK2269577 700 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Screening | 1.573 Liters |
| Part B: GSK2269577 700 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Screening | 3.277 Liters |
| Part B: GSK2269577 1000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Screening | 2.958 Liters |
| Part B: GSK2269577 1000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Follow-up | 3.03 Liters |
| Part B: GSK2269577 1000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Screening | 1.36 Liters |
| Part B: GSK2269577 1000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Follow-up | 1.405 Liters |
| Part B: GSK2269577 2000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Follow-up | 1.431 Liters |
| Part B: GSK2269577 2000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Follow-up | 3.192 Liters |
| Part B: GSK2269577 2000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FVC, Screening | 3.156 Liters |
| Part B: GSK2269577 2000 µg | Part B: Forced Expiratory Volume in One Second (FEV1) and Forced Vital Capacity (FVC) at Screening and Follow-up | FEV1, Screening | 1.407 Liters |
Secondary
Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7
Blood samples were collected to determine the plasma concentrations of GSK2269577 immediately after dosing on Day 7. Concentration values were log-transformed. Day 7 sampling could be done on Day 7 or Day 8.
Time frame: Day 7 immediately after dosing
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Placebo | Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | 109.6 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | 203.4 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | 511.8 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | 1022.2 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | 1655.1 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Maximum Observed Plasma Concentration (Cmax) of GSK2269577 on Day 7 | 2923.4 pg/mL |
Secondary
Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline
Baseline was the Day 1 pre-dose measurement. Vital signs (SBP, DBP, and HR) were measured at Day 1 (30 minutes \[min\] and 6 h post-dose), Day 7 (pre-dose), and Day 14 (24 h post-dose). All measurements were obtained in supine position, after a 5-minute rest. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Day 1, Day 7, and Day 14
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part A: Placebo | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 0 Participants |
| Part A: Placebo | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
| Part A: Placebo | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part A: Placebo | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 0 Participants |
| Part A: Placebo | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 0 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 0 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 0 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 0 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 0 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 0 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 1 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 1 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 0 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 0 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 1 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 0 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 0 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 0 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 0 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 0 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP low | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP low | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | SBP high | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR low | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | HR high | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants Meeting Criteria of Potential Clinical Importance for Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Heart Rate (HR) at Any Visit Post-Baseline | DBP high | 0 Participants |
Secondary
Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5. AEs were classified as potentially drug-related, based on the investigator's judgment. Refer to the general AE/SAE module for a list of AEs and SAEs.
Time frame: From the start of study treatment until follow-up (assessed for approximately 19 days)
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 0 Participants |
| Part A: Placebo | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 0 Participants |
| Part A: Placebo | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 3 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 0 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 3 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 0 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 1 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 2 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 0 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 0 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 1 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 0 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 0 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 3 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 3 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 4 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 4 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one drug-related AE | 2 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one SAE | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants With at Least One Non-serious Adverse Event (AE), Serious Adverse Event (SAE), or Drug-related Adverse Event | At least one AE | 2 Participants |
Secondary
Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline
Baseline was the Day 1 (pre-dose) measurement. Single 12-lead ECGs were obtained using an ECG machine that automatically calculates the HR and measures PR, QRS, QT, and corrected QT intervals. Day 7 assessments could be conducted on Day 7 or Day 8.
Time frame: Day 1, Day 7, and Day 14
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Placebo | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
| Part A: Placebo | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 1 Participants |
| Part A: Placebo | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 4 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 0 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 5 Participants |
| Part A: GSK2269577 1000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 3 Participants |
| Part B: GSK2269577 200 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 2 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 3 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 2 Participants |
| Part B: GSK2269577 500 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 1 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 5 Participants |
| Part B: GSK2269577 700 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 5 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
| Part B: GSK2269577 1000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - clinically significant | 0 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Abnormal - not clinically significant | 1 Participants |
| Part B: GSK2269577 2000 µg | Part B: Number of Participants With Normal and Abnormal (Clinically Significant or Not Clinically Significant) Findings in 12-lead Electrocardiogram (ECG) at Any Visit Post-Baseline | Normal | 4 Participants |
Secondary
Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period
Rescue medication was identified from concomitant medication records and the patient diaries which were provided to the participants to record data throughout the treatment period. Only participants who used rescue medication were analyzed. The value NA indicates that the standard deviation could not be calculated as only one participant was analyzed.
Time frame: Day 1 to Day 15
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period | 2.00 Number of times | Standard Deviation 0 |
| Part A: GSK2269577 1000 µg | Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period | 2.3 Number of times | — |
| Part B: GSK2269577 200 µg | Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period | 2.2 Number of times | — |
| Part B: GSK2269577 700 µg | Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period | 1.0 Number of times | — |
| Part B: GSK2269577 1000 µg | Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period | 1.4 Number of times | Standard Deviation 0.63 |
| Part B: GSK2269577 2000 µg | Part B: Number of Times Rescue Medication Was Used by Participants Daily, During the Treatment Period | 1.0 Number of times | — |
Secondary
Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15
Blood samples were collected to determine the (trough) plasma concentration of GSK2269577 on Day 7 (pre-dose) and Day 15 (24 hours after dosing on Day 14). Day 7 assessments could be done either on Day 7 or on Day 8.
Time frame: Day 7 and Day 15
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: Placebo | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7/Day 8 | 55.3 pg/mL |
| Part A: Placebo | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 15 | 74.93 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7/Day 8 | 119.17 pg/mL |
| Part A: GSK2269577 1000 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 15 | 128.71 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7/Day 8 | 314.38 pg/mL |
| Part B: GSK2269577 200 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 15 | 237.36 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7/Day 8 | 588.09 pg/mL |
| Part B: GSK2269577 500 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 15 | 665.9 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7/Day 8 | 724.33 pg/mL |
| Part B: GSK2269577 700 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 15 | 1218.5 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 7/Day 8 | 1468.94 pg/mL |
| Part B: GSK2269577 1000 µg | Part B: Trough Concentration (Ctau) of GSK2269577 on Day 7 and Day 15 | Day 15 | 1767.34 pg/mL |