Urticaria
Conditions
Keywords
Urticaria, SYK Inhibitor
Brief summary
This First Time in Human (FTIH) study, which will be performed in three parts, is designed to investigate the safety, local tolerability, pharmacokinetics and pharmacodynamics after single and repeat topical applications of up to 2 strengths of GSK2646264 and corresponding placebo within the same subject, in healthy adult subjects (Part A), subjects with cold urticaria (CU, Part B) and subjects with chronic spontaneous urticaria (CsU, Part C). The study will also measure short term effects of GSK2646264 on the number and size of weals in subjects with CsU, and in healthy subjects and subjects with CU following provocation tests.
Interventions
DRUGGSK2646264 0.5% topical cream
GSK2646264 0.5% topical cream is supplied as white-to-off-white aqueous cream stored in amber glass jars
DRUGGSK2646264 1% topical cream
GSK2646264 1% topical cream is supplied as white-to-off-white aqueous cream stored in amber glass jars
DRUGPlacebo
Placebo topical cream is supplied as white-to-off-white aqueous cream stored in amber glass jars
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
for all subjects in Parts A, B and C * Male or female subject aged at least 18 years (Yrs) at the time of signing the informed consent. The upper age limit of subjects is defined in the specific inclusion criteria for each cohort. * All subjects must be free from scarring or skin markings (e.g. tattoos or piercings) and open wounds (e.g. scarring or skin markings) on the defined areas of the body that cream will be applied onto, unless in the opinion of the investigator it will not compromise the subjects safety and quality of data. * Able to refrain from exposure to extended and direct sunlight during the study period, from screening (SCR) until follow up, especially the area that is under treatment during the study. * Able to refrain from shaving and waxing the areas on which the study cream will be applied during the duration of the study from SCR to follow up. * Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until the follow up visit or a time period that is 5 terminal half-live post-last dose which will be determined following Part A of the study. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Willing, committed and able to return for all clinic visits and complete all study-related procedures. Able to read, understand and complete study- related questionnaires. Inclusion criteria specific for healthy subjects (Part A) * The subject is aged between 18 and 55 yrs of age inclusive, at the time of signing the informed consent. * Body weight \>=50 kilogram (kg) and body mass index (BMI) within the range 19 to 30 kg per square meter (m\^2 )(inclusive). * Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. 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 only if the Investigator, in consultation with the GSK Medical Monitor (MM) if required, agrees and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Demonstration of a positive weal and flare reaction (\>=3 millimeter (mm) in diameter relative to negative control) to at least one allergen from a battery of allergens (mixed grass pollen, Dermatophagoides pteronyssinus, birch pollen and cat dander) on skin prick testing at SCR. * Subjects must be free from any past or present benign or malignant skin conditions and disease, unless in the opinion of the investigator it will not compromise the subject's safety and quality of data. * Non-smokers or if the subject is a tobacco smoke: smokes less than 5 cigarettes per day and commits to not smoke tobacco for the duration of the in-house stay, and commits to stable and moderate use (as determined by the Investigator) of tobacco or nicotine-containing products, including nicotine patches/gum, during the course of the study, as long as the patches do not interfere with the study procedures. * A female subject is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy for this definition, documented refers to the outcome of the investigator's/designee's review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records; or postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \>40 milli international unit \[MlU\]/milliliter \[mL\] and estradiol \<40 picogram (pg)/mL (\<147 picomoles/litre) 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 described 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. Additional Inclusion criteria specific for subjects with CU (Part B) * Diagnosed with CU for more than six weeks as confirmed by medical history and with a positive cold stimulation test assessed by TEMPTest 4.0 prior to first dose. * The subject is aged between 18 and 70 yrs of age inclusive, at the time of signing the informed consent. * Body weight \>=50 kg and BMI within the range 19 to 35 kg/m\^2 (inclusive). * Other than a diagnosis of CU, the subject should have no other co-morbidities which would introduce additional risk factors and will not interfere with the study procedures, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tolerability Assessment for Part C | Up to Day 7 | Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed. |
| Number of Participants With AEs and SAEs Defined by Severity Part B | Up to 19 days | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities. Data is presented according to the percentage BSA as it impacted safety |
| Number of Participants With AEs and SAEs Defined by Severity Part C | Up to 23 days | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities. |
| Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7) | Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2, Day 3, Day 4 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. |
| Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19) | Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. |
| Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Baseline and (Day 1 pre-dose), Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15, follow-up (Day 23) | Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. |
| Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7) | Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2, Day 3, Day 4 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. |
| Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11) | Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. |
| Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19) | Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. |
| Change From Baseline in Vital Sign SBP and DBP for Part C | Baseline (Day 1 pre-dose) and Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up (Day 23) | Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. |
| Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | Baseline (Day -1) and Day 4, and follow-up (Day 5 to Day 7) | Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, corrected QT (QTc-Bazett \[QTcB\], QTC interval-Fredericia \[QTcF\]) intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value. |
| Change From Baseline in ECG Parameters for Part B | Baseline (Day -1) and Day 3 (pre-dose) and follow-up (Day 17 to Day 19) | Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value. |
| Change From Baseline in ECG Parameters for Part C | Baseline (Day -1) and Day 7 (pre-dose) and follow-up (Day 23) | Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed. |
| Number of Participants With Clinical Chemistry Data Outside the Range of Potential Clinical Importance (PCI) for Part A | Day 4 and follow up (Day 5 to Day 7) | Clinical chemistry parameters assessed were alanine amino transferase (ALT), albumin (low \<30 grams/liter), alkaline phosphatase, aspartate aminotransferase (AST), calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride, creatinine (high \>159 micromoles/liter), direct bilirubin, gamma glutamyl transferase (GGT low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/blood urea nitrogen (BUN). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented. |
| Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A | Day 5, Day 7 and follow up (Day 9 to Day 11) | Clinical chemistry parameters assessed were alanine amino transferase (ALT), albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride, creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/BUN). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented. |
| Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Day 3 and follow up (Day 17 to Day 19) | Clinical chemistry parameters assessed were ALT, albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride (low \<98 millimoles/liter and high \>106 millimoles/liter), creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/BUN (low \<2.9 and high \>7.1). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented. |
| Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Day 1, Day 7 and follow up (Day 23) | Clinical chemistry parameters assessed were ALT, albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride (low \<98 millimoles/liter and high \>106 millimoles/liter), creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein (low \<60 grams/liter and high \>78 grams/liter) and urea/BUN (low \<2.9 millimoles/liter and high \>7.1 millimoles/liter). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented. |
| Number of Participants With Hematology Data Outside the Range of PCI for Part A | Day 4 and follow up (Day 5 to Day 7) | Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), mean corpuscle hemoglobin (MCH low \<28 picograms and high \>32 picograms), mean corpuscle hemoglobin concentration (MCHC low \<32 grams/liter and high \>36 grams/liter), mean corpuscle volume (MCV), monocytes (high \>0.208x 10\^9 cells/Liter), platelet count, red blood cell (RBC low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and white blood cell (WBC) count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented. |
| Number of Participants With Hematology Data Outside the Range of PCI for Part B | Day 3 and follow up (Day 17 to 19) | Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), MCH (low \<28 picograms and high \>32 picograms), MCHC (low \<32 grams/liter and high \>36 grams/liter), MCV, monocytes (high \>0.208x10\^9 cells/Liter), platelet count, RBC count (low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented. |
| Number of Participants With Hematology Data Outside the Range of PCI for Part C | Day 1, Day 7 and follow up (Day 23) | Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), MCH (low \<28 picograms and high \>32 picograms), MCHC low \<32 grams/liter and high \>36 grams/liter), MCV, monocytes (high \>0.208x10\^9 cells/Liter), platelet count, RBC count (low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented. |
| Number of Participants With Tolerability Assessment for Part A | Up to Day 4 | Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed. |
| Number of Participants With Tolerability Assessment for Part B | Up to Day 3 | Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed. |
| Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A | Up to Day 7 | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all participants who took at least one dose of study treatment. |
| Number of Participants With AEs and SAEs Part A | Up to Day 11 | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. |
| Number of Participants With AEs and SAEs Part B | Up to Day 19 | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Data is presented according to the percentage BSA as it impacted safety |
| Number of Participants With AEs and SAEs Part C | Up to Day 23 | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. |
| Number of Participants With AEs and SAEs Defined by Severity Part A | Up to Day 7 | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma GSK2646264 PK Concentrations for Part B | Day 1 (Pre-dose,1,4,8,12,24 hours), Day 2 (1,4,8,12,24 hours), Day 3 (1,4,8,12,24 hours), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to 19) | Blood samples were collected to assess the plasma concentration of GSK2646264 for Part B on Day 1 (Pre-dose,1,4,8,12,24 hours), Day 2 (1,4,8,12,24 hours), Day 3 (1,4,8,12,24 hours), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to 19). The actual date and time of each blood sample collection was recorded. |
| Plasma GSK2646264 PK Concentrations for Part C | Day 1 (Pre-dose,1 and 4 hours), Day 4 (Pre-dose and 4 hours), Day 7 (Pre-dose and 4 hours), Day 10, Day 15 and follow-up (Day 23) | Blood samples were collected to assess the plasma concentration of GSK2646264 for Part C on Day 1 (Pre-dose,1 and 4 hours), Day 4 (Pre-dose and 4 hours), Day 7 (Pre-dose and 4 hours), Day 10, Day 15 and follow-up. The actual date and time of each blood sample collection was recorded. |
| Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A | Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-T) was determined using the currently approved and validated software. |
| AUC (0-t) of GSK2646264 for Part A | Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-T) was determined using the currently approved and validated software. |
| Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A | Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software. |
| Cmax of GSK2646264 for Part A | Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose | Blood samples were collected at the indicated time points to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software. |
| Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A | Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software. NA indicated data was not collected due to insufficient participants with data. |
| Time to Cmax (Tmax) of GSK2646264 for Part A | Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3 | Blood samples were collected at the indicated time points to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software. |
| Tmax of GSK2646264 for Part A | Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software. |
| Terminal Half-life (t1/2) of GSK2646264 for Part A | Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data. |
| t1/2 of GSK2646264 for Part A | Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours) | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data. |
| AUC [0-t] of GSK2646264 for Part B | Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-t) was determined using the currently approved and validated software. |
| Cmax of GSK2646264 for Part B | Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 (Day 4) | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software. |
| AUC (0-24) of GSK2646264 for Part B | Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 (Day 4) | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software. NA indicates that geometric coefficient of variation could not be computed for Part B (3.5% BSA) GSK2646264 1% as a single participant was analyzed on Day 2. |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B | Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-infinity) was determined using the currently approved and validated software. |
| Terminal Half-life (t1/2) of GSK2646264 for Part B | Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. |
| Tmax of GSK2646264 for Part B | Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software. |
| Cmax of GSK2646264 for Part C | Pre dose and 4 hours post-dose on Days 1, 4 and 7 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software. |
| Tmax of GSK2646264 for Part C | Pre dose and 4 hours post-dose on Days 1, 4 and 7 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software. |
| t1/2 of GSK2646264 for Part C | Pre dose and 4 hours post-dose on Days 1, 4 and 7 | Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated data was not collected due to insufficient number of participants with data to calculate half life. |
| Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours) and Day 3 (1,2,4,8,12,24 hours) | Blood samples were collected to assess the plasma concentration of GSK2646264 for Part A on Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours) and Day 3 (1,2,4,8,12,24 hours). The actual date and time of each blood sample collection was recorded. PK Population comprised of all randomized participants of the Safety Population for whom a pharmacokinetic sample was obtained and analyzed. |
Countries
Germany, United Kingdom
Participant flow
Recruitment details
This study was conducted from 17-November-2014 to 10-November-2017 at centers two centers in the United Kingdom and two centers in Germany.
Pre-assignment details
92 participants were screened (3 re-screened) of which 58 were screen failures. Hence 34 participants, 17 healthy participants (Part A), 12 participants with cold urticaria (CU, Part B) and 5 participants with chronic spontaneous urticaria (CsU, Part C) were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Part A-GSK2646264 0.5% and Placebo Participants were treated topically with 0.5 % GSK2646264 cream and placebo cream on an area of approximately 12 x 3 cm on the volar aspect of the arm which approximated to 0.2% total BSA, on each arm. On Day 2 and Day 3 participants received active treatment and placebo on the same arms as on Day 1, with the percentage BSA being 1% on Day 2 and 5% on Day 3. | 9 |
| Part A-GSK2646264 1% and Placebo Participants received active treatment (1% cream strength) and placebo on Days 1, 2, 3 and 4. On Day 1 and Day 2, participants received treatment to 0.2% BSA; active treatment on one arm and placebo on the other arm. In addition, participants received treatment to another 5% BSA; active to one side of the torso and placebo to the other. On Days 3 and 4, the same treatment to the arms was applied as on Days 1 and 2, but the %BSA of the torso to which treatment was applied to was increased to 10%. | 8 |
| Part B-Placebo CU participants received matching placebo treatment to an area of 10% BSA (5% BSA on each arm, n=1) or 3.5% BSA (spread over the 2 arms, n=2) on days 1, 2 and 3. | 3 |
| Part B GSK2646264 1% CU participants received 1% strength GSK2646264 to an area of 10% BSA (5% BSA on each arm, n=3) or 3% BSA (spread over the 2 arms, n=6) on days 1, 2 and 3. | 9 |
| Part C-Placebo CSU participants received matching placebo treatment to 10% BSA (arms, legs or torso) on Days 1, 4 and 7. | 1 |
| Part C GSK2646264 1% CSU participants received 1% strength GSK2646264 to 10% BSA (arms, legs or torso) on Days 1, 4 and 7. | 4 |
| Total | 34 |
Baseline characteristics
| Characteristic | Part A-GSK2646264 0.5% and Placebo | Part A-GSK2646264 1% and Placebo | Part B-Placebo | Part B GSK2646264 1% | Part C-Placebo | Part C GSK2646264 1% | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.0 Years STANDARD_DEVIATION 10.74 | 38.9 Years STANDARD_DEVIATION 11.54 | 41.3 Years STANDARD_DEVIATION 10.07 | 50.7 Years STANDARD_DEVIATION 11.7 | 24.0 Years | 50.8 Years STANDARD_DEVIATION 12.58 | 42.9 Years STANDARD_DEVIATION 12.47 |
| Race/Ethnicity, Customized White-Arabic/North African Heritage | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White/Caucasian/European Heritage | 9 Participants | 8 Participants | 3 Participants | 8 Participants | 0 Participants | 4 Participants | 32 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 7 Participants | 1 Participants | 4 Participants | 17 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 17 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 8 | 0 / 1 | 0 / 3 | 0 / 2 | 0 / 6 | 0 / 1 | 0 / 4 |
| other Total, other adverse events | 4 / 9 | 4 / 8 | 1 / 1 | 3 / 3 | 0 / 2 | 3 / 6 | 1 / 1 | 1 / 4 |
| serious Total, serious adverse events | 0 / 9 | 0 / 8 | 0 / 1 | 0 / 3 | 0 / 2 | 0 / 6 | 0 / 1 | 0 / 4 |
Outcome results
Primary
Change From Baseline in ECG Parameters for Part B
Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day -1) and Day 3 (pre-dose) and follow-up (Day 17 to Day 19)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | Uncorrected QT Interval , Follow-up | 1.33 milliseconds | Standard Deviation 18.583 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | PR interval, Follow-up | 3.33 milliseconds | Standard Deviation 11.547 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | QRS duration, Day 3 Pre-dose | -6.00 milliseconds | Standard Deviation 12.166 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | QRS duration, Follow-up | -4.67 milliseconds | Standard Deviation 8.083 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | QTcB, Day 3, Pre-dose | -13.00 milliseconds | Standard Deviation 6.083 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | QTcB, Follow-up | -5.33 milliseconds | Standard Deviation 21.733 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | QTcF, Day 3, Pre-dose | -6.33 milliseconds | Standard Deviation 10.017 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | QTcF, Follow-up | -3.00 milliseconds | Standard Deviation 20.298 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | RR interval, Day 3, Pre-dose | 95.33 milliseconds | Standard Deviation 74.07 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | RR interval, Follow-up | 30.00 milliseconds | Standard Deviation 59.355 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | Uncorrected QT Interval , Day 3, Pre-dose | 6.67 milliseconds | Standard Deviation 19.218 |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part B | PR interval, Day 3 Pre-dose | -6.67 milliseconds | Standard Deviation 5.774 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | Uncorrected QT Interval , Follow-up | 3.78 milliseconds | Standard Deviation 10.745 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | PR interval, Day 3 Pre-dose | 5.56 milliseconds | Standard Deviation 10.138 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | QTcF, Day 3, Pre-dose | -5.00 milliseconds | Standard Deviation 11.203 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | PR interval, Follow-up | -2.22 milliseconds | Standard Deviation 10.929 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | RR interval, Follow-up | 38.33 milliseconds | Standard Deviation 86.51 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | QRS duration, Day 3 Pre-dose | -2.44 milliseconds | Standard Deviation 2.789 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | QTcF, Follow-up | -1.78 milliseconds | Standard Deviation 6.906 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | QRS duration, Follow-up | -2.44 milliseconds | Standard Deviation 3.127 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | Uncorrected QT Interval , Day 3, Pre-dose | 0.67 milliseconds | Standard Deviation 17.55 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | QTcB, Day 3, Pre-dose | -8.00 milliseconds | Standard Deviation 17.428 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | RR interval, Day 3, Pre-dose | 40.56 milliseconds | Standard Deviation 131.342 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part B | QTcB, Follow-up | -4.89 milliseconds | Standard Deviation 11.185 |
Primary
Change From Baseline in ECG Parameters for Part C
Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time frame: Baseline (Day -1) and Day 7 (pre-dose) and follow-up (Day 23)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | QTcB, Follow-up | -22.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | QRS duration, Day 7 Pre-dose | -14.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | QTcF, Day 7, Pre-dose | -6.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | Uncorrected QT Interval , Day 7, Pre-dose | 10.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | QTcF, Follow-up | -11.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | RR interval, Day 7, Pre-dose | 115.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | QRS duration, Follow-up | -4.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | RR interval, Follow-up | 171.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | PR interval, Follow-up | -10.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | QTcB, Day 7, Pre-dose | -14.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | Uncorrected QT Interval , Follow-up | 12.00 milliseconds | — |
| Part A-GSK2646264 0.5% | Change From Baseline in ECG Parameters for Part C | PR interval, Day 7 Pre-dose | 10.00 milliseconds | — |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | Uncorrected QT Interval , Follow-up | -1.00 milliseconds | Standard Deviation 16.452 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | PR interval, Day 7 Pre-dose | 1.50 milliseconds | Standard Deviation 3 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | PR interval, Follow-up | -3.50 milliseconds | Standard Deviation 4.726 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | QRS duration, Day 7 Pre-dose | -1.00 milliseconds | Standard Deviation 1.155 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | QRS duration, Follow-up | 0.00 milliseconds | Standard Deviation 1.633 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | QTcB, Day 7, Pre-dose | -4.50 milliseconds | Standard Deviation 5.066 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | QTcB, Follow-up | 9.75 milliseconds | Standard Deviation 17.557 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | QTcF, Day 7, Pre-dose | -3.25 milliseconds | Standard Deviation 6.131 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | RR interval, Day 7, Pre-dose | 17.50 milliseconds | Standard Deviation 15.948 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | RR interval, Follow-up | -35.25 milliseconds | Standard Deviation 117.766 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | Uncorrected QT Interval , Day 7, Pre-dose | -1.00 milliseconds | Standard Deviation 7.394 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in ECG Parameters for Part C | QTcF, Follow-up | 5.75 milliseconds | Standard Deviation 12.92 |
Primary
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A
Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, corrected QT (QTc-Bazett \[QTcB\], QTC interval-Fredericia \[QTcF\]) intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day -1) and Day 4, and follow-up (Day 5 to Day 7)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | PR interval, Day 4 | -0.67 milliseconds | Standard Deviation 11.136 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | PR interval, Follow-up | 0.22 milliseconds | Standard Deviation 12.347 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QRS duration, Day 4 | -0.44 milliseconds | Standard Deviation 5.637 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QRS duration, Follow-up | -0.22 milliseconds | Standard Deviation 5.239 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QTcB, Day 4 | -6.11 milliseconds | Standard Deviation 14.252 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QTcB, Follow-up | -5.33 milliseconds | Standard Deviation 16.963 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QTcF, Follow-up | -8.00 milliseconds | Standard Deviation 13.829 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | RR interval, Day 4 | 82.89 milliseconds | Standard Deviation 174.628 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | RR interval, Follow-up | -40.11 milliseconds | Standard Deviation 114.704 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | Uncorrected QT Interval , Day 4 | 9.33 milliseconds | Standard Deviation 23.302 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | Uncorrected QT Interval , Follow-up | -12.89 milliseconds | Standard Deviation 20.028 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QTcF, Day 4 | -1.22 milliseconds | Standard Deviation 7.362 |
Primary
Change From Baseline in Electrocardiogram (ECG) Parameters for Part A
Triplicate 12-lead ECGs were obtained at screening and during the study single ECGs were taken. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, corrected QT (QTc-Bazett \[QTcB\], QTC interval-Fredericia\[QTcF\]) intervals, RR interval and uncorrected QT interval. Baseline was defined as assessment performed at Day -1. Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day -1) and Day 8 and follow-up (Day 9 to Day 11)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | PR interval, Day 8 | 7.75 milliseconds | Standard Deviation 17.678 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | PR interval, Follow-up | 4.00 milliseconds | Standard Deviation 18.237 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QRS duration, Day 8 | 0.25 milliseconds | Standard Deviation 3.615 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QRS duration, Follow-up | 3.25 milliseconds | Standard Deviation 4.132 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QTcB, Day 8 | -5.13 milliseconds | Standard Deviation 10.696 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QTcB, Follow-up | -1.75 milliseconds | Standard Deviation 16.211 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QTcF, Day 8 | -4.13 milliseconds | Standard Deviation 8.855 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | QTcF, Follow-up | -5.63 milliseconds | Standard Deviation 16.309 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | RR interval, Day 8 | 14.63 milliseconds | Standard Deviation 88.569 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | RR interval, Follow-up | -49.75 milliseconds | Standard Deviation 98.561 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | Uncorrected QT Interval , Day 8 | -2.00 milliseconds | Standard Deviation 15.856 |
| Part A-GSK2646264 0.5% | Change From Baseline in Electrocardiogram (ECG) Parameters for Part A | Uncorrected QT Interval , Follow-up | -13.00 milliseconds | Standard Deviation 24.727 |
Primary
Change From Baseline in Vital Sign Parameter Heart Rate for Part A
Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2, Day 3, Day 4 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 2 - Pre-dose | 0.2 Beats/minute | Standard Deviation 5.43 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 3 - Pre-dose | 0.9 Beats/minute | Standard Deviation 6.01 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 4 | 3.0 Beats/minute | Standard Deviation 7.12 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Follow-up | 10.4 Beats/minute | Standard Deviation 9.32 |
Primary
Change From Baseline in Vital Sign Parameter Heart Rate for Part A
Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 2 - Pre-dose | -2.1 Beats/minute | Standard Deviation 5.99 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 3 - Pre-dose | 1.0 Beats/minute | Standard Deviation 5.53 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 4 - Pre-dose | -0.8 Beats/minute | Standard Deviation 5.5 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 5 | -1.9 Beats/minute | Standard Deviation 3.91 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 6 | 1.0 Beats/minute | Standard Deviation 2.51 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 7 | 2.0 Beats/minute | Standard Deviation 4.07 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Day 8 | 3.9 Beats/minute | Standard Deviation 4.61 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part A | Follow-up | 8.0 Beats/minute | Standard Deviation 8.73 |
Primary
Change From Baseline in Vital Sign Parameter Heart Rate for Part B
Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 6 | 4.0 Beats/minute | Standard Deviation 4 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 12 | 16.0 Beats/minute | Standard Deviation 10.58 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 3 - Pre-dose | 10.0 Beats/minute | Standard Deviation 5.29 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 15 | 19.3 Beats/minute | Standard Deviation 11.02 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 9 | 14.0 Beats/minute | Standard Deviation 3.46 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Follow-up | 12.0 Beats/minute | Standard Deviation 13.86 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 2 - Pre-dose | 8.0 Beats/minute | Standard Deviation 6.93 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Follow-up | 2.0 Beats/minute | Standard Deviation 18.44 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 2 - Pre-dose | -1.1 Beats/minute | Standard Deviation 8.07 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 3 - Pre-dose | -0.9 Beats/minute | Standard Deviation 10.73 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 6 | 2.9 Beats/minute | Standard Deviation 16.1 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 9 | 2.6 Beats/minute | Standard Deviation 13.39 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 12 | 8.0 Beats/minute | Standard Deviation 14.7 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part B | Day 15 | 4.9 Beats/minute | Standard Deviation 17.41 |
Primary
Change From Baseline in Vital Sign Parameter Heart Rate for Part C
Vital sign heart rate was measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time frame: Baseline and (Day 1 pre-dose), Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15, follow-up (Day 23)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Day 15 | 20.0 Beats/minute | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Day 10 | 20.0 Beats/minute | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Follow-up | 8.0 Beats/minute | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Day 7 - Pre-dose | 4.0 Beats/minute | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Day 4 - Pre-dose | 16.0 Beats/minute | — |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Day 7 - Pre-dose | 2.3 Beats/minute | Standard Deviation 5.56 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Day 4 - Pre-dose | 4.8 Beats/minute | Standard Deviation 3.95 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Follow-up | 6.0 Beats/minute | Standard Deviation 6.73 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Day 10 | 8.5 Beats/minute | Standard Deviation 7.72 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameter Heart Rate for Part C | Day 15 | 14.3 Beats/minute | Standard Deviation 5.06 |
Primary
Change From Baseline in Vital Sign Parameters SBP and DBP for Part A
Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (pre-dose), Day 5, Day 6, Day 7, Day 8 and follow-up (Day 9 to Day 11)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | SBP, Day 2 - Pre-dose | 1.0 millimeters of mercury | Standard Deviation 12.41 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | SBP, Day 3 - Pre-dose | 1.8 millimeters of mercury | Standard Deviation 7.69 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | SBP, Day 6 | -3.9 millimeters of mercury | Standard Deviation 6.4 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | SBP, Day 7 | 0.3 millimeters of mercury | Standard Deviation 5.09 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | SBP, Day 8 | -4.4 millimeters of mercury | Standard Deviation 11.54 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | DBP, Day 5 | -3.8 millimeters of mercury | Standard Deviation 8.66 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | DBP, Day 8 | -3.6 millimeters of mercury | Standard Deviation 4.5 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | DBP, Follow-up | 2.0 millimeters of mercury | Standard Deviation 7.46 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | SBP, Day 4 - Pre-dose | 1.8 millimeters of mercury | Standard Deviation 9.27 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | SBP, Day 5 | -2.9 millimeters of mercury | Standard Deviation 6.83 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | SBP, Follow-up | 1.5 millimeters of mercury | Standard Deviation 4.41 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | DBP, Day 2 - Pre-dose | -4.0 millimeters of mercury | Standard Deviation 5.45 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | DBP, Day 3 - Pre-dose | -0.3 millimeters of mercury | Standard Deviation 8.68 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | DBP, Day 4 - Pre-dose | -0.6 millimeters of mercury | Standard Deviation 8.86 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | DBP, Day 6 | -5.0 millimeters of mercury | Standard Deviation 7.84 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part A | DBP, Day 7 | -1.1 millimeters of mercury | Standard Deviation 7.62 |
Primary
Change From Baseline in Vital Sign Parameters SBP and DBP for Part B
Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1(pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to Day 19)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 2 - Pre-dose | 8.3 millimeters of mercury | Standard Deviation 2.89 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 3 - Pre-dose | -1.7 millimeters of mercury | Standard Deviation 2.89 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 6 | 3.3 millimeters of mercury | Standard Deviation 2.89 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 9 | 5.0 millimeters of mercury | Standard Deviation 5 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 12 | 0.0 millimeters of mercury | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Follow-up | 0.0 millimeters of mercury | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 2 - Pre-dose | 1.7 millimeters of mercury | Standard Deviation 10.41 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 3 - Pre-dose | 0.0 millimeters of mercury | Standard Deviation 8.66 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 6 | 0.0 millimeters of mercury | Standard Deviation 10 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 9 | -3.3 millimeters of mercury | Standard Deviation 7.64 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 15 | 8.3 millimeters of mercury | Standard Deviation 2.89 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 12 | -3.3 millimeters of mercury | Standard Deviation 5.77 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 15 | -1.7 millimeters of mercury | Standard Deviation 11.55 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Follow-up | -1.7 millimeters of mercury | Standard Deviation 12.58 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 9 | 3.6 millimeters of mercury | Standard Deviation 13.6 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 2 - Pre-dose | 2.0 millimeters of mercury | Standard Deviation 6.6 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 3 - Pre-dose | 0.8 millimeters of mercury | Standard Deviation 11.03 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 15 | 2.4 millimeters of mercury | Standard Deviation 9.08 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 6 | -1.3 millimeters of mercury | Standard Deviation 14.82 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 6 | 2.4 millimeters of mercury | Standard Deviation 14.05 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 9 | -2.2 millimeters of mercury | Standard Deviation 10.64 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 12 | 3.0 millimeters of mercury | Standard Deviation 9.6 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 12 | 1.4 millimeters of mercury | Standard Deviation 14.05 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 15 | -6.7 millimeters of mercury | Standard Deviation 11.73 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Day 3 - Pre-dose | 0.6 millimeters of mercury | Standard Deviation 8.82 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | SBP, Follow-up | -3.3 millimeters of mercury | Standard Deviation 12.99 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Follow-up | 3.0 millimeters of mercury | Standard Deviation 13.77 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign Parameters SBP and DBP for Part B | DBP, Day 2 - Pre-dose | 2.4 millimeters of mercury | Standard Deviation 7.5 |
Primary
Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A
Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 2, Day 3, Day 4 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 2 (pre-dose), Day 3 (pre-dose), Day 4 and follow-up (Day 5 to Day 7)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | SBP, Day 2 - Pre-dose | -0.1 millimeters of mercury | Standard Deviation 11.21 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | SBP, Day 3 - Pre-dose | -0.9 millimeters of mercury | Standard Deviation 7.27 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | SBP, Day 4 | -1.1 millimeters of mercury | Standard Deviation 9.31 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | SBP, Follow-up | 4.1 millimeters of mercury | Standard Deviation 11.38 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | DBP, Day 2 - Pre-dose | -0.3 millimeters of mercury | Standard Deviation 4.5 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | DBP, Day 3 - Pre-dose | 0.6 millimeters of mercury | Standard Deviation 6.52 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | DBP, Day 4 | 2.2 millimeters of mercury | Standard Deviation 4.29 |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign Parameters Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part A | DBP, Follow-up | 4.2 millimeters of mercury | Standard Deviation 6.85 |
Primary
Change From Baseline in Vital Sign SBP and DBP for Part C
Vital signs SBP and DBP were measured in the semi-supine position after 10 minutes of rest. Assessments were performed at Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up. Baseline was defined as assessments performed at Day 1 (pre-dose). Change from Baseline was calculated as the post-dose visit value minus the Baseline value. NA indicates standard deviation could not be calculated as a single participant was analyzed.
Time frame: Baseline (Day 1 pre-dose) and Day 4 (pre-dose), Day 7 (pre-dose), Day 10, Day 15 and follow-up (Day 23)
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Follow-up | 0.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Day 15 | -10.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Day 15 | -10.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Day 4 - Pre-dose | -10.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Day 4 - Pre-dose | -10.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Day 10 | -10.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Day 7 - Pre-dose | -10.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Day 10 | -20.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Day 7 - Pre-dose | -10.0 millimeters of mercury | — |
| Part A-GSK2646264 0.5% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Follow-up | -10.0 millimeters of mercury | — |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Day 7 - Pre-dose | -4.8 millimeters of mercury | Standard Deviation 8.18 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Day 10 | 5.3 millimeters of mercury | Standard Deviation 15.06 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Day 15 | 12.3 millimeters of mercury | Standard Deviation 28.83 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Follow-up | 10.0 millimeters of mercury | Standard Deviation 18.55 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Day 4 - Pre-dose | -5.0 millimeters of mercury | Standard Deviation 9.13 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Day 7 - Pre-dose | -4.5 millimeters of mercury | Standard Deviation 17.6 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Day 15 | -1.0 millimeters of mercury | Standard Deviation 10.89 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Follow-up | 2.0 millimeters of mercury | Standard Deviation 2 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | SBP, Day 4 - Pre-dose | -5.5 millimeters of mercury | Standard Deviation 12.56 |
| Part B (10% BSA) GSK2646264 1% | Change From Baseline in Vital Sign SBP and DBP for Part C | DBP, Day 10 | -6.5 millimeters of mercury | Standard Deviation 3.7 |
Primary
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Safety population comprised of all participants who took at least one dose of study treatment.
Time frame: Up to Day 7
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A | AEs | 4 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) Part A | SAEs | 0 Participants |
Primary
Number of Participants With AEs and SAEs Defined by Severity Part A
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.
Time frame: Up to Day 11
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part A | Mild | 3 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part A | Moderate | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part A | Severe | 0 Participants |
Primary
Number of Participants With AEs and SAEs Defined by Severity Part A
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.
Time frame: Up to Day 7
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part A | Mild | 3 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part A | Moderate | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part A | Severe | 0 Participants |
Primary
Number of Participants With AEs and SAEs Defined by Severity Part B
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities. Data is presented according to the percentage BSA as it impacted safety
Time frame: Up to 19 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part B | Severe | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part B | Mild | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part B | Moderate | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part B | Severe | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part B | Mild | 2 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part B | Moderate | 1 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With AEs and SAEs Defined by Severity Part B | Moderate | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With AEs and SAEs Defined by Severity Part B | Mild | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With AEs and SAEs Defined by Severity Part B | Severe | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part B | Mild | 2 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part B | Severe | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part B | Moderate | 1 Participants |
Primary
Number of Participants With AEs and SAEs Defined by Severity Part C
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. AE and SAE were categorized as mild=an event that was easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities, moderate=an event that was sufficiently discomforting to interfere with normal everyday activities and severe=an event that prevented normal everyday activities.
Time frame: Up to 23 days
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part C | Mild | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part C | Severe | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Defined by Severity Part C | Moderate | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part C | Mild | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part C | Severe | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Defined by Severity Part C | Moderate | 0 Participants |
Primary
Number of Participants With AEs and SAEs Part A
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Time frame: Up to Day 11
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Part A | AEs | 4 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Part A | SAEs | 0 Participants |
Primary
Number of Participants With AEs and SAEs Part B
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant. Data is presented according to the percentage BSA as it impacted safety
Time frame: Up to Day 19
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Part B | AEs | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Part B | SAEs | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Part B | SAEs | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Part B | AEs | 3 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With AEs and SAEs Part B | AEs | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With AEs and SAEs Part B | SAEs | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Part B | SAEs | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Part B | AEs | 3 Participants |
Primary
Number of Participants With AEs and SAEs Part C
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.
Time frame: Up to Day 23
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Part C | AEs | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With AEs and SAEs Part C | SAEs | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Part C | AEs | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With AEs and SAEs Part C | SAEs | 0 Participants |
Primary
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A
Clinical chemistry parameters assessed were alanine amino transferase (ALT), albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride, creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/BUN). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.
Time frame: Day 5, Day 7 and follow up (Day 9 to Day 11)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A | Chloride, Day 5, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A | Chloride, Day 7, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A | Chloride, Follow-up, High, | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part A | GGT, Day 7, Low | 1 Participants |
Primary
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B
Clinical chemistry parameters assessed were ALT, albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride (low \<98 millimoles/liter and high \>106 millimoles/liter), creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/BUN (low \<2.9 and high \>7.1). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.
Time frame: Day 3 and follow up (Day 17 to Day 19)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | GGT, Follow-up, Low, n=3,9 | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Chloride, Follow up, Low,n=3,9 | 3 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Phosphorus, Day 3, Low, n=3,9 | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Urea/BUN, Day 3, Low, n=3,9 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Phosphorus, Follow-up, Low, n=3,9 | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Chloride, Follow-up, High, n=3,9 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Direct Bilirubin, Day 3, High, n=3,8 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Potassium, Day 3, High, n=3,9 | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Direct Bilirubin, Follow-up, High, n=3,9 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Potassium, Follow-up, Low, n=3,9 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Chloride, Day 3, Low, n=3,9 | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | GGT, Day 3, High, n=3,9 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Urea/BUN, Follow-up, High, n=3,8 | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Potassium, Day 3, Low, n=3,9 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Urea/BUN, Follow-up, High, n=3,8 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Direct Bilirubin, Day 3, High, n=3,8 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Chloride, Day 3, Low, n=3,9 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Chloride, Follow up, Low,n=3,9 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Direct Bilirubin, Follow-up, High, n=3,9 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | GGT, Day 3, High, n=3,9 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | GGT, Follow-up, Low, n=3,9 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Phosphorus, Day 3, Low, n=3,9 | 4 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Phosphorus, Follow-up, Low, n=3,9 | 3 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Potassium, Day 3, Low, n=3,9 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Potassium, Day 3, High, n=3,9 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Potassium, Follow-up, Low, n=3,9 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Urea/BUN, Day 3, Low, n=3,9 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part B | Chloride, Follow-up, High, n=3,9 | 1 Participants |
Primary
Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C
Clinical chemistry parameters assessed were ALT, albumin (low \<30 grams/liter), alkaline phosphatase, AST, calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride (low \<98 millimoles/liter and high \>106 millimoles/liter), creatinine (high \>159 micromoles/liter), direct bilirubin, GGT (low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein (low \<60 grams/liter and high \>78 grams/liter) and urea/BUN (low \<2.9 millimoles/liter and high \>7.1 millimoles/liter). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.
Time frame: Day 1, Day 7 and follow up (Day 23)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Total protein, Day 1, High, n=1,4 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Chloride, Day 7, Low, n=1,2 | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Phosphorus, Day 1, Low, n=1,4 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Urea/BUN, Day 1, Low, n=1,2 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Chloride, Follow-up, Low, n=1,3 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Urea/BUN, Day 1, Low, n=1,2 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Chloride, Follow-up, Low, n=1,3 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Total protein, Day 1, High, n=1,4 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Phosphorus, Day 1, Low, n=1,4 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Clinical Chemistry Data Outside the Range of PCI for Part C | Chloride, Day 7, Low, n=1,2 | 0 Participants |
Primary
Number of Participants With Clinical Chemistry Data Outside the Range of Potential Clinical Importance (PCI) for Part A
Clinical chemistry parameters assessed were alanine amino transferase (ALT), albumin (low \<30 grams/liter), alkaline phosphatase, aspartate aminotransferase (AST), calcium (low \<2 millimoles/liter and high \>2.75 millimoles/liter), chloride, creatinine (high \>159 micromoles/liter), direct bilirubin, gamma glutamyl transferase (GGT low \<8 units/liter and high \>78 units/liter), glucose (low \<3 millimoles/liter and high \>11.1 millimoles/liter), phosphorus (low 0.97 millimoles/liter and high 1.45 millimoles/liter), potassium (low \<3 millimoles/liter and high \>5.5 millimoles/liter), sodium (low \<130 millimoles/liter and high \>150 millimoles/liter), total bilirubin, total protein and urea/blood urea nitrogen (BUN). Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.
Time frame: Day 4 and follow up (Day 5 to Day 7)
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Clinical Chemistry Data Outside the Range of Potential Clinical Importance (PCI) for Part A | 1 Participants |
Primary
Number of Participants With Hematology Data Outside the Range of PCI for Part A
Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), mean corpuscle hemoglobin (MCH low \<28 picograms and high \>32 picograms), mean corpuscle hemoglobin concentration (MCHC low \<32 grams/liter and high \>36 grams/liter), mean corpuscle volume (MCV), monocytes (high \>0.208x 10\^9 cells/Liter), platelet count, red blood cell (RBC low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and white blood cell (WBC) count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.
Time frame: Day 4 and follow up (Day 5 to Day 7)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | MCH, Day 4, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Basophils, Day 4, High | 9 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Basophils, Follow-up, High | 9 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | MCH, Follow-up, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Monocytes, Day 4, High | 9 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Monocytes, Follow-up, High | 9 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Lymphocytes, Follow-up, Low | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | RBC count, Follow-up, Low | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Eosinophils, Day 4, High | 1 Participants |
Primary
Number of Participants With Hematology Data Outside the Range of PCI for Part A
Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), MCH (low \<28 picograms and high \>32 picograms), MCHC (low \<32 grams/liter and high \>36 grams/liter), MCV, monocytes (high \>0.208x10\^9 cells/Liter), platelet count, RBC count (low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils, WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.
Time frame: Day 5, Day 7 and follow up (Day 9 to Day 11)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | RBC count, Day 7, Low | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Basophils, Day 5, High | 7 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Basophils, Day 7, High | 8 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Basophils, Follow-up, High | 8 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | MCH, Follow-up, High | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | MCHC, Day 5, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | MCHC, Day 7, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Monocytes, Follow-up, High | 8 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Lymphocytes, Follow-up,Low | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Monocytes, Day 5, High | 8 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | Monocytes, Day 7, High | 8 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | RBC count, Day 5, Low | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part A | RBC count, Follow-up, Low | 1 Participants |
Primary
Number of Participants With Hematology Data Outside the Range of PCI for Part B
Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), MCH (low \<28 picograms and high \>32 picograms), MCHC (low \<32 grams/liter and high \>36 grams/liter), MCV, monocytes (high \>0.208x10\^9 cells/Liter), platelet count, RBC count (low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.
Time frame: Day 3 and follow up (Day 17 to 19)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Eosinophils, Day 3, High | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Basophils, Day 3, High | 3 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Monocytes, Day 3, High | 3 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Eosinophils, Follow-up, High | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Monocytes, Follow-up, High | 3 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | MCHC, Follow-up, Low | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | RBC count, Follow-up, Low | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Basophils, Follow-up, High | 3 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | RBC count, Follow-up, Low | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Basophils, Follow-up, High | 9 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Eosinophils, Day 3, High | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Eosinophils, Follow-up, High | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | MCHC, Follow-up, Low | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Basophils, Day 3, High | 9 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Monocytes, Day 3, High | 9 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part B | Monocytes, Follow-up, High | 9 Participants |
Primary
Number of Participants With Hematology Data Outside the Range of PCI for Part C
Hematology parameters assessed were basophils (high \>0.1x10\^9 cells/Liter), eosinophils (high \>0.44x 10\^9 cells/Liter), hematocrit, hemoglobin, lymphocytes (low \<0.8x10\^9 cells/Liter), MCH (low \<28 picograms and high \>32 picograms), MCHC low \<32 grams/liter and high \>36 grams/liter), MCV, monocytes (high \>0.208x10\^9 cells/Liter), platelet count, RBC count (low \<4.2x10\^6 cells/microliter and high 5.9x10\^6 cells/microliter) count, total neutrophils and WBC count. Values flagged as high and low of PCI for participants have been presented. Only categories with non-zero values have been presented.
Time frame: Day 1, Day 7 and follow up (Day 23)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | MCH, Day 7, Low | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Basophils, Day 7, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Basophils, Follow-up, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Monocytes, Day 7, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Monocytes, Follow-up, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | MCH, Day 1, Low | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | MCH, Follow-up, Low | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Monocytes, Day 1, High | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Basophils, Day 1, High | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Basophils, Follow-up, High | 2 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Basophils, Day 1, High | 3 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | MCH, Day 1, Low | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Basophils, Day 7, High | 3 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | MCH, Day 7, Low | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Monocytes, Day 1, High | 4 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Monocytes, Follow-up, High | 4 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | Monocytes, Day 7, High | 4 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Hematology Data Outside the Range of PCI for Part C | MCH, Follow-up, Low | 0 Participants |
Primary
Number of Participants With Tolerability Assessment for Part A
Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.
Time frame: Up to Day 4
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, F | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 1 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 2 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 3 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 4 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 5 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 6 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 7 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, Z | 9 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, A | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, B | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, C | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, G | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, H | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 0 | 9 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, H | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, Z | 9 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, G | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, F | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 2 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 1 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, C | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 5 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, B | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 6 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 3 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, A | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 7 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 4 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 0 | 8 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 3 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 4 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, G | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 5 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 6 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 7 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, Z | 8 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, H | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, A | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, B | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, C | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 0 | 6 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, F | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 1 | 2 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 2 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, Z | 8 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 7 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 2 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 0 | 8 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 6 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, G | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 4 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 1 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, F | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 5 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, B | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, H | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, A | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal dermal response, Grade 3 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part A | Maximal other dermal effects, C | 0 Participants |
Primary
Number of Participants With Tolerability Assessment for Part B
Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.
Time frame: Up to Day 3
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 4 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 1 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 2 | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 0 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 7 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, Z | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, A | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, B | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, C | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, G | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, H | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 3 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 5 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 6 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, F | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, H | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, A | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 4 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, F | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, C | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, B | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 0 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, G | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 7 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 6 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 2 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 5 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, Z | 2 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 3 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 1 | 1 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, A | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 5 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 6 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, F | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 7 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 4 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, Z | 2 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, B | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, C | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, G | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, H | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 0 | 2 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 1 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 2 | 0 Participants |
| Part B (3.5% BSA)-Placebo | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 3 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 2 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 6 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 0 | 6 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, F | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, Z | 6 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 4 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 1 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, H | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 5 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 7 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, C | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, A | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, B | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal dermal response, Grade 3 | 0 Participants |
| Part B (3.5% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part B | Maximal other dermal effects, G | 0 Participants |
Primary
Number of Participants With Tolerability Assessment for Part C
Tolerability was assessed with the skin irritation scoring system of study, where the score consists of a numeric score according to the dermal response scoring as follows 0=no evidence of irritation, 1=minimal erythema, barely perceptible (pink), 2=moderate erythema (definite redness), 3=strong erythema (intense redness), 4=definite edema, 5=erythema, edema, and papules, 6=vesicular eruption, 7=strong reaction spreading beyond test site, and a letter according to the other effects scoring, Z=no other effect, A=slight glazed appearance, B=marked glazing, C=glazing with peeling and cracking, F=glazing with fissures, G=film of dried serous exudate covering all or part of the patch site, H=small petechial erosions and/or scabs. For each skin assessment, letter grade will be converted to numeric values as below: A=0, Z=0, B=1, C=2, F=3, G=3, H=3. A combined score for each participant was calculated by adding all numeric and letter scores. A maximum score of 3 was allowed.
Time frame: Up to Day 7
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 4 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 1 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, A | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 5 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, B | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 3 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, C | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, F | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 6 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, G | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 2 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, H | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 7 | 0 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, Z | 1 Participants |
| Part A-GSK2646264 0.5% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 0 | 1 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, C | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 0 | 4 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 1 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 2 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 3 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 4 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 5 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 6 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal dermal response, Grade 7 | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, Z | 4 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, A | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, B | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, F | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, G | 0 Participants |
| Part B (10% BSA) GSK2646264 1% | Number of Participants With Tolerability Assessment for Part C | Maximal other dermal effects, H | 0 Participants |
Secondary
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software. NA indicated data was not collected due to insufficient participants with data.
Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A-GSK2646264 0.5% | Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A | NA Hours*nanograms/milliliter |
Secondary
Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4
Population: PK Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of GSK2646264 for Part A | 97.8835 Hours*nanograms/milliliter | Geometric Coefficient of Variation 37 |
Secondary
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-infinity) was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3
Population: PK Population. Only those participants available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B | Day 3 | 844.3091 Hours*nanograms/milliliter | Geometric Coefficient of Variation 22 |
| Part B (10% BSA) GSK2646264 1% | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B | Day 3 | 390.7973 Hours*nanograms/milliliter | Geometric Coefficient of Variation 109 |
| Unknown | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B | Day 1 | — Hours*nanograms/milliliter | — |
| Unknown | Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of GSK2646264 for Part B | Day 2 | — Hours*nanograms/milliliter | — |
Secondary
Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-T) was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3
Population: PK Population. Only those participants with data available at the specified time points were analyzed represented by n=x in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A | Day 1, n=3 | 0.5411 Hours*nanograms/milliliter | Geometric Coefficient of Variation 45 |
| Part A-GSK2646264 0.5% | Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A | Day 2,n=9 | 3.1462 Hours*nanograms/milliliter | Geometric Coefficient of Variation 60 |
| Part A-GSK2646264 0.5% | Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of GSK2646264 for Part A | Day 3, n=9 | 15.2614 Hours*nanograms/milliliter | Geometric Coefficient of Variation 66 |
Secondary
AUC (0-24) of GSK2646264 for Part B
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-24) was determined using the currently approved and validated software. NA indicates that geometric coefficient of variation could not be computed for Part B (3.5% BSA) GSK2646264 1% as a single participant was analyzed on Day 2.
Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 (Day 4)
Population: PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | AUC (0-24) of GSK2646264 for Part B | Day 3, n=3, 6 | 166.6914 Hours*nanograms/milliliter | Geometric Coefficient of Variation 14 |
| Part B (10% BSA) GSK2646264 1% | AUC (0-24) of GSK2646264 for Part B | Day 2, n=0, 1 | 34.4377 Hours*nanograms/milliliter | — |
| Part B (10% BSA) GSK2646264 1% | AUC (0-24) of GSK2646264 for Part B | Day 3, n=3, 6 | 68.2224 Hours*nanograms/milliliter | Geometric Coefficient of Variation 120 |
| Unknown | AUC (0-24) of GSK2646264 for Part B | Day 1, n=0, 0 | — Hours*nanograms/milliliter | — |
Secondary
AUC (0-t) of GSK2646264 for Part A
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-T) was determined using the currently approved and validated software.
Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | AUC (0-t) of GSK2646264 for Part A | Day 1 | 8.6870 Hours*nanograms/milliliter | Geometric Coefficient of Variation 86 |
| Part A-GSK2646264 0.5% | AUC (0-t) of GSK2646264 for Part A | Day 2 | 31.0600 Hours*nanograms/milliliter | Geometric Coefficient of Variation 53 |
| Part A-GSK2646264 0.5% | AUC (0-t) of GSK2646264 for Part A | Day 3 | 60.2293 Hours*nanograms/milliliter | Geometric Coefficient of Variation 40 |
| Part A-GSK2646264 0.5% | AUC (0-t) of GSK2646264 for Part A | Day 4 | 382.4520 Hours*nanograms/milliliter | Geometric Coefficient of Variation 40 |
Secondary
AUC [0-t] of GSK2646264 for Part B
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the AUC (0-t) was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | AUC [0-t] of GSK2646264 for Part B | Day 2 | 100.6152 Hours*nanograms/milliliter | Geometric Coefficient of Variation 18 |
| Part A-GSK2646264 0.5% | AUC [0-t] of GSK2646264 for Part B | Day 3 | 825.1809 Hours*nanograms/milliliter | Geometric Coefficient of Variation 22 |
| Part A-GSK2646264 0.5% | AUC [0-t] of GSK2646264 for Part B | Day 1 | 40.5235 Hours*nanograms/milliliter | Geometric Coefficient of Variation 92 |
| Part B (10% BSA) GSK2646264 1% | AUC [0-t] of GSK2646264 for Part B | Day 1 | 18.7840 Hours*nanograms/milliliter | Geometric Coefficient of Variation 101 |
| Part B (10% BSA) GSK2646264 1% | AUC [0-t] of GSK2646264 for Part B | Day 2 | 46.5654 Hours*nanograms/milliliter | Geometric Coefficient of Variation 96 |
| Part B (10% BSA) GSK2646264 1% | AUC [0-t] of GSK2646264 for Part B | Day 3 | 379.8602 Hours*nanograms/milliliter | Geometric Coefficient of Variation 109 |
Secondary
Cmax of GSK2646264 for Part A
Blood samples were collected at the indicated time points to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.
Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Cmax of GSK2646264 for Part A | Day 1 | 0.72391 Nanograms/milliliter | Geometric Coefficient of Variation 72 |
| Part A-GSK2646264 0.5% | Cmax of GSK2646264 for Part A | Day 2 | 1.96715 Nanograms/milliliter | Geometric Coefficient of Variation 43 |
| Part A-GSK2646264 0.5% | Cmax of GSK2646264 for Part A | Day 3 | 3.28320 Nanograms/milliliter | Geometric Coefficient of Variation 34 |
| Part A-GSK2646264 0.5% | Cmax of GSK2646264 for Part A | Day 4 | 5.22144 Nanograms/milliliter | Geometric Coefficient of Variation 41 |
Secondary
Cmax of GSK2646264 for Part B
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3 (Day 4)
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Cmax of GSK2646264 for Part B | Day 1 | 2.71563 Nanograms/milliliter | Geometric Coefficient of Variation 69 |
| Part A-GSK2646264 0.5% | Cmax of GSK2646264 for Part B | Day 2 | 5.14144 Nanograms/milliliter | Geometric Coefficient of Variation 6 |
| Part A-GSK2646264 0.5% | Cmax of GSK2646264 for Part B | Day 3 | 7.51684 Nanograms/milliliter | Geometric Coefficient of Variation 8 |
| Part B (10% BSA) GSK2646264 1% | Cmax of GSK2646264 for Part B | Day 1 | 1.30673 Nanograms/milliliter | Geometric Coefficient of Variation 109 |
| Part B (10% BSA) GSK2646264 1% | Cmax of GSK2646264 for Part B | Day 2 | 2.41207 Nanograms/milliliter | Geometric Coefficient of Variation 92 |
| Part B (10% BSA) GSK2646264 1% | Cmax of GSK2646264 for Part B | Day 3 | 2.89771 Nanograms/milliliter | Geometric Coefficient of Variation 120 |
Secondary
Cmax of GSK2646264 for Part C
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.
Time frame: Pre dose and 4 hours post-dose on Days 1, 4 and 7
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Cmax of GSK2646264 for Part C | 1.85336 Nanograms/milliliter | Geometric Coefficient of Variation 185 |
Secondary
Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the Cmax was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3
Population: PK Population. Only those participants with data available at the specified time points were analyzed represented by n=x in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A | Day 1, n=3 | 0.07360 Nanograms/milliliter | Geometric Coefficient of Variation 34 |
| Part A-GSK2646264 0.5% | Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A | Day 2, n=9 | 0.25084 Nanograms/milliliter | Geometric Coefficient of Variation 69 |
| Part A-GSK2646264 0.5% | Maximum Plasma Concentration (Cmax) of GSK2646264 for Part A | Day 3,n=9 | 0.90382 Nanograms/milliliter | Geometric Coefficient of Variation 69 |
Secondary
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A
Blood samples were collected to assess the plasma concentration of GSK2646264 for Part A on Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours), Day 3 (1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours). The actual date and time of each blood sample collection was recorded.
Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours), Day 3 (1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, Pre-dose | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 1 hour | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 2 hours | 0.02780 nanograms/milliliter | Standard Deviation 0.0278 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 4 hours | 0.19470 nanograms/milliliter | Standard Deviation 0.1947 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 8 hours | 0.31849 nanograms/milliliter | Standard Deviation 0.31849 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 12 hours | 0.49735 nanograms/milliliter | Standard Deviation 0.49735 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 24 hours | 0.86538 nanograms/milliliter | Standard Deviation 0.86538 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 1 hour | 0.82164 nanograms/milliliter | Standard Deviation 0.82164 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 2 hours | 0.91896 nanograms/milliliter | Standard Deviation 0.91896 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 4 hours | 1.10081 nanograms/milliliter | Standard Deviation 1.10081 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 8 hours | 1.18935 nanograms/milliliter | Standard Deviation 1.18935 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 12 hours | 1.44756 nanograms/milliliter | Standard Deviation 1.44756 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 24 hours | 2.11824 nanograms/milliliter | Standard Deviation 2.11824 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 1 hour | 2.15994 nanograms/milliliter | Standard Deviation 2.15994 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 2 hours | 2.17775 nanograms/milliliter | Standard Deviation 2.17775 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 4 hours | 2.39909 nanograms/milliliter | Standard Deviation 2.39909 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 8 hours | 2.30511 nanograms/milliliter | Standard Deviation 2.30511 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 12 hours | 2.72968 nanograms/milliliter | Standard Deviation 2.72968 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 24 hours | 3.40905 nanograms/milliliter | Standard Deviation 3.40905 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 4, 1 hour | 3.64494 nanograms/milliliter | Standard Deviation 3.64494 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 4, 2 hours | 3.76981 nanograms/milliliter | Standard Deviation 3.76981 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 4, 4 hours | 3.99425 nanograms/milliliter | Standard Deviation 3.99425 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 4, 8 hours | 3.88128 nanograms/milliliter | Standard Deviation 3.88128 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 4, 12 hours | 4.13984 nanograms/milliliter | Standard Deviation 4.13984 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 4, 24 hours | 5.35715 nanograms/milliliter | Standard Deviation 5.35715 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 5, 30 hours | 4.98988 nanograms/milliliter | Standard Deviation 1.807766 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 5, 36 hours | 4.63755 nanograms/milliliter | Standard Deviation 1.62907 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 6, 48 hours | 4.92234 nanograms/milliliter | Standard Deviation 1.690833 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 6, 54 hours | 4.44403 nanograms/milliliter | Standard Deviation 1.834524 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 6, 60 hours | 4.04828 nanograms/milliliter | Standard Deviation 1.646939 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 7, 72 hours | 4.02665 nanograms/milliliter | Standard Deviation 1.592538 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 7, 78 hours | 3.76244 nanograms/milliliter | Standard Deviation 1.751219 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 7, 84 hours | 3.45551 nanograms/milliliter | Standard Deviation 1.52289 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 8, 96 hours | 3.30003 nanograms/milliliter | Standard Deviation 1.364104 |
Secondary
Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A
Blood samples were collected to assess the plasma concentration of GSK2646264 for Part A on Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours) and Day 3 (1,2,4,8,12,24 hours). The actual date and time of each blood sample collection was recorded. PK Population comprised of all randomized participants of the Safety Population for whom a pharmacokinetic sample was obtained and analyzed.
Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (1,2,4,8,12,24 hours) and Day 3 (1,2,4,8,12,24 hours)
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 8 hours | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 12 hours | 0.00708 nanograms/milliliter | Standard Deviation 0.021233 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 24 hours | 0.02457 nanograms/milliliter | Standard Deviation 0.039577 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 1 hour | 0.00600 nanograms/milliliter | Standard Deviation 0.018 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 2 hours | 0.02524 nanograms/milliliter | Standard Deviation 0.038068 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 4 hours | 0.07198 nanograms/milliliter | Standard Deviation 0.064932 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 8 hours | 0.20567 nanograms/milliliter | Standard Deviation 0.340281 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 12 hours | 0.16524 nanograms/milliliter | Standard Deviation 0.11768 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 2, 24 hours | 0.23991 nanograms/milliliter | Standard Deviation 0.092812 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 1 hour | 0.25198 nanograms/milliliter | Standard Deviation 0.105292 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 2 hours | 0.36364 nanograms/milliliter | Standard Deviation 0.197974 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 4 hours | 0.50156 nanograms/milliliter | Standard Deviation 0.239403 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 8 hours | 0.67546 nanograms/milliliter | Standard Deviation 0.396632 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 12 hours | 0.81486 nanograms/milliliter | Standard Deviation 0.463918 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 3, 24 hours | 1.03606 nanograms/milliliter | Standard Deviation 0.601077 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, Pre-dose | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 1 hour | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 2 hours | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 Pharmacokinetic (PK) Concentrations for Part A | Day 1, 4 hours | 0.00000 nanograms/milliliter | Standard Deviation 0 |
Secondary
Plasma GSK2646264 PK Concentrations for Part B
Blood samples were collected to assess the plasma concentration of GSK2646264 for Part B on Day 1 (Pre-dose,1,4,8,12,24 hours), Day 2 (1,4,8,12,24 hours), Day 3 (1,4,8,12,24 hours), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to 19). The actual date and time of each blood sample collection was recorded.
Time frame: Day 1 (Pre-dose,1,4,8,12,24 hours), Day 2 (1,4,8,12,24 hours), Day 3 (1,4,8,12,24 hours), Day 6, Day 9, Day 12, Day 15 and follow-up (Day 17 to 19)
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 4 hours | 3.63953 nanograms/milliliter | Standard Deviation 1.603219 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 24 hours | 8.84147 nanograms/milliliter | Standard Deviation 1.665464 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 8 hours | 2.22747 nanograms/milliliter | Standard Deviation 1.658949 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 6 | 3.54063 nanograms/milliliter | Standard Deviation 0.611174 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 12 hours | 4.76710 nanograms/milliliter | Standard Deviation 0.642243 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 9 | 1.89157 nanograms/milliliter | Standard Deviation 0.453369 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 24 hours | 3.06623 nanograms/milliliter | Standard Deviation 1.944608 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 12 | 0.82347 nanograms/milliliter | Standard Deviation 0.545903 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 4 hours | 0.61280 nanograms/milliliter | Standard Deviation 0.640458 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 15 | 0.42230 nanograms/milliliter | Standard Deviation 0.195058 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 4 hours | 6.38943 nanograms/milliliter | Standard Deviation 1.58536 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Follow-up | 0.22513 nanograms/milliliter | Standard Deviation 0.129284 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 1 hour | 3.02890 nanograms/milliliter | Standard Deviation 1.739913 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 12 hours | 2.72833 nanograms/milliliter | Standard Deviation 2.378997 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 8 hours | 6.35937 nanograms/milliliter | Standard Deviation 1.256342 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, Pre-dose | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 1 hour | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 8 hours | 4.01943 nanograms/milliliter | Standard Deviation 1.338776 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 24 hours | 5.04110 nanograms/milliliter | Standard Deviation 0.124156 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 12 hours | 6.73903 nanograms/milliliter | Standard Deviation 1.011669 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 1 hour | 5.15953 nanograms/milliliter | Standard Deviation 0.564893 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 12 hours | 1.51255 nanograms/milliliter | Standard Deviation 1.018452 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, Pre-dose | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 1 hour | 0.01083 nanograms/milliliter | Standard Deviation 0.026536 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 4 hours | 0.21290 nanograms/milliliter | Standard Deviation 0.236751 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 24 hours | 1.44370 nanograms/milliliter | Standard Deviation 0.845724 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 1 hour | 1.63247 nanograms/milliliter | Standard Deviation 0.903514 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 8 hours | 2.28577 nanograms/milliliter | Standard Deviation 1.202992 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 12 hours | 2.57673 nanograms/milliliter | Standard Deviation 1.451027 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 1 hour | 3.09353 nanograms/milliliter | Standard Deviation 1.715172 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 4 hours | 3.38355 nanograms/milliliter | Standard Deviation 1.765959 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 8 hours | 3.30380 nanograms/milliliter | Standard Deviation 1.694633 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 12 hours | 3.60315 nanograms/milliliter | Standard Deviation 2.00484 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 3, 24 hours | 4.29153 nanograms/milliliter | Standard Deviation 2.451293 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 6 | 2.14953 nanograms/milliliter | Standard Deviation 1.053739 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 9 | 1.00005 nanograms/milliliter | Standard Deviation 0.572714 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 12 | 0.57632 nanograms/milliliter | Standard Deviation 0.320586 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 15 | 0.28658 nanograms/milliliter | Standard Deviation 0.232548 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Follow-up | 0.12982 nanograms/milliliter | Standard Deviation 0.10535 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 1, 8 hours | 0.67952 nanograms/milliliter | Standard Deviation 0.529431 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 4 hours | 1.86712 nanograms/milliliter | Standard Deviation 0.891829 |
| Part B (10% BSA) GSK2646264 1% | Plasma GSK2646264 PK Concentrations for Part B | Day 2, 24 hours | 2.90163 nanograms/milliliter | Standard Deviation 1.598613 |
Secondary
Plasma GSK2646264 PK Concentrations for Part C
Blood samples were collected to assess the plasma concentration of GSK2646264 for Part C on Day 1 (Pre-dose,1 and 4 hours), Day 4 (Pre-dose and 4 hours), Day 7 (Pre-dose and 4 hours), Day 10, Day 15 and follow-up. The actual date and time of each blood sample collection was recorded.
Time frame: Day 1 (Pre-dose,1 and 4 hours), Day 4 (Pre-dose and 4 hours), Day 7 (Pre-dose and 4 hours), Day 10, Day 15 and follow-up (Day 23)
Population: PK Population. Only those participants with data available at the specified time points were analyzed (represented by n=x in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Day 1, Pre-dose, n=3 | 0.00000 nanograms/milliliter | Standard Deviation 0 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Day 1, 4 hours, n=4 | 0.18048 nanograms/milliliter | Standard Deviation 0.12367 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Day 4, Pre-dose, n=3 | 1.22397 nanograms/milliliter | Standard Deviation 0.963854 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Day 4, 4 hours, n=3 | 1.37440 nanograms/milliliter | Standard Deviation 0.96182 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Day 7, Pre-dose, n=4 | 2.33635 nanograms/milliliter | Standard Deviation 2.342202 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Day 7, 4 hours, n=4 | 2.77940 nanograms/milliliter | Standard Deviation 2.275138 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Day 10,n=4 | 2.13075 nanograms/milliliter | Standard Deviation 1.830816 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Day 15,n=4 | 0.91718 nanograms/milliliter | Standard Deviation 0.895466 |
| Part A-GSK2646264 0.5% | Plasma GSK2646264 PK Concentrations for Part C | Follow-up, n=4 | 0.44233 nanograms/milliliter | Standard Deviation 0.34981 |
Secondary
t1/2 of GSK2646264 for Part A
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data.
Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose at Day 5 (30 and 36 hours), Day 6 (48,54 and 60 hours), Day 7 (72,78 and 84 hours) and Day 8 (96 hours)
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A-GSK2646264 0.5% | t1/2 of GSK2646264 for Part A | NA hours |
Secondary
t1/2 of GSK2646264 for Part C
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated data was not collected due to insufficient number of participants with data to calculate half life.
Time frame: Pre dose and 4 hours post-dose on Days 1, 4 and 7
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A-GSK2646264 0.5% | t1/2 of GSK2646264 for Part C | NA hours |
Secondary
Terminal Half-life (t1/2) of GSK2646264 for Part A
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software. NA indicated t1/2 could not be calculated as we need at least 3 time points after Cmax within the same participant and this criteria could not be fulfilled due to lack of available data.
Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2,3 and 4
Population: PK Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A-GSK2646264 0.5% | Terminal Half-life (t1/2) of GSK2646264 for Part A | NA hours |
Secondary
Terminal Half-life (t1/2) of GSK2646264 for Part B
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the t1/2 was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3
Population: PK Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Terminal Half-life (t1/2) of GSK2646264 for Part B | Day 3 | 59.69 hours | Geometric Coefficient of Variation 4.433 |
| Part B (10% BSA) GSK2646264 1% | Terminal Half-life (t1/2) of GSK2646264 for Part B | Day 3 | 64.01 hours | Geometric Coefficient of Variation 11.22 |
| Unknown | Terminal Half-life (t1/2) of GSK2646264 for Part B | Day 1 | — hours | — |
| Unknown | Terminal Half-life (t1/2) of GSK2646264 for Part B | Day 2 | — hours | — |
Secondary
Time to Cmax (Tmax) of GSK2646264 for Part A
Blood samples were collected at the indicated time points to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 and 24 hours post-dose on Days 1,2 and Day 3
Population: PK Population. Only those participants with data available at the specified time points were analyzed represented by n=x in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Time to Cmax (Tmax) of GSK2646264 for Part A | Day 1, n=3 | 19.60 hours | Standard Deviation 6.585 |
| Part A-GSK2646264 0.5% | Time to Cmax (Tmax) of GSK2646264 for Part A | Day 2, n=9 | 21.52 hours | Standard Deviation 5.074 |
| Part A-GSK2646264 0.5% | Time to Cmax (Tmax) of GSK2646264 for Part A | Day 3,n=9 | 20.32 hours | Standard Deviation 7.267 |
Secondary
Tmax of GSK2646264 for Part A
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.
Time frame: Day 1 (Pre-dose,1,2,4,8,12,24 hours), Day 2 (Pre-dose,1,2,4,8,12,24 hours), Day 3 (Pre-dose,1,2,4,8,12,24 hours) and Day 4 post-dose
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Tmax of GSK2646264 for Part A | Day 1 | 23.85 hours | Standard Deviation 0.053 |
| Part A-GSK2646264 0.5% | Tmax of GSK2646264 for Part A | Day 2 | 23.83 hours | Standard Deviation 0.046 |
| Part A-GSK2646264 0.5% | Tmax of GSK2646264 for Part A | Day 3 | 22.29 hours | Standard Deviation 4.158 |
| Part A-GSK2646264 0.5% | Tmax of GSK2646264 for Part A | Day 4 | 28.99 hours | Standard Deviation 14.18 |
Secondary
Tmax of GSK2646264 for Part B
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.
Time frame: Pre dose, 1 ,2, 4, 8, 12 hours post-dose on Days 1,2,3 and 24 hours post last dose on Day 3
Population: PK Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-GSK2646264 0.5% | Tmax of GSK2646264 for Part B | Day 2 | 16.93 hours | Standard Deviation 23.5 |
| Part A-GSK2646264 0.5% | Tmax of GSK2646264 for Part B | Day 3 | 13.33 hours | Standard Deviation 24 |
| Part A-GSK2646264 0.5% | Tmax of GSK2646264 for Part B | Day 1 | 19.67 hours | Standard Deviation 23.6 |
| Part B (10% BSA) GSK2646264 1% | Tmax of GSK2646264 for Part B | Day 1 | 17.85 hours | Standard Deviation 6.373 |
| Part B (10% BSA) GSK2646264 1% | Tmax of GSK2646264 for Part B | Day 2 | 21.13 hours | Standard Deviation 6.436 |
| Part B (10% BSA) GSK2646264 1% | Tmax of GSK2646264 for Part B | Day 3 | 12.62 hours | Standard Deviation 6.378 |
Secondary
Tmax of GSK2646264 for Part C
Blood samples were collected at the indicated time point to investigate the PK profile of GSK264624. From the GSK2646264 concentration-time data, the tmax was determined using the currently approved and validated software.
Time frame: Pre dose and 4 hours post-dose on Days 1, 4 and 7
Population: PK Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A-GSK2646264 0.5% | Tmax of GSK2646264 for Part C | 4.10 hours | Standard Deviation 0.082 |