Cachexia
Conditions
Keywords
GSK2881078, COPD, muscle weakness, post-menopausal, selective androgen receptor modulator
Brief summary
Impaired physical function and muscle dysfunction are a major consequence of COPD, which may be associated with increased mortality, poor quality of life and increased health care use. This is a randomized, placebo-controlled, double-blind, parallel group study to evaluate the safety and tolerability of GSK2881078, an SARM over 13 weeks of dosing in older male subjects and post-menopausal female subjects with COPD and muscle weakness. This study will also assess the effect of GSK2881078 on physical strength and function after 13 weeks of treatment. Approximately 100 subjects with COPD and muscle weakness will be randomized into two cohorts of 50 male subjects and 50 female subjects. Within each cohort, subjects will be randomized to receive GSK2881078 or placebo in a ratio of 1:1. All subjects will participate in a standardized home exercise program, which will consist of daily walking, along with several resistance or weight-bearing exercises, such as bicep curls, upright rows, step ups and a sit-to-stand maneuver. The study will consist of a screening/Baseline period of up to 30 days, a 13-week treatment period and a post-treatment follow-up period of 6 weeks.
Interventions
DRUGGSK2881078
GSK2881078 will be available as capsules for oral administration. GSK2881078 will be administered once daily by the oral route at a dose of 1 mg and 2mg to post-menopausal female subjects and male subjects, respectively.
DRUGMatching Placebo
Subjects will be administered two capsules of GSK2881078 matching placebo once daily by the oral route.
Sponsors
Parexel
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Study treatment will consist of two dosing cohorts: Cohort 1 will comprise of male subjects randomized to receive either placebo or 2 milligrams (mg) of GSK2881078 and Cohort 2 will comprise of post-menopausal female subjects randomized to receive either placebo or 1 mg of GSK2881078.
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subject must be 50 to 75 years of age inclusive, at the time of signing the informed consent. * Male and/or female subjects will be included. a) A male subject with a partner who is a woman of child bearing potential (WOCPB) must agree to use contraception during the treatment period and until at least 5 half-lives of study medication have passed after the last ingested dose \[125 days, corresponding to time needed to eliminate study treatment for both genotoxic and teratogenic study treatments plus an additional 90 days (a spermatogenesis cycle) for study treatments with genotoxic potential\] after the last dose of study treatment and refrain from donating sperm during this period. b) A female subject is eligible to participate if she is post-menopausal and not a WOCBP. * Confirmed diagnosis of COPD in accordance with the American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria with a post-bronchodilator FEV1/forced vital capacity (FVC) \<0.70 and 30% \<= FEV1% predicted \<=65% of predicted normal value calculated at Screen using the Quanjer reference equation. * SPPB with ALL of the following: Timed chair stand score \>=1 and \<=3; No score of 0 on any component of the SPPB (that is, gait speed, balance, or timed chair stand). * Body Mass Index (BMI) within the range 18-32 kilogram per meter square (kg/m\^2) (inclusive), where BMI = (weight in kg)/(height in meters)\^2 * Current smokers or former smokers with a cigarette smoking history of \>=10 pack years (1 pack year =20 cigarettes smoked per day for 1 year or equivalent). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Baseline. * Subjects must be able to read and write in the language used for the provided electronic diary and be able to operate an electronic device to a level that allows them to complete an electronic diary on a daily basis. * Subjects participating in a structured exercise program must be willing to convert their current exercise program to the home exercise program used in this study. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.
Exclusion criteria
* Subjects with a history of myocardial infarction, angina, congestive heart failure exacerbation, hospitalization for cardiac etiology, stroke or transient ischemic attack in the past 12 months. * Neurologic, musculoskeletal, osteoarthritis, or any other condition that in the opinion of the investigator limits subject's ability to complete study physical assessments. * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * Subjects with a history of cholecystectomy. * Subjects with a history of malignancy that is not in complete remission for at least 2 years or 1 year for non-melanoma skin carcinoma. * Subjects with a family history of early onset prostate cancer or familial prostate cancer (multiple family members). * Diseases known to cause malabsorption of protein or energy, such as inflammatory bowel disease, celiac disease, pancreatic insufficiency, etc. * Current or planned administration of cholestyramine or strong oral or injectable cytochrome P-450 isoenzyme 3A4 (CYP3A4) inducers. * Current or planned use of any prescription drugs known to affect muscle mass, including androgen supplements, anti-androgens (such as luteinizing hormone-releasing hormone \[LHRH\] agonists), anti-estrogens (tamoxifen, etc.), recombinant growth hormone, megesterol, etc. * Use of oral steroids concurrently or within 4 weeks preceding the screening visit. * The subject has participated in a clinical trial and has received an investigational product within the following time-period prior to randomization in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * Subjects with values outside the specified ranges for the following Key Clinical Laboratory Tests must be excluded from the study: a) Renal function: Glomerular Filtration Rate (GFR) \<30 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2). Subjects receiving dialysis are excluded from this study. b) Metabolic-glycated hemoglobin (HbA1c) \>7.5%. c) ALT \>2 times upper limit of normal (ULN) and bilirubin \>1.5 times ULN (isolated bilirubin \>1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). d) Hematology - Hemoglobin \<10.0 grams per deciliter (g/dL) at screening. e) Prostate Specific Antigen (PSA) \>4.0 nanograms per milliliter (ng/mL). * Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. * QT interval corrected for heart rate by Bazett's formula (QTcB) or QT interval corrected for heart rate by Fridericia's formula (QTcF) \>450 milliseconds (msec) or QT interval corrected for heart rate (QTc) \>480 msec in subjects with Bundle Branch Block based on a single ECG. * A positive test for human immunodeficiency virus (HIV) antibody. * More than two moderate/severe COPD exacerbations within the past year. Exacerbation is defined as worsening of two or more of the following major symptoms: dyspnea, sputum volume, sputum purulence OR worsening of any one major symptom together with at least one of the following additional symptoms: sore throat, colds (nasal discharge and/or nasal congestion), fever \>37.5 degree Celsius without any explained cause, increased cough, increased wheeze. A moderate exacerbation is defined as an exacerbation that requires treatment with antibiotics and/or oral steroids. A severe exacerbation is defined as an event that is additionally associated with hospitalization or emergency room visit. * Any moderate/severe COPD exacerbation in the 4 weeks preceding the screening visit. * Subjects on long-term oxygen therapy (LTOT), defined as prescribed continuous oxygen use for \>14 hours/day. * Clinically diagnosed history of drug or alcohol abuse within 5 years prior to randomization. * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation. * Participation in a formal pulmonary rehabilitation exercise program outside or inside the home, either currently or completed within the previous 6 months. * For subjects who opt to have magnetic resonance imaging (MRI) at participating study sites, there must be no contraindications to MRI, for example known claustrophobia or a pacemaker. Specific MRI contraindications will be determined by the type of MRI scanner available at each site and study personnel should confirm local eligibility requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90 | SBP and DBP were measured in a seated position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Safety Population comprised of all randomized participants who received at least one dose of study medication. This population was based on the treatment the participant received. |
| Change From Baseline in Heart Rate | Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90 | Heart rate was measured in a seated position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90 | Twelve-lead electrocardiograms (ECG) were obtained using an automated ECG machine to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Baseline (Day 1, Pre-dose) and up to Day 132 | Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), lymphocyte count (Lympho), neutrophil count (Neutro) and platelet count (PC). The laboratory parameters were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Only those participants with increase to grade 3 and increase to grade 4 are presented. |
| Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Baseline (Day 1, Pre-dose) and up to Day 132 | Blood samples were collected for the analysis of following clinical chemistry parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin (Bil),calcium (Ca), cholesterol (Chol), creatinine (Creat), glucose(Gl), phosphate (Phos), potassium (Pot) and sodium (Sod). The laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Values (Hyper and hypo) for Ca, Gl, Pot, Phos and Sod is presented. Only those participants with increase to grade 3 and increase to grade 4 are presented. |
| Change From Baseline in Urinalysis Parameter; Specific Gravity: Placebo-Female Participants | Baseline (Day 1, Pre-dose), Days 28, 56 and 90 | Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Urinalysis Parameter; Specific Gravity: GSK2881078 1.0 mg- Female Participants | Baseline (Day 1, Pre-dose), Days 14 and 90 | Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Urinalysis Parameter; Specific Gravity: Male Participants | Baseline (Day 1, Pre-dose), Days 28 and 90 | Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH): Placebo- Female Participants | Baseline (Day 1, Pre-dose), Days 28, 56 and 90 | Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Urinalysis Parameter; pH: GSK2881078 1.0 mg- Female Participants | Baseline (Day 1, Pre-dose), Days 14 and 90 | Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Urinalysis Parameter; pH: Male Participants | Baseline (Day 1, Pre-dose), Days 28 and 90 | Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Baseline (Day 1, Pre-dose) and up to Day 132 | Urine samples were collected to analyze parameters including glucose, occult blood (OB) and protein levels by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as increase to trace, increase to 1+ (low concentrations present), increase to 2+ (moderate concentrations present) and increase to 3+ (high concentrations present) indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for worst-case post-Baseline relative to Baseline is presented. |
| Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | Up to Day 132 | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had SAEs and non-SAEs are presented. |
| Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | Baseline (Day 1, Pre-dose), Day 28 | Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100\*\[(post-dose value minus Baseline value)/ Baseline value\]. Adjusted means and standard error (SE) are presented. Analysis Population comprised of the participants in the 'All Participants (all randomized participants who received at least one dose of study medication)' Population having Baseline and at least one post-Baseline assessment of the treatment the participant was randomized to. |
| Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | Baseline (Day 1, Pre-dose), Day 56 | Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100\*\[(post-dose value minus Baseline value)/ Baseline value\]. Adjusted means and SE are presented. |
| Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | Baseline (Day 1, Pre-dose), Day 90 | Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100\*\[(post-dose value minus Baseline value)/ Baseline value\]. Adjusted means and SE are presented. |
| Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | Baseline (Day 1, Pre-dose), Day 28 | Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | Baseline (Day 1, Pre-dose), Day 56 | Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | Baseline (Day 1, Pre-dose), Day 90 | Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 56 | Baseline (Day -9), Day 56 | The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The 'amount' domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty' domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for 'amount' and 0 to 20 for 'difficulty'. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented for averaged weekly difficulty score. |
| Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 90 | Baseline (Day -9), Day 90 | The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The 'amount' domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty' domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for 'amount' and 0 to 20 for 'difficulty'. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented for averaged weekly difficulty score. |
| Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 56 | Baseline (Day -9), Day 56 | The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The 'amount' domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty' domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for 'amount' and 0 to 20 for 'difficulty'. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented for averaged weekly amount score. |
| Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 90 | Baseline (Day -9), Day 90 | The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The 'amount' domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty' domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for 'amount' and 0 to 20 for 'difficulty'. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented for averaged weekly amount score. |
| Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 56 | Baseline (Day -9), Day 56 | The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains(amount and difficulty). The'amount'domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty'domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for'amount'and 0 to 20 for'difficulty. The raw scores were then transformed to a 0 to 100 Rasch scale for each domain. The 'total score' was obtained by calculating the average between two domains. Total score has the range from 0 to 100. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented |
| Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 90 | Baseline (Day -9), Day 90 | The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains(amount and difficulty). The'amount'domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty'domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for'amount'and 0 to 20 for'difficulty. The raw scores were then transformed to a 0 to 100 Rasch scale for each domain. The 'total score' was obtained by calculating the average between two domains. Total score has the range from 0 to 100. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Baseline (Day -9), Days 56 and 90 | Steps per day was assessed using an accelerometer, a clinically validated physical activity monitor which was used to measure the levels of physical activity. Participants wore an accelerometer for 7 days during individual timepoint. Values at Baseline, Day 56 and Day 90 were the average values collected from an accelerometer for 7 days after the Day -9, Day 56 and Day 90. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Baseline (Day -9), Days 56 and 90 | Vector magnitude unit per wear time was assessed using an accelerometer, a clinically validated physical activity monitor which was used to measure the levels of physical activity. Participants wore an accelerometer for 7 days during individual timepoint. Values at Baseline, Day 56 and Day 90 were the average values collected from accelerometer for 7 days after the Day -9, Day 56 and Day 90. Data from an accelerator was uploaded to a central site. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Days 14, 28, 56 and 90 | Participant-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to assess the participant's impression of change in their disease severity since the beginning of the study. Responses to the PGIC question were on a 7 point Likert scale: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. Number of participants with PGIC score is presented by treatment group, visit and by 7 response categories. |
| Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Days 1 and 90 | PGRS is a single global question and was asked to participants to rate their COPD severity on a four point scale ranging from 1 to 4 (1=mild, 2=moderate, 3=severe, 4=very severe). Number of participants with PGRS score ranging from mild to very severe are presented over time. |
| Change From Baseline in St. George Respiratory Questionnaire (SGRQ) for COPD (SGRQ-c) Total Score | Baseline (Day 1, Pre-dose), Day 90 | SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Total score was calculated by summing the weight to all the positive responses in each component. Total score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in SGRQ-c Symptoms Score | Baseline (Day 1, Pre-dose), Day 90 | SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Symptoms component consisted of questions 1 to 7 in Part 1. Symptoms score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in SGRQ-c Activity Score | Baseline (Day 1, Pre-dose), Day 90 | SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Activity component consisted of questions 9 and 12 in Part 2 of the questionnaire. Activity score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in SGRQ-c Impact Score | Baseline (Day 1, Pre-dose), Day 90 | SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Impact component consisted of questions 8, 10, 11, 13, 14 in Part 2 of the questionnaire. Impact score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Baseline (Day 1, Pre-dose), Days 56 and 90 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 measurements were collected using a spirometer. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Baseline (Day 1, Pre-dose), Days 56 and 90 | A bung size-specific to the participant was placed in the nostril deemed to be most patent by the investigator. The participant was asked to make a maximum voluntary sniff effort via a peak flow meter and the greatest effort from 10 repeat measurements were recorded. SnIP was measured in centimeter of water (cm H2O). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | Baseline (Day 1, Pre-dose), Day 28 | Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Volume of Distribution at Steady State (Vss) of GSK2881078 Following Oral Dose in Participants | Day 14 (Pre-dose), Day 28 (Pre-dose and at 1 to 4 hours Post-dose), Day 56 (at 5 to 8 hours Post-dose), Day 90 (Pre-dose) | Blood samples were collected at designated timepoints. PK parameters of GSK2881078 were calculated using non-compartmental methods. |
| Clearance (CL) of GSK2881078 Following Oral Dose in Participants | Day 14 (Pre-dose), Day 28 (Pre-dose and at 1 to 4 hours Post-dose), Day 56 (at 5 to 8 hours Post-dose), Day 90 (Pre-dose) | Blood samples were collected at designated timepoints. Pharmacokinetics (PK) parameters of GSK2881078 were calculated using non-compartmental methods. |
| Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | Baseline (Day 1, Pre-dose), Day 56 | Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | Baseline (Day 1, Pre-dose), Day 90 | Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | Baseline (Day 1, Pre-dose), Day 28 | Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | Baseline (Day 1, Pre-dose), Day 56 | Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | Baseline (Day 1, Pre-dose), Day 90 | Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 28 | Baseline (Day 1, Pre-dose), Day 28 | Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores \<=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 56 | Baseline (Day 1, Pre-dose), Day 56 | Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores \<=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 90 | Baseline (Day 1, Pre-dose), Day 90 | Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores \<=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 28 | Baseline (Day 1, Pre-dose), Day 28 | 'Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 56 | Baseline (Day 1, Pre-dose), Day 56 | 'Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 90 | Baseline (Day 1, Pre-dose), Day 90 | 'Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 28 | Baseline (Day 1, Pre-dose), Day 28 | ''Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 56 | Baseline (Day 1, Pre-dose), Day 56 | 'Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 90 | Baseline (Day 1, Pre-dose), Day 90 | 'Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Constant Work Rate (CWR) Duration From Endurance Shuttle Walking Test | Baseline (Day 1, Pre-dose), Day 90 | The endurance shuttle walk test is a CWR test requiring the participant to walk around a flat 10 meter track at a constant individualized pace. The test was externally paced, set to elicit a maximal exercise response (pace was based on a fixed percentage of prior incremental shuttle walk test performance, which determined a participant's peak exercise capacity). CWR duration is the time in seconds required by a participant to cover a flat 10 meter track during this test. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using analysis of covariance (ANCOVA) model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Peak Performance From Incremental Shuttle Walking Test | Baseline (Highest non-missing pre-dose assessment from Day-9 and Day 1), Day 90 | An incremental shuttle walk test is an externally paced maximal exercise test which determined a participant's peak exercise capacity. The maximum duration of the test is 20 minutes. Peak performance was measured in meters, which was defined as the maximum distance covered by a participant until the participant can no longer continue walking during this test. Baseline was defined as the highest non-missing pre-dose assessment from Day -9 and Day 1. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. |
| Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 56 | Baseline (Day 1, Pre-dose), Day 56 | The CAT is a short and simple participant-completed questionnaire which was developed for use in routine clinical practice to measure the health status of participants with COPD. The CAT is an 8-item questionnaire suitable for completion by all participants diagnosed with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (no impairment) to 5 (maximum impairment). A total CAT score was calculated by summing the non-missing scores of the eight items with a scoring range of 0-40. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
| Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 90 | Baseline (Day 1, Pre-dose), Day 90 | The CAT is a short and simple participant-completed questionnaire which was developed for use in routine clinical practice to measure the health status of participants with COPD. The CAT is an 8-item questionnaire suitable for completion by all participants diagnosed with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (no impairment) to 5 (maximum impairment). A total CAT score was calculated by summing the non-missing scores of the eight items with a scoring range of 0-40. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. |
Countries
Germany, United Kingdom, United States
Participant flow
Recruitment details
This was a Phase II, double-blind, randomized, multicenter study to evaluate the safety and efficacy of GSK2881078 over 13 weeks of once daily oral dosing, first time administered in older men and post-menopausal female participants with chronic obstructive pulmonary disease (COPD) and muscle weakness, participating in home exercise.
Pre-assignment details
A total of 200 participants were screened and 97 participants were enrolled in this study. Of which, 96 participants were randomized and received the study treatment. The remaining 1 participant was randomized without fulfilling the inclusion and exclusion criteria and therefore did not receive study medication.
Participants by arm
| Arm | Count |
|---|---|
| Placebo- Female Participants Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks. | 23 |
| GSK2881078 1.0 mg- Female Participants Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 0.5 milligram (mg) once daily over 13 weeks. | 24 |
| Placebo- Male Participants Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks. | 24 |
| GSK2881078 2.0 mg- Male Participants Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 1.0 mg once daily over 13 weeks. | 25 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 5 | 3 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 0 | 1 |
| Overall Study | Protocol-defined stopping criteria | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo- Female Participants | GSK2881078 1.0 mg- Female Participants | Placebo- Male Participants | GSK2881078 2.0 mg- Male Participants | Total |
|---|---|---|---|---|---|
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 7.16 | 64.2 Years STANDARD_DEVIATION 7.93 | 64.0 Years STANDARD_DEVIATION 7.27 | 67.2 Years STANDARD_DEVIATION 6.08 | 65.1 Years STANDARD_DEVIATION 7.14 |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized White-White/Caucasian/European Heritage | 23 Participants | 23 Participants | 22 Participants | 23 Participants | 91 Participants |
| Sex: Female, Male Female | 23 Participants | 24 Participants | 0 Participants | 0 Participants | 47 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 24 Participants | 25 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 24 | 0 / 24 | 0 / 25 |
| other Total, other adverse events | 15 / 23 | 18 / 24 | 13 / 24 | 17 / 25 |
| serious Total, serious adverse events | 1 / 23 | 2 / 24 | 2 / 24 | 0 / 25 |
Outcome results
Primary
Change From Baseline in Heart Rate
Heart rate was measured in a seated position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Heart Rate | Day 14,n=22,23,23,24 | -0.7 Beats per minute | Standard Deviation 9.79 |
| Placebo- Female Participants | Change From Baseline in Heart Rate | Day 28,n=22,20,23,24 | 2.2 Beats per minute | Standard Deviation 8.11 |
| Placebo- Female Participants | Change From Baseline in Heart Rate | Day 56,n=21,19,20,21 | 0.2 Beats per minute | Standard Deviation 8.87 |
| Placebo- Female Participants | Change From Baseline in Heart Rate | Day 90,n=21,18,18,20 | 1.1 Beats per minute | Standard Deviation 7.99 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Heart Rate | Day 28,n=22,20,23,24 | 2.1 Beats per minute | Standard Deviation 9.64 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Heart Rate | Day 56,n=21,19,20,21 | -1.0 Beats per minute | Standard Deviation 8.81 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Heart Rate | Day 90,n=21,18,18,20 | 2.3 Beats per minute | Standard Deviation 10.34 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Heart Rate | Day 14,n=22,23,23,24 | 3.3 Beats per minute | Standard Deviation 9.16 |
| Placebo- Male Participants | Change From Baseline in Heart Rate | Day 56,n=21,19,20,21 | 2.8 Beats per minute | Standard Deviation 7.17 |
| Placebo- Male Participants | Change From Baseline in Heart Rate | Day 28,n=22,20,23,24 | 4.6 Beats per minute | Standard Deviation 10.71 |
| Placebo- Male Participants | Change From Baseline in Heart Rate | Day 90,n=21,18,18,20 | 7.4 Beats per minute | Standard Deviation 10.23 |
| Placebo- Male Participants | Change From Baseline in Heart Rate | Day 14,n=22,23,23,24 | 1.7 Beats per minute | Standard Deviation 10.61 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Heart Rate | Day 90,n=21,18,18,20 | -0.6 Beats per minute | Standard Deviation 8.17 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Heart Rate | Day 28,n=22,20,23,24 | -1.7 Beats per minute | Standard Deviation 10.71 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Heart Rate | Day 14,n=22,23,23,24 | -0.4 Beats per minute | Standard Deviation 6.6 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Heart Rate | Day 56,n=21,19,20,21 | 0.2 Beats per minute | Standard Deviation 6.36 |
Primary
Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28
Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 28
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | 4.2 Kilograms | Standard Error 3.01 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | 10.0 Kilograms | Standard Error 3.08 |
| Placebo- Male Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | 3.0 Kilograms | Standard Error 5.06 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | 16.5 Kilograms | Standard Error 4.9 |
90% CI: [-1.4, 13.2]
90% CI: [1.6, 25.5]
Primary
Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56
Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | 0.6 Kilograms | Standard Error 4.29 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | 21.3 Kilograms | Standard Error 4.5 |
| Placebo- Male Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | 8.3 Kilograms | Standard Error 7.69 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | 15.7 Kilograms | Standard Error 7.69 |
90% CI: [10.1, 31.2]
90% CI: [-11.1, 25.8]
Primary
Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90
Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | 12.3 Kilograms | Standard Error 4.31 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | 20.3 Kilograms | Standard Error 4.45 |
| Placebo- Male Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | 14.2 Kilograms | Standard Error 5.17 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | 26.0 Kilograms | Standard Error 4.91 |
90% CI: [-2.5, 18.4]
90% CI: [-0.5, 24]
Primary
Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB)
Twelve-lead electrocardiograms (ECG) were obtained using an automated ECG machine to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 90,n=20,17,18,17 | 3.600 Milliseconds | Standard Deviation 10.3526 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 90,n=21,18,18,20 | 4.063 Milliseconds | Standard Deviation 16.916 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 90,n=21,18,17,20 | -0.270 Milliseconds | Standard Deviation 9.3111 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 56,n=20,18,18,18 | 1.333 Milliseconds | Standard Deviation 8.5039 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 14,n=21,21,21,21 | 1.749 Milliseconds | Standard Deviation 11.7762 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,Day 14,n=22,23,22,24 | -1.303 Milliseconds | Standard Deviation 9.9261 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 28,n=21,19,21,21 | 0.362 Milliseconds | Standard Deviation 15.7742 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 28,n=22,20,22,24 | -0.061 Milliseconds | Standard Deviation 7.934 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 56,n=3,3,4,6 | -13.556 Milliseconds | Standard Deviation 11.3741 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 14,n=22,23,23,24 | 4.364 Milliseconds | Standard Deviation 22.8107 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 28,n=22,20,23,24 | 1.000 Milliseconds | Standard Deviation 7.7014 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 28,n=4,3,4,7 | -1.167 Milliseconds | Standard Deviation 12.1549 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 56,n=21,19,20,21 | -0.095 Milliseconds | Standard Deviation 5.9639 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 90,n=3,3,2,6 | 1.333 Milliseconds | Standard Deviation 15.9199 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 90,n=21,18,18,20 | -2.397 Milliseconds | Standard Deviation 14.1494 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 56,n=21,19,20,21 | 1.302 Milliseconds | Standard Deviation 12.122 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 14,n=4,5,4,7 | -4.333 Milliseconds | Standard Deviation 26.21 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 14,n=22,23,23,24 | 0.576 Milliseconds | Standard Deviation 19.8239 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 28,n=22,20,23,24 | -1.333 Milliseconds | Standard Deviation 23.53 |
| Placebo- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 56,n=21,19,20,21 | -0.127 Milliseconds | Standard Deviation 13.5567 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 90,n=20,17,18,17 | -12.627 Milliseconds | Standard Deviation 11.5776 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 56,n=21,19,20,21 | -13.947 Milliseconds | Standard Deviation 18.3657 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 56,n=3,3,4,6 | -7.667 Milliseconds | Standard Deviation 9.7125 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 56,n=20,18,18,18 | -12.222 Milliseconds | Standard Deviation 10.2975 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 28,n=22,20,23,24 | 6.200 Milliseconds | Standard Deviation 28.2707 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 90,n=21,18,18,20 | -16.352 Milliseconds | Standard Deviation 20.7511 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,Day 14,n=22,23,22,24 | -0.377 Milliseconds | Standard Deviation 7.2588 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 90,n=3,3,2,6 | -13.111 Milliseconds | Standard Deviation 3.0972 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 28,n=22,20,23,24 | -16.133 Milliseconds | Standard Deviation 26.2775 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 14,n=21,21,21,21 | -7.143 Milliseconds | Standard Deviation 9.271 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 56,n=21,19,20,21 | 1.842 Milliseconds | Standard Deviation 5.4096 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 28,n=21,19,21,21 | -12.930 Milliseconds | Standard Deviation 11.7707 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 14,n=22,23,23,24 | -14.290 Milliseconds | Standard Deviation 17.7216 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 90,n=21,18,17,20 | -6.167 Milliseconds | Standard Deviation 28.9117 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 14,n=4,5,4,7 | 2.193 Milliseconds | Standard Deviation 12.5624 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 56,n=21,19,20,21 | 0.596 Milliseconds | Standard Deviation 6.525 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 90,n=21,18,18,20 | -2.444 Milliseconds | Standard Deviation 4.536 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 14,n=22,23,23,24 | 1.362 Milliseconds | Standard Deviation 10.4736 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 28,n=22,20,22,24 | -4.717 Milliseconds | Standard Deviation 19.3177 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 28,n=4,3,4,7 | 13.667 Milliseconds | Standard Deviation 24.7678 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 14,n=21,21,21,21 | -1.235 Milliseconds | Standard Deviation 11.3507 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,Day 14,n=22,23,22,24 | -2.455 Milliseconds | Standard Deviation 12.6556 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 28,n=22,20,22,24 | -2.333 Milliseconds | Standard Deviation 17.5966 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 56,n=21,19,20,21 | 0.483 Milliseconds | Standard Deviation 7.5436 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 90,n=21,18,17,20 | -3.373 Milliseconds | Standard Deviation 9.6845 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 14,n=22,23,23,24 | -0.464 Milliseconds | Standard Deviation 7.4791 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 28,n=22,20,23,24 | -1.478 Milliseconds | Standard Deviation 5.5047 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 56,n=21,19,20,21 | -1.100 Milliseconds | Standard Deviation 4.9631 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 90,n=21,18,18,20 | 1.333 Milliseconds | Standard Deviation 25.4163 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 14,n=22,23,23,24 | -0.638 Milliseconds | Standard Deviation 22.5431 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 28,n=22,20,23,24 | -4.203 Milliseconds | Standard Deviation 23.3733 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 56,n=21,19,20,21 | -1.533 Milliseconds | Standard Deviation 20.5897 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 90,n=21,18,18,20 | -4.574 Milliseconds | Standard Deviation 17.1825 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 28,n=21,19,21,21 | -0.489 Milliseconds | Standard Deviation 10.5492 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 56,n=20,18,18,18 | 1.093 Milliseconds | Standard Deviation 10.0462 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 90,n=20,17,18,17 | 2.657 Milliseconds | Standard Deviation 12.2002 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 14,n=4,5,4,7 | 12.917 Milliseconds | Standard Deviation 13.6582 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 28,n=4,3,4,7 | -7.667 Milliseconds | Standard Deviation 8.8192 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 56,n=3,3,4,6 | 13.417 Milliseconds | Standard Deviation 8.0017 |
| Placebo- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 90,n=3,3,2,6 | 32.000 Milliseconds | Standard Deviation 1.4142 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 28,n=22,20,23,24 | -1.750 Milliseconds | Standard Deviation 22.6539 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 14,n=22,23,23,24 | -0.597 Milliseconds | Standard Deviation 15.5697 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 56,n=3,3,4,6 | -9.500 Milliseconds | Standard Deviation 7.2411 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 90,n=20,17,18,17 | -11.804 Milliseconds | Standard Deviation 11.7207 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 90,n=21,18,18,20 | 1.333 Milliseconds | Standard Deviation 6.3005 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 56,n=21,19,20,21 | -0.413 Milliseconds | Standard Deviation 4.6271 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 28,n=22,20,22,24 | 4.139 Milliseconds | Standard Deviation 15.5796 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 14,n=4,5,4,7 | 0.571 Milliseconds | Standard Deviation 11.018 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 28,n=22,20,23,24 | -0.542 Milliseconds | Standard Deviation 3.3547 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QRS Duration,Day 14,n=22,23,23,24 | 1.167 Milliseconds | Standard Deviation 4.1772 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,Day 14,n=22,23,22,24 | -2.875 Milliseconds | Standard Deviation 24.337 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 28,n=4,3,4,7 | -10.238 Milliseconds | Standard Deviation 11.6678 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 90,n=21,18,17,20 | 3.033 Milliseconds | Standard Deviation 20.7947 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 14,n=21,21,21,21 | -2.698 Milliseconds | Standard Deviation 9.7085 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | PR interval,,Day 56,n=21,19,20,21 | 10.444 Milliseconds | Standard Deviation 27.5133 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 28,n=21,19,21,21 | -4.340 Milliseconds | Standard Deviation 12.8445 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 90,n=21,18,18,20 | -5.167 Milliseconds | Standard Deviation 17.7759 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QT Interval,Day 56,n=21,19,20,21 | -1.857 Milliseconds | Standard Deviation 14.6881 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcB Interval,Day 90,n=3,3,2,6 | -10.278 Milliseconds | Standard Deviation 9.6088 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in PR Interval, QRS Duration, QT Interval, QT Interval Corrected for Heart Rate by Fridericia's Formula (QTcF) and QT Interval Corrected for Heart Rate by Bazett's Formula (QTcB) | QTcF Interval,Day 56,n=20,18,18,18 | -3.357 Milliseconds | Standard Deviation 10.5127 |
Primary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP and DBP were measured in a seated position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Safety Population comprised of all randomized participants who received at least one dose of study medication. This population was based on the treatment the participant received.
Time frame: Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 14,n=22,23,23,24 | 3.0 Millimeters of mercury | Standard Deviation 19.63 |
| Placebo- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 28,n=22,20,23,24 | 3.7 Millimeters of mercury | Standard Deviation 12.76 |
| Placebo- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 56,n=21,19,20,21 | 3.3 Millimeters of mercury | Standard Deviation 14.96 |
| Placebo- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 90,n=21,18,18,20 | 1.0 Millimeters of mercury | Standard Deviation 14.23 |
| Placebo- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 14,n=22,23,23,24 | 1.9 Millimeters of mercury | Standard Deviation 6.88 |
| Placebo- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 28,n=22,20,23,24 | 3.6 Millimeters of mercury | Standard Deviation 7.08 |
| Placebo- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 56,n=21,19,20,21 | 2.1 Millimeters of mercury | Standard Deviation 7 |
| Placebo- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 90,n=21,18,18,20 | -1.0 Millimeters of mercury | Standard Deviation 6.47 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 28,n=22,20,23,24 | 1.4 Millimeters of mercury | Standard Deviation 7.58 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 14,n=22,23,23,24 | 1.1 Millimeters of mercury | Standard Deviation 6.93 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 28,n=22,20,23,24 | -0.1 Millimeters of mercury | Standard Deviation 12.82 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 90,n=21,18,18,20 | 2.9 Millimeters of mercury | Standard Deviation 8.37 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 56,n=21,19,20,21 | 2.9 Millimeters of mercury | Standard Deviation 6.07 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 90,n=21,18,18,20 | 7.6 Millimeters of mercury | Standard Deviation 15.56 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 56,n=21,19,20,21 | 7.8 Millimeters of mercury | Standard Deviation 16.38 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 14,n=22,23,23,24 | 2.1 Millimeters of mercury | Standard Deviation 11.03 |
| Placebo- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 56,n=21,19,20,21 | -2.5 Millimeters of mercury | Standard Deviation 10.38 |
| Placebo- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 56,n=21,19,20,21 | -2.4 Millimeters of mercury | Standard Deviation 17.68 |
| Placebo- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 90,n=21,18,18,20 | -4.2 Millimeters of mercury | Standard Deviation 18.52 |
| Placebo- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 14,n=22,23,23,24 | -3.4 Millimeters of mercury | Standard Deviation 6.2 |
| Placebo- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 28,n=22,20,23,24 | 0.7 Millimeters of mercury | Standard Deviation 7.9 |
| Placebo- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 90,n=21,18,18,20 | -0.1 Millimeters of mercury | Standard Deviation 12.98 |
| Placebo- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 14,n=22,23,23,24 | -2.1 Millimeters of mercury | Standard Deviation 9.33 |
| Placebo- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 28,n=22,20,23,24 | 2.6 Millimeters of mercury | Standard Deviation 14.39 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 56,n=21,19,20,21 | 1.3 Millimeters of mercury | Standard Deviation 9.12 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 90,n=21,18,18,20 | 5.8 Millimeters of mercury | Standard Deviation 18.61 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 28,n=22,20,23,24 | 5.8 Millimeters of mercury | Standard Deviation 9.49 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP,Day 14,n=22,23,23,24 | 3.1 Millimeters of mercury | Standard Deviation 11.65 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 14,n=22,23,23,24 | -0.4 Millimeters of mercury | Standard Deviation 7.47 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 90,n=21,18,18,20 | 0.6 Millimeters of mercury | Standard Deviation 6.95 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 56,n=21,19,20,21 | -1.6 Millimeters of mercury | Standard Deviation 8.16 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP,Day 28,n=22,20,23,24 | 1.0 Millimeters of mercury | Standard Deviation 5.36 |
Primary
Change From Baseline in Urinalysis Parameter; pH: GSK2881078 1.0 mg- Female Participants
Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 14 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; pH: GSK2881078 1.0 mg- Female Participants | Day 14,n=1 | 1.0000 pH | — |
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; pH: GSK2881078 1.0 mg- Female Participants | Day 90,n=18 | -0.1111 pH | Standard Deviation 0.60768 |
Primary
Change From Baseline in Urinalysis Parameter; pH: Male Participants
Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 28 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; pH: Male Participants | Day 28,n=1,1 | 1.0000 pH | — |
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; pH: Male Participants | Day 90,n=19,20 | -0.1579 pH | Standard Deviation 0.72749 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Urinalysis Parameter; pH: Male Participants | Day 28,n=1,1 | 0.5000 pH | — |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Urinalysis Parameter; pH: Male Participants | Day 90,n=19,20 | 0.3000 pH | Standard Deviation 0.71451 |
Primary
Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH): Placebo- Female Participants
Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 28, 56 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH): Placebo- Female Participants | Day 28,n=1 | 0.0000 pH | — |
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH): Placebo- Female Participants | Day 56,n=1 | -0.5000 pH | — |
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH): Placebo- Female Participants | Day 90,n=21 | 0.0000 pH | Standard Deviation 0.80623 |
Primary
Change From Baseline in Urinalysis Parameter; Specific Gravity: GSK2881078 1.0 mg- Female Participants
Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 14 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: GSK2881078 1.0 mg- Female Participants | Day 90,n=18 | 0.0049 Ratio | Standard Deviation 0.00711 |
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: GSK2881078 1.0 mg- Female Participants | Day 14,n=1 | 0.000 Ratio | — |
Primary
Change From Baseline in Urinalysis Parameter; Specific Gravity: Male Participants
Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 28 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: Male Participants | Day 28,n=1,1 | -0.0080 Ratio | — |
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: Male Participants | Day 90,n=19,20 | 0.0017 Ratio | Standard Deviation 0.0087 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: Male Participants | Day 28,n=1,1 | 0.0040 Ratio | — |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: Male Participants | Day 90,n=19,20 | 0.0018 Ratio | Standard Deviation 0.0061 |
Primary
Change From Baseline in Urinalysis Parameter; Specific Gravity: Placebo-Female Participants
Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 28, 56 and 90
Population: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: Placebo-Female Participants | Day 28,n=1 | 0.0030 Ratio | — |
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: Placebo-Female Participants | Day 56,n=1 | 0.0020 Ratio | — |
| Placebo- Female Participants | Change From Baseline in Urinalysis Parameter; Specific Gravity: Placebo-Female Participants | Day 90,n=21 | -0.0006 Ratio | Standard Deviation 0.00612 |
Primary
Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters
Blood samples were collected for the analysis of following clinical chemistry parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin (Bil),calcium (Ca), cholesterol (Chol), creatinine (Creat), glucose(Gl), phosphate (Phos), potassium (Pot) and sodium (Sod). The laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Values (Hyper and hypo) for Ca, Gl, Pot, Phos and Sod is presented. Only those participants with increase to grade 3 and increase to grade 4 are presented.
Time frame: Baseline (Day 1, Pre-dose) and up to Day 132
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hypo,increase to Grade 3 | 2 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | AST, AST increased, increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALT, ALT increased, increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | AST, AST increased, increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Bil, Blood Bil increased, increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Bil, Blood Bil increased, increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALP, ALP increased, increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALT, ALT increased, increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Chol, Chol high,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALP, ALP increased, increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Chol, Chol high,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Creat, Creat increased,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Creat, Creat increased,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Creat, Creat increased,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Chol, Chol high,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Creat, Creat increased,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | AST, AST increased, increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALP, ALP increased, increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Chol, Chol high,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | AST, AST increased, increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALT, ALT increased, increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALP, ALP increased, increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Bil, Blood Bil increased, increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALT, ALT increased, increase to Grade 3 | 1 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Bil, Blood Bil increased, increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Creat, Creat increased,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALT, ALT increased, increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALT, ALT increased, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALP, ALP increased, increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALP, ALP increased, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | AST, AST increased, increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | AST, AST increased, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Bil, Blood Bil increased, increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Bil, Blood Bil increased, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Chol, Chol high,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Chol, Chol high,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Creat, Creat increased,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hypo,increase to Grade 3 | 1 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hypo,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hyper,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hyper,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hypo,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Creat, Creat increased,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Creat, Creat increased,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALP, ALP increased, increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Chol, Chol high,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Chol, Chol high,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALP, ALP increased, increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Bil, Blood Bil increased, increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Pot, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Ca, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Bil, Blood Bil increased, increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALT, ALT increased, increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | AST, AST increased, increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hyper,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | AST, AST increased, increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hypo,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | ALT, ALT increased, increase to Grade 3 | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hypo,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Gl, Hyper,increase to Grade 3 | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Sod, Hyper,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters | Phos, Hypo,increase to Grade 4 | 0 Participants |
Primary
Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), lymphocyte count (Lympho), neutrophil count (Neutro) and platelet count (PC). The laboratory parameters were graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Only those participants with increase to grade 3 and increase to grade 4 are presented.
Time frame: Baseline (Day 1, Pre-dose) and up to Day 132
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count decreased, increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC increased,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count decreased, increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count increased, increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 4 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count increased, increase to Grade 3 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC increased,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count increased, increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count increased, increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC increased,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC increased,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count decreased, increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count decreased, increase to Grade 4 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 3 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count decreased, increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count decreased, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count increased, increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count increased, increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 3 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC increased,increase to Grade 4 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC increased,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count increased, increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count decreased, increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC increased,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count decreased, increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC decreased,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Hb increased, increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Hb, Anemia, increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 3 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Lympho, Lymph count increased, increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | PC, PC increased,increase to Grade 4 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters | Neutro,Neutro count decreased,increase to Grade 4 | 0 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had SAEs and non-SAEs are presented.
Time frame: Up to Day 132
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo- Female Participants | Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | Non-SAEs | 15 Participants |
| Placebo- Female Participants | Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | SAEs | 1 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | SAEs | 2 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | Non-SAEs | 18 Participants |
| Placebo- Male Participants | Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | Non-SAEs | 13 Participants |
| Placebo- Male Participants | Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | SAEs | 2 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | Non-SAEs | 17 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events | SAEs | 0 Participants |
Primary
Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline
Urine samples were collected to analyze parameters including glucose, occult blood (OB) and protein levels by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as increase to trace, increase to 1+ (low concentrations present), increase to 2+ (moderate concentrations present) and increase to 3+ (high concentrations present) indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for worst-case post-Baseline relative to Baseline is presented.
Time frame: Baseline (Day 1, Pre-dose) and up to Day 132
Population: Safety Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 1+ | 0 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 3+ | 0 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 3+ | 0 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to trace | 0 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to trace | 2 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 2+ | 0 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 3+ | 0 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 1+ | 0 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 2+ | 0 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to trace | 1 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 1+ | 1 Participants |
| Placebo- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 2+ | 1 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 1+ | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 2+ | 2 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 3+ | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to trace | 2 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 1+ | 3 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 3+ | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to trace | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 1+ | 1 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to trace | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 2+ | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 3+ | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 2+ | 1 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 3+ | 0 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to trace | 1 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 1+ | 0 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 2+ | 0 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 3+ | 0 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to trace | 1 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 1+ | 1 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 2+ | 0 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to trace | 3 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 1+ | 1 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 2+ | 0 Participants |
| Placebo- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 3+ | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 1+ | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to trace | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to trace | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 1+ | 3 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 3+ | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 2+ | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 3+ | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to 2+ | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 3+ | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | OB: increase to 2+ | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Glucose: increase to 1+ | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline | Protein: increase to trace | 6 Participants |
Primary
Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28
Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100\*\[(post-dose value minus Baseline value)/ Baseline value\]. Adjusted means and standard error (SE) are presented. Analysis Population comprised of the participants in the 'All Participants (all randomized participants who received at least one dose of study medication)' Population having Baseline and at least one post-Baseline assessment of the treatment the participant was randomized to.
Time frame: Baseline (Day 1, Pre-dose), Day 28
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | 4.82 Percentage change | Standard Error 2.406 |
| GSK2881078 1.0 mg- Female Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | 9.34 Percentage change | Standard Error 2.459 |
| Placebo- Male Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | 1.55 Percentage change | Standard Error 2.94 |
| GSK2881078 2.0 mg- Male Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 | 9.35 Percentage change | Standard Error 2.848 |
90% CI: [-1.3, 10.36]
90% CI: [0.83, 14.76]
Primary
Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56
Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100\*\[(post-dose value minus Baseline value)/ Baseline value\]. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | 0.08 Percentage change | Standard Error 2.787 |
| GSK2881078 1.0 mg- Female Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | 16.78 Percentage change | Standard Error 2.925 |
| Placebo- Male Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | 5.73 Percentage change | Standard Error 3.921 |
| GSK2881078 2.0 mg- Male Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 | 11.07 Percentage change | Standard Error 3.922 |
90% CI: [9.86, 23.56]
90% CI: [-4.09, 14.78]
Primary
Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90
Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100\*\[(post-dose value minus Baseline value)/ Baseline value\]. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | 12.76 Percentage change | Standard Error 4.061 |
| GSK2881078 1.0 mg- Female Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | 17.93 Percentage change | Standard Error 4.179 |
| Placebo- Male Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | 7.15 Percentage change | Standard Error 2.759 |
| GSK2881078 2.0 mg- Male Participants | Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 | 14.17 Percentage change | Standard Error 2.632 |
90% CI: [-4.67, 15.01]
90% CI: [0.46, 13.58]
Secondary
Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28
Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 28
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | -0.240 Kilograms | Standard Error 0.0974 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | 0.642 Kilograms | Standard Error 0.1023 |
| Placebo- Male Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | 0.055 Kilograms | Standard Error 0.192 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | 0.346 Kilograms | Standard Error 0.1831 |
90% CI: [0.643, 1.121]
90% CI: [-0.156, 0.738]
Secondary
Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56
Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | -0.134 Kilograms | Standard Error 0.141 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | 0.848 Kilograms | Standard Error 0.154 |
| Placebo- Male Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | -0.464 Kilograms | Standard Error 0.1887 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | 0.663 Kilograms | Standard Error 0.1829 |
90% CI: [0.629, 1.334]
90% CI: [0.682, 1.571]
Secondary
Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90
Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | -0.434 Kilograms | Standard Error 0.1657 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | 0.946 Kilograms | Standard Error 0.1818 |
| Placebo- Male Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | -0.225 Kilograms | Standard Error 0.2306 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | 0.899 Kilograms | Standard Error 0.2117 |
90% CI: [0.964, 1.795]
90% CI: [0.594, 1.654]
Secondary
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 56
The CAT is a short and simple participant-completed questionnaire which was developed for use in routine clinical practice to measure the health status of participants with COPD. The CAT is an 8-item questionnaire suitable for completion by all participants diagnosed with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (no impairment) to 5 (maximum impairment). A total CAT score was calculated by summing the non-missing scores of the eight items with a scoring range of 0-40. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 56 | -0.8 Scores on a Scale | Standard Error 0.92 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 56 | -1.2 Scores on a Scale | Standard Error 0.97 |
| Placebo- Male Participants | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 56 | -0.4 Scores on a Scale | Standard Error 1.14 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 56 | -1.0 Scores on a Scale | Standard Error 1.14 |
90% CI: [-2.6, 1.9]
90% CI: [-3.4, 2.1]
Secondary
Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 90
The CAT is a short and simple participant-completed questionnaire which was developed for use in routine clinical practice to measure the health status of participants with COPD. The CAT is an 8-item questionnaire suitable for completion by all participants diagnosed with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (no impairment) to 5 (maximum impairment). A total CAT score was calculated by summing the non-missing scores of the eight items with a scoring range of 0-40. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 90 | -1.3 Scores on a Scale | Standard Error 0.79 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 90 | -2.2 Scores on a Scale | Standard Error 0.85 |
| Placebo- Male Participants | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 90 | -1.4 Scores on a Scale | Standard Error 0.94 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 90 | 0.8 Scores on a Scale | Standard Error 0.9 |
90% CI: [-2.9, 1.1]
90% CI: [0, 4.5]
Secondary
Change From Baseline in Constant Work Rate (CWR) Duration From Endurance Shuttle Walking Test
The endurance shuttle walk test is a CWR test requiring the participant to walk around a flat 10 meter track at a constant individualized pace. The test was externally paced, set to elicit a maximal exercise response (pace was based on a fixed percentage of prior incremental shuttle walk test performance, which determined a participant's peak exercise capacity). CWR duration is the time in seconds required by a participant to cover a flat 10 meter track during this test. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using analysis of covariance (ANCOVA) model. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Constant Work Rate (CWR) Duration From Endurance Shuttle Walking Test | -6.5 Seconds | Standard Error 26.78 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Constant Work Rate (CWR) Duration From Endurance Shuttle Walking Test | 4.6 Seconds | Standard Error 29.25 |
| Placebo- Male Participants | Change From Baseline in Constant Work Rate (CWR) Duration From Endurance Shuttle Walking Test | 105.1 Seconds | Standard Error 54.94 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Constant Work Rate (CWR) Duration From Endurance Shuttle Walking Test | -44.2 Seconds | Standard Error 51.97 |
90% CI: [-57.1, 79.2]
90% CI: [-280.6, -18.1]
Secondary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 measurements were collected using a spirometer. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 56 and 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 56,n=21,19,21,21 | -0.000 Liters | Standard Deviation 0.0918 |
| Placebo- Female Participants | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 90,n=20,18,18,20 | 0.002 Liters | Standard Deviation 0.097 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 90,n=20,18,18,20 | -0.024 Liters | Standard Deviation 0.0833 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 56,n=21,19,21,21 | -0.028 Liters | Standard Deviation 0.0747 |
| Placebo- Male Participants | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 56,n=21,19,21,21 | 0.012 Liters | Standard Deviation 0.1342 |
| Placebo- Male Participants | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 90,n=20,18,18,20 | 0.050 Liters | Standard Deviation 0.113 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 56,n=21,19,21,21 | -0.016 Liters | Standard Deviation 0.2377 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) | Day 90,n=20,18,18,20 | 0.007 Liters | Standard Deviation 0.2208 |
Secondary
Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 56
The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The 'amount' domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty' domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for 'amount' and 0 to 20 for 'difficulty'. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented for averaged weekly amount score.
Time frame: Baseline (Day -9), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 56 | 3.3 Scores on a Scale | Standard Error 1.09 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 56 | 0.2 Scores on a Scale | Standard Error 1.24 |
| Placebo- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 56 | 2.5 Scores on a Scale | Standard Error 1.83 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 56 | 2.3 Scores on a Scale | Standard Error 1.77 |
90% CI: [-5.9, -0.3]
90% CI: [-4.6, 4.2]
Secondary
Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 90
The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The 'amount' domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty' domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for 'amount' and 0 to 20 for 'difficulty'. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented for averaged weekly amount score.
Time frame: Baseline (Day -9), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 90 | -0.2 Scores on a Scale | Standard Error 2.05 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 90 | 3.8 Scores on a Scale | Standard Error 1.98 |
| Placebo- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 90 | -0.8 Scores on a Scale | Standard Error 2.33 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 90 | 2.7 Scores on a Scale | Standard Error 2.47 |
90% CI: [-0.8, 8.8]
90% CI: [-2.3, 9.4]
Secondary
Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 56
The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The 'amount' domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty' domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for 'amount' and 0 to 20 for 'difficulty'. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented for averaged weekly difficulty score.
Time frame: Baseline (Day -9), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 56 | 3.7 Scores on a Scale | Standard Error 1.59 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 56 | -1.1 Scores on a Scale | Standard Error 1.8 |
| Placebo- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 56 | 1.3 Scores on a Scale | Standard Error 2.16 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 56 | -0.8 Scores on a Scale | Standard Error 2.08 |
90% CI: [-8.9, -0.6]
90% CI: [-7.2, 3.1]
Secondary
Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 90
The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The 'amount' domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty' domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for 'amount' and 0 to 20 for 'difficulty'. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented for averaged weekly difficulty score.
Time frame: Baseline (Day -9), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 90 | 2.0 Scores on a Scale | Standard Error 1.9 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 90 | -2.9 Scores on a Scale | Standard Error 1.84 |
| Placebo- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 90 | 2.8 Scores on a Scale | Standard Error 2.56 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 90 | -1.2 Scores on a Scale | Standard Error 2.65 |
90% CI: [-9.5, -0.4]
90% CI: [-10.3, 2.2]
Secondary
Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 56
The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains(amount and difficulty). The'amount'domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty'domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for'amount'and 0 to 20 for'difficulty. The raw scores were then transformed to a 0 to 100 Rasch scale for each domain. The 'total score' was obtained by calculating the average between two domains. Total score has the range from 0 to 100. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented
Time frame: Baseline (Day -9), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 56 | 3.7 Scores on a Scale | Standard Error 0.89 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 56 | -0.5 Scores on a Scale | Standard Error 1.03 |
| Placebo- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 56 | 2.1 Scores on a Scale | Standard Error 1.09 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 56 | 0.5 Scores on a Scale | Standard Error 1.05 |
90% CI: [-6.5, -1.9]
90% CI: [-4.1, 1.1]
Secondary
Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 90
The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains(amount and difficulty). The'amount'domain was covered by 2 questions combined with 2 activity monitor outputs. The 'difficulty'domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for'amount'and 0 to 20 for'difficulty. The raw scores were then transformed to a 0 to 100 Rasch scale for each domain. The 'total score' was obtained by calculating the average between two domains. Total score has the range from 0 to 100. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day -9), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 90 | 1.3 Scores on a Scale | Standard Error 1.2 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 90 | 0.3 Scores on a Scale | Standard Error 1.14 |
| Placebo- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 90 | 1.2 Scores on a Scale | Standard Error 1.57 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 90 | 0.5 Scores on a Scale | Standard Error 1.66 |
90% CI: [-3.8, 1.8]
90% CI: [-4.6, 3.2]
Secondary
Change From Baseline in Peak Performance From Incremental Shuttle Walking Test
An incremental shuttle walk test is an externally paced maximal exercise test which determined a participant's peak exercise capacity. The maximum duration of the test is 20 minutes. Peak performance was measured in meters, which was defined as the maximum distance covered by a participant until the participant can no longer continue walking during this test. Baseline was defined as the highest non-missing pre-dose assessment from Day -9 and Day 1. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Highest non-missing pre-dose assessment from Day-9 and Day 1), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Peak Performance From Incremental Shuttle Walking Test | -10.5 Meters | Standard Error 14.76 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Peak Performance From Incremental Shuttle Walking Test | -17.2 Meters | Standard Error 15.16 |
| Placebo- Male Participants | Change From Baseline in Peak Performance From Incremental Shuttle Walking Test | -7.5 Meters | Standard Error 15.84 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Peak Performance From Incremental Shuttle Walking Test | -42.3 Meters | Standard Error 15.02 |
90% CI: [-42.7, 29.2]
90% CI: [-72, 2.4]
Secondary
Change From Baseline in SGRQ-c Activity Score
SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Activity component consisted of questions 9 and 12 in Part 2 of the questionnaire. Activity score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in SGRQ-c Activity Score | -5.4 Scores on a scale | Standard Error 2 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in SGRQ-c Activity Score | -3.4 Scores on a scale | Standard Error 2.23 |
| Placebo- Male Participants | Change From Baseline in SGRQ-c Activity Score | 1.2 Scores on a scale | Standard Error 2.57 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in SGRQ-c Activity Score | 1.6 Scores on a scale | Standard Error 2.44 |
90% CI: [-3.2, 7.1]
90% CI: [-5.6, 6.5]
Secondary
Change From Baseline in SGRQ-c Impact Score
SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Impact component consisted of questions 8, 10, 11, 13, 14 in Part 2 of the questionnaire. Impact score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in SGRQ-c Impact Score | -2.8 Scores on a scale | Standard Error 2.03 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in SGRQ-c Impact Score | 0.6 Scores on a scale | Standard Error 2.25 |
| Placebo- Male Participants | Change From Baseline in SGRQ-c Impact Score | -2.7 Scores on a scale | Standard Error 1.76 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in SGRQ-c Impact Score | 0.8 Scores on a scale | Standard Error 1.67 |
90% CI: [-1.7, 8.6]
90% CI: [-0.7, 7.7]
Secondary
Change From Baseline in SGRQ-c Symptoms Score
SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Symptoms component consisted of questions 1 to 7 in Part 1. Symptoms score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in SGRQ-c Symptoms Score | -4.0 Scores on a scale | Standard Error 2.95 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in SGRQ-c Symptoms Score | -1.4 Scores on a scale | Standard Error 3.29 |
| Placebo- Male Participants | Change From Baseline in SGRQ-c Symptoms Score | -3.5 Scores on a scale | Standard Error 3.38 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in SGRQ-c Symptoms Score | -4.0 Scores on a scale | Standard Error 3.2 |
90% CI: [-5, 10.1]
90% CI: [-8.4, 7.5]
Secondary
Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP)
A bung size-specific to the participant was placed in the nostril deemed to be most patent by the investigator. The participant was asked to make a maximum voluntary sniff effort via a peak flow meter and the greatest effort from 10 repeat measurements were recorded. SnIP was measured in centimeter of water (cm H2O). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Days 56 and 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Day 56,n=21,19,21,21 | -6.0 centimeter of water | Standard Deviation 11.2 |
| Placebo- Female Participants | Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Day 90,n=20,18,18,20 | -0.7 centimeter of water | Standard Deviation 8.55 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Day 90,n=20,18,18,20 | -0.4 centimeter of water | Standard Deviation 11.34 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Day 56,n=21,19,21,21 | 3.4 centimeter of water | Standard Deviation 14.14 |
| Placebo- Male Participants | Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Day 56,n=21,19,21,21 | 0.7 centimeter of water | Standard Deviation 17.82 |
| Placebo- Male Participants | Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Day 90,n=20,18,18,20 | -1.2 centimeter of water | Standard Deviation 15.21 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Day 56,n=21,19,21,21 | -0.8 centimeter of water | Standard Deviation 15.51 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) | Day 90,n=20,18,18,20 | 2.5 centimeter of water | Standard Deviation 21.39 |
Secondary
Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer
Steps per day was assessed using an accelerometer, a clinically validated physical activity monitor which was used to measure the levels of physical activity. Participants wore an accelerometer for 7 days during individual timepoint. Values at Baseline, Day 56 and Day 90 were the average values collected from an accelerometer for 7 days after the Day -9, Day 56 and Day 90. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day -9), Days 56 and 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Day 56,n=17,14,14,17 | 285.19 Steps per day | Standard Deviation 1289.604 |
| Placebo- Female Participants | Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Day 90,n=17,17,14,14 | -246.45 Steps per day | Standard Deviation 756.414 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Day 90,n=17,17,14,14 | 786.21 Steps per day | Standard Deviation 1439.988 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Day 56,n=17,14,14,17 | 389.58 Steps per day | Standard Deviation 1322.701 |
| Placebo- Male Participants | Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Day 56,n=17,14,14,17 | 120.41 Steps per day | Standard Deviation 1282.092 |
| Placebo- Male Participants | Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Day 90,n=17,17,14,14 | -527.07 Steps per day | Standard Deviation 1077.747 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Day 56,n=17,14,14,17 | -17.40 Steps per day | Standard Deviation 1334.539 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer | Day 90,n=17,17,14,14 | 611.36 Steps per day | Standard Deviation 1499.559 |
Secondary
Change From Baseline in St. George Respiratory Questionnaire (SGRQ) for COPD (SGRQ-c) Total Score
SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Total score was calculated by summing the weight to all the positive responses in each component. Total score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in St. George Respiratory Questionnaire (SGRQ) for COPD (SGRQ-c) Total Score | -3.9 Scores on a scale | Standard Error 1.71 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in St. George Respiratory Questionnaire (SGRQ) for COPD (SGRQ-c) Total Score | -0.9 Scores on a scale | Standard Error 1.9 |
| Placebo- Male Participants | Change From Baseline in St. George Respiratory Questionnaire (SGRQ) for COPD (SGRQ-c) Total Score | -1.7 Scores on a scale | Standard Error 1.87 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in St. George Respiratory Questionnaire (SGRQ) for COPD (SGRQ-c) Total Score | 0.4 Scores on a scale | Standard Error 1.77 |
90% CI: [-1.4, 7.4]
90% CI: [-2.3, 6.5]
Secondary
Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 28
'Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 28
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 28 | -0.644 Seconds | Standard Error 0.6333 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 28 | -1.196 Seconds | Standard Error 0.6491 |
| Placebo- Male Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 28 | -0.464 Seconds | Standard Error 0.3841 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 28 | -0.537 Seconds | Standard Error 0.3763 |
90% CI: [-2.082, 0.977]
90% CI: [-0.977, 0.832]
Secondary
Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 56
'Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 56 | -1.207 Seconds | Standard Error 0.5912 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 56 | -2.023 Seconds | Standard Error 0.6124 |
| Placebo- Male Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 56 | -0.323 Seconds | Standard Error 0.5294 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 56 | -0.160 Seconds | Standard Error 0.5282 |
90% CI: [-2.252, 0.619]
90% CI: [-1.096, 1.422]
Secondary
Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 90
'Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 90 | -1.070 Seconds | Standard Error 0.6956 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 90 | -2.030 Seconds | Standard Error 0.7362 |
| Placebo- Male Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 90 | 1.144 Seconds | Standard Error 1.4013 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 90 | -0.793 Seconds | Standard Error 1.3401 |
90% CI: [-2.668, 0.748]
90% CI: [-5.208, 1.333]
Secondary
Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 28
''Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 28
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 28 | -0.236 Seconds | Standard Error 0.1132 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 28 | -0.277 Seconds | Standard Error 0.1161 |
| Placebo- Male Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 28 | -0.167 Seconds | Standard Error 0.1133 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 28 | -0.110 Seconds | Standard Error 0.1108 |
90% CI: [-0.314, 0.233]
90% CI: [-0.209, 0.324]
Secondary
Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 56
'Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 56 | 0.010 Seconds | Standard Error 0.1487 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 56 | -0.276 Seconds | Standard Error 0.156 |
| Placebo- Male Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 56 | -0.093 Seconds | Standard Error 0.1437 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 56 | -0.284 Seconds | Standard Error 0.1438 |
90% CI: [-0.65, 0.077]
90% CI: [-0.534, 0.152]
Secondary
Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 90
'Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 90 | -0.043 Seconds | Standard Error 0.2194 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 90 | -0.055 Seconds | Standard Error 0.2361 |
| Placebo- Male Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 90 | -0.130 Seconds | Standard Error 0.1331 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 90 | -0.360 Seconds | Standard Error 0.1275 |
90% CI: [-0.555, 0.532]
90% CI: [-0.541, 0.08]
Secondary
Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28
Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 28
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | -0.017 Kilograms | Standard Error 0.2004 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | 1.150 Kilograms | Standard Error 0.2106 |
| Placebo- Male Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | 0.075 Kilograms | Standard Error 0.3004 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 | 0.998 Kilograms | Standard Error 0.2869 |
90% CI: [0.677, 1.658]
90% CI: [0.222, 1.623]
Secondary
Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56
Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | -0.564 Kilograms | Standard Error 0.2372 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | 1.522 Kilograms | Standard Error 0.2587 |
| Placebo- Male Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | -0.373 Kilograms | Standard Error 0.382 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 | 1.327 Kilograms | Standard Error 0.37 |
90% CI: [1.493, 2.678]
90% CI: [0.801, 2.6]
Secondary
Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90
Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | -0.531 Kilograms | Standard Error 0.3349 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | 1.577 Kilograms | Standard Error 0.3666 |
| Placebo- Male Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | -0.424 Kilograms | Standard Error 0.5056 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 | 1.689 Kilograms | Standard Error 0.4666 |
90% CI: [1.271, 2.945]
90% CI: [0.949, 3.277]
Secondary
Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 28
Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores \<=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 28
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 28 | 0.3 Scores on a scale | Standard Error 0.25 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 28 | 0.4 Scores on a scale | Standard Error 0.26 |
| Placebo- Male Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 28 | 0.2 Scores on a scale | Standard Error 0.19 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 28 | 0.3 Scores on a scale | Standard Error 0.18 |
90% CI: [-0.6, 0.6]
90% CI: [-0.4, 0.5]
Secondary
Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 56
Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores \<=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 56
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 56 | 0.4 Scores on a scale | Standard Error 0.24 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 56 | 0.4 Scores on a scale | Standard Error 0.25 |
| Placebo- Male Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 56 | 0.1 Scores on a scale | Standard Error 0.24 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 56 | 0.4 Scores on a scale | Standard Error 0.24 |
90% CI: [-0.6, 0.6]
90% CI: [-0.2, 0.9]
Secondary
Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 90
Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores \<=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented.
Time frame: Baseline (Day 1, Pre-dose), Day 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 90 | 0.3 Scores on a scale | Standard Error 0.26 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 90 | 0.5 Scores on a scale | Standard Error 0.28 |
| Placebo- Male Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 90 | 0.4 Scores on a scale | Standard Error 0.23 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 90 | 0.5 Scores on a scale | Standard Error 0.22 |
90% CI: [-0.4, 0.9]
90% CI: [-0.5, 0.6]
Secondary
Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer
Vector magnitude unit per wear time was assessed using an accelerometer, a clinically validated physical activity monitor which was used to measure the levels of physical activity. Participants wore an accelerometer for 7 days during individual timepoint. Values at Baseline, Day 56 and Day 90 were the average values collected from accelerometer for 7 days after the Day -9, Day 56 and Day 90. Data from an accelerator was uploaded to a central site. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value.
Time frame: Baseline (Day -9), Days 56 and 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo- Female Participants | Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Day 56,n=17,14,14,17 | 9.19 Vector magnitude units per minute | Standard Deviation 82.596 |
| Placebo- Female Participants | Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Day 90,n=17,17,14,14 | -6.60 Vector magnitude units per minute | Standard Deviation 65.648 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Day 90,n=17,17,14,14 | 0.40 Vector magnitude units per minute | Standard Deviation 64.67 |
| GSK2881078 1.0 mg- Female Participants | Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Day 56,n=17,14,14,17 | -4.83 Vector magnitude units per minute | Standard Deviation 66.4 |
| Placebo- Male Participants | Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Day 56,n=17,14,14,17 | 56.42 Vector magnitude units per minute | Standard Deviation 86.284 |
| Placebo- Male Participants | Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Day 90,n=17,17,14,14 | -3.73 Vector magnitude units per minute | Standard Deviation 74.849 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Day 56,n=17,14,14,17 | 71.98 Vector magnitude units per minute | Standard Deviation 175.403 |
| GSK2881078 2.0 mg- Male Participants | Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer | Day 90,n=17,17,14,14 | 42.36 Vector magnitude units per minute | Standard Deviation 184.191 |
Secondary
Clearance (CL) of GSK2881078 Following Oral Dose in Participants
Blood samples were collected at designated timepoints. Pharmacokinetics (PK) parameters of GSK2881078 were calculated using non-compartmental methods.
Time frame: Day 14 (Pre-dose), Day 28 (Pre-dose and at 1 to 4 hours Post-dose), Day 56 (at 5 to 8 hours Post-dose), Day 90 (Pre-dose)
Population: Pharmacokinetic Population comprised of participants in the 'All Participants (all randomized participants who received at least one dose of study medication)'' Population for whom a PK sample was obtained and analyzed for GSK2881078.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Clearance (CL) of GSK2881078 Following Oral Dose in Participants | 0.393 Liters per hour | Geometric Coefficient of Variation 59.5 |
| GSK2881078 1.0 mg- Female Participants | Clearance (CL) of GSK2881078 Following Oral Dose in Participants | 0.476 Liters per hour | Geometric Coefficient of Variation 44 |
Secondary
Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time
Participant-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to assess the participant's impression of change in their disease severity since the beginning of the study. Responses to the PGIC question were on a 7 point Likert scale: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. Number of participants with PGIC score is presented by treatment group, visit and by 7 response categories.
Time frame: Days 14, 28, 56 and 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, much worse,n=21,20,23,23 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, better,n=21,18,18,20 | 3 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, worse,n=21,19,21,21 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, slightly better,n=21,20,23,23 | 7 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, much better,n=21,19,21,21 | 2 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, slightly worse,n=21,19,21,21 | 1 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, no change,n=21,19,21,21 | 2 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, much worse,n=21,19,21,21 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, better,n=21,19,21,21 | 10 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, slightly better,n=21,19,21,21 | 6 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, better,n=21,20,23,23 | 7 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, slightly better,n=21,18,18,20 | 7 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, much better,n=21,20,23,23 | 1 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, much better,n=21,18,18,20 | 1 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, much worse,n=21,20,21,22 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, slightly worse,n=21,20,23,23 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, no change,n=21,18,18,20 | 9 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, worse,n=21,20,21,22 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, slightly worse,n=21,20,21,22 | 1 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, slightly worse,n=21,18,18,20 | 1 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, no change,n=21,20,21,22 | 3 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, slightly better,n=21,20,21,22 | 9 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, no change,n=21,20,23,23 | 6 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, worse,n=21,18,18,20 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, better,n=21,20,21,22 | 5 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, much better,n=21,20,21,22 | 3 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, worse,n=21,20,23,23 | 0 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, much worse,n=21,18,18,20 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, better,n=21,18,18,20 | 4 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, much worse,n=21,19,21,21 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, much worse,n=21,20,21,22 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, much better,n=21,19,21,21 | 1 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, worse,n=21,18,18,20 | 1 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, worse,n=21,19,21,21 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, better,n=21,20,21,22 | 6 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, slightly better,n=21,20,21,22 | 6 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, worse,n=21,20,21,22 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, slightly worse,n=21,19,21,21 | 3 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, slightly better,n=21,20,23,23 | 7 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, better,n=21,19,21,21 | 6 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, slightly worse,n=21,20,23,23 | 1 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, no change,n=21,19,21,21 | 5 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, slightly worse,n=21,18,18,20 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, no change,n=21,20,23,23 | 5 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, slightly worse,n=21,20,21,22 | 2 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, slightly better,n=21,19,21,21 | 4 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, worse,n=21,20,23,23 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, slightly better,n=21,18,18,20 | 3 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, much better,n=21,18,18,20 | 2 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, better,n=21,20,23,23 | 5 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, much worse,n=21,20,23,23 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, much worse,n=21,18,18,20 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, much better,n=21,20,21,22 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, much better,n=21,20,23,23 | 2 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, no change,n=21,20,21,22 | 6 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, no change,n=21,18,18,20 | 8 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, no change,n=21,19,21,21 | 4 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, much worse,n=21,20,23,23 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, worse,n=21,20,23,23 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, slightly worse,n=21,20,23,23 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, no change,n=21,20,23,23 | 9 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, slightly better,n=21,20,23,23 | 4 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, better,n=21,20,23,23 | 8 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, much better,n=21,20,23,23 | 2 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, much worse,n=21,20,21,22 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, worse,n=21,20,21,22 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, slightly worse,n=21,20,21,22 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, no change,n=21,20,21,22 | 4 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, slightly better,n=21,20,21,22 | 10 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, better,n=21,20,21,22 | 5 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, much better,n=21,20,21,22 | 2 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, much worse,n=21,19,21,21 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, worse,n=21,19,21,21 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, slightly worse,n=21,19,21,21 | 1 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, slightly better,n=21,19,21,21 | 7 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, better,n=21,19,21,21 | 8 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, much better,n=21,19,21,21 | 1 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, much worse,n=21,18,18,20 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, worse,n=21,18,18,20 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, slightly worse,n=21,18,18,20 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, no change,n=21,18,18,20 | 5 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, slightly better,n=21,18,18,20 | 9 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, better,n=21,18,18,20 | 4 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, much better,n=21,18,18,20 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, much better,n=21,20,21,22 | 2 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, better,n=21,20,21,22 | 7 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, slightly worse,n=21,20,23,23 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, much worse,n=21,18,18,20 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, slightly better,n=21,20,21,22 | 7 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, no change,n=21,20,21,22 | 6 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, much better,n=21,18,18,20 | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, worse,n=21,18,18,20 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, slightly worse,n=21,20,21,22 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, worse,n=21,20,21,22 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, better,n=21,18,18,20 | 4 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, slightly worse,n=21,18,18,20 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 28, much worse,n=21,20,21,22 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, much better,n=21,20,23,23 | 2 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, worse,n=21,20,23,23 | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, no change,n=21,18,18,20 | 6 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, better,n=21,20,23,23 | 7 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, slightly better,n=21,20,23,23 | 4 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, much worse,n=21,20,23,23 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, slightly better,n=21,19,21,21 | 5 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, no change,n=21,19,21,21 | 5 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, slightly worse,n=21,19,21,21 | 4 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 90, slightly better,n=21,18,18,20 | 9 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, better,n=21,19,21,21 | 5 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, worse,n=21,19,21,21 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, much worse,n=21,19,21,21 | 0 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 14, no change,n=21,20,23,23 | 9 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time | Day 56, much better,n=21,19,21,21 | 2 Participants |
Secondary
Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time
PGRS is a single global question and was asked to participants to rate their COPD severity on a four point scale ranging from 1 to 4 (1=mild, 2=moderate, 3=severe, 4=very severe). Number of participants with PGRS score ranging from mild to very severe are presented over time.
Time frame: Days 1 and 90
Population: Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, mild,n=21,20,23,23 | 2 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, moderate,n=21,20,23,23 | 9 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, severe,n=21,20,23,23 | 8 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, very severe,n=21,20,23,23 | 2 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, mild,n=21,18,18,20 | 4 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, moderate,n=21,18,18,20 | 9 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, severe,n=21,18,18,20 | 6 Participants |
| Placebo- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, very severe,n=21,18,18,20 | 2 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, moderate,n=21,18,18,20 | 7 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, mild,n=21,18,18,20 | 4 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, moderate,n=21,20,23,23 | 13 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, very severe,n=21,18,18,20 | 1 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, severe,n=21,18,18,20 | 6 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, very severe,n=21,20,23,23 | 0 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, severe,n=21,20,23,23 | 7 Participants |
| GSK2881078 1.0 mg- Female Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, mild,n=21,20,23,23 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, severe,n=21,18,18,20 | 8 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, severe,n=21,20,23,23 | 12 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, very severe,n=21,20,23,23 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, mild,n=21,18,18,20 | 1 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, moderate,n=21,18,18,20 | 9 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, very severe,n=21,18,18,20 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, mild,n=21,20,23,23 | 0 Participants |
| Placebo- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, moderate,n=21,20,23,23 | 11 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, severe,n=21,20,23,23 | 8 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, very severe,n=21,20,23,23 | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, moderate,n=21,20,23,23 | 12 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 1, mild,n=21,20,23,23 | 2 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, mild,n=21,18,18,20 | 5 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, very severe,n=21,18,18,20 | 1 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, severe,n=21,18,18,20 | 12 Participants |
| GSK2881078 2.0 mg- Male Participants | Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time | Day 90, moderate,n=21,18,18,20 | 2 Participants |
Secondary
Volume of Distribution at Steady State (Vss) of GSK2881078 Following Oral Dose in Participants
Blood samples were collected at designated timepoints. PK parameters of GSK2881078 were calculated using non-compartmental methods.
Time frame: Day 14 (Pre-dose), Day 28 (Pre-dose and at 1 to 4 hours Post-dose), Day 56 (at 5 to 8 hours Post-dose), Day 90 (Pre-dose)
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo- Female Participants | Volume of Distribution at Steady State (Vss) of GSK2881078 Following Oral Dose in Participants | 39.4 Liters | Geometric Coefficient of Variation 16.3 |
| GSK2881078 1.0 mg- Female Participants | Volume of Distribution at Steady State (Vss) of GSK2881078 Following Oral Dose in Participants | 48.3 Liters | Geometric Coefficient of Variation 29.8 |