Gastroparesis
Conditions
Keywords
tolerability, pharmacokinetics, 13 C oral breath test, Type I and II Diabetes mellitus, gastroparesis, gut motility, phase II, pharmacodynamics, repeat dose, gastric emptying, symptoms, GSK962040
Brief summary
GSK962040 is a novel small molecule motilin agonist. The Phase I studies (MOT107043 and MOT109681) demonstrated that single doses of GSK962040 up to 150 mg and repeat dosing of up to 125 mg/day for 14 days were well tolerated with adverse events not occurring in greater prevalence than placebo, and no significant abnormal vital sign, ECG, or clinical laboratory findings. Pharmacokinetic parameters were linear and approximately dose proportional over the range of doses administered. Single doses of 50 mg - 150 mg GSK962040 significantly increased the rate of gastric emptying up to 40% as measured by the 13C octanoic acid stable isotope breath test. A similar effect of 50 mg and 125 mg on gastric emptying was observed throughout repeated dosing to healthy volunteers for 14-days. The aims of the present investigation (MOT114479) are to assess the pharmacodynamic effects (gastric emptying and symptoms), safety, tolerability, and pharmacokinetics of GSK962040 after 28 days of once-daily dosing in Type I and Type II diabetic subjects with gastroparesis. An additional aim is to characterize the dose/exposure - pharmacodynamic effect relationship.
Interventions
DRUGGSK962040 (5 mg tablet)
5 mg tablet
25 mg tablet
DRUGGSK962040 (125 mg tablet)
125 mg tablet
DRUGPlacebo
matching placebo tablet
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Type I or II Diabetes Mellitus (HbA1C \< 10%) * Male or female between 18 and 80 years of age, inclusive. * Patient has gastroparesis at screening (gastric half-time of emptying \> upper limit of normal as determined by 13C-oral breath test) * Patient must have a \> or = 3 month history of relevant symptoms of gastroparesis (e.g., chronic post-prandial fullness, early satiety, postprandial nausea), patients will have a mean of the daily scores over a minimum of 7 days indicating \> or = mild (2) and \< or = severe (4) post-prandial fullness assessed using the GCSI-DD during the screening period prior to randomization. * A female patient is eligible to participate if she is of: Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/mL, or a value consistent with the local laboratory standard value, is confirmatory. OR Child-bearing potential and agrees to use one of the contraception methods listed in Section 8.1 for an appropriate period of time (as determined by the product label or investigator) prior to the start of dosing to sufficiently minimize the risk of pregnancy at that point. Female patients must agree to use contraception for at least 5 days following the last dose of study medication. * Male patients must agree to use one of the contraception methods listed in Section 8.1. This criterion must be followed from the time of the first dose of study medication through at least 5 days after the last dose of study medication. * BMI \>18 and \< or = 35.0 kg/m2 (inclusive). * Patient has never had a gastrectomy, nor major gastric surgical procedure or any evidence of bowel obstruction or strictures within the previous 12 months * Dosage of any concomitant medications has been stable for at least 3 weeks, except for routine adjustments in daily insulin treatments. * Estimated (or measured) glomerular filtration rate \> or = 30 mL/min. * QTcB or QTcF \< 450 msec or QTc \< 480 msec in patients with Bundle Branch Block based on single or average QTc value of triplicate values obtained over a brief recording period. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * AST and ALT \< 2xULN; alkaline phosphatase and bilirubin \< or = 1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
Exclusion criteria
* Patient has acute severe gastroenteritis * Patient has a gastric pacemaker * Patient is on chronic parenteral feeding * Patient has pronounced dehydration * Recent (last 6 weeks) history of poor control of diabetes e.g. hypoglycaemia requiring medical intervention, diabetic ketoacidosis, admission for control diabetes or complications of diabetes * Patient has evidence of severe cardiovascular autonomic neuropathy (e.g. history of recurrent syncope in the last 6 months) * Patient has a history of eating disorders (anorexia nervosa, binge eating, bulimia) * Use of medications potentially influencing upper gastrointestinal motility or appetite within one week of the study (e.g., prokinetic drugs, macrolide antibiotics (erythromycin), GLP-1 mimetics) * Regular opiate use * Use of prohibited medications listed in Section 9.2 within the restricted timeframe relative to the first dose of study medication. * History or presence of clinically significant gastro-intestinal, hepatic or renal disease or other condition that would in the opinion of the investigator or medical monitor make the subject unsuitable for inclusion in this clinical study. * The patient has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). * 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 GSK Medical Monitor, contraindicates their participation. * Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day time-period. * Pregnant females as determined by positive serum or urine hCG test (from the first urine of the day) at screening or prior to dosing. * Lactating females. * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastric Half Emptying Time (GEt1/2) | Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28 | Gastric half emptying time is the time taken for half the contents of the stomach to empty. Gastric emptying was measured using the 13C-oral breath test, which is a tracer method that utilizes 13C, a non-radioactive isotope. Basal breath samples were obtained after an overnight fast or otherwise after 4 hours of fasting following a light meal. On Day 1 and Day 28, participants were then dosed with GSK962040 and additional breath test samples were taken prior to administration of a 13C-labelled test meal. The test meal was consumed approximately 80 minutes(min) later. After consumption of the test meal, breath samples were collected at pre-specified time points over an approximately 4 hour period following the test meal. For the duration of the breath test, no food or drink were allowed. The 13C breath content was determined by isotope ratio mass spectrometry. GE t1/2 was determined by using the cumulative percentage of the administered dose of 13C excreted in breath over 4 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | Baseline, Day 1, and Day 8 | Blood pressure measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The Baseline value was Day 1 Pre-Dose values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Baseline, Day 1, and Day 8 | Heart rate measurements were taken at pre-dose and 120 min (completion of meal) on Day 1 and Day 28. The Baseline value was Day 1 Pre-Dose values . Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Change From Baseline in Electrocardiography Parameters (12-lead ECG) | Baseline, Day 1 and Day 28 | ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 28. The Baseline value was the Day 1 pre-dose value. ECG parameters included PR interval, QRS duration, QT interval, QTcB, QTcF and RR interval. |
| Number of Participants Outside the Normal Range for SBP and DBP | Screening2/Baseline (Day -30 to -1), Day 1 and 28 | Blood pressure measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The clinical concern range (CCR) for SBP was greater than (\<) 85 and less than (\>) 160 and for DBP the range was \<45 and \>100. Data for semi-supine position has been presented. Baseline was Screening2/Baseline values. |
| Number of Participants Outside the Normal Range for Heart Rate | Screening2/Baseline (Day -30 to -1), Day 1 and 28 | Heart rate measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The CCR for heart rate was Increase or decrease by less than or equal to (\>=) 15 and \>= 30. Data for semi-supine position has been presented. Baseline was Screening2/Baseline values. |
| Number of Participants Outside the Normal Range for 12-lead ECG | Baseline (Day 1 pre-dose), Day 1, Day 14 and Day 28 | ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 28. The CCR for ECG parameters were: PR interval (\<110 and \>220), QRS interval (\<75 and \>110), Absolute QTc interval (\>450 to =\< 480) respectively. Baseline was the pre-dose reading for Day 1. Data for abnormal- clinically significant (ACS) and abnormal- not clinically significant (ANCS) has been presented. |
| Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28 | Alkaline phosphatase, alanine amino transferase, aspartate amino transferase, gamma glutamyl transferase, creatine kinase, lactate dehydrogenase measurements were taken at Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28 | Direct Bilirubin, Total Bilirubin, Creatinine, Uric acid measurements were taken at Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Baseline (Day 1 pre-dose) and Day 28 | Albumin, Total Protein measurements were taken at Baseline (Day 1 pre-dose), and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Baseline (Day 1 pre-dose) and Day 28 | Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon dioxide content/Bicarbonate measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Baseline (Day 1 pre-dose) and Day 28 | Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet count, White Blood cell count measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Mean Change From Baseline in Hematology Parameters : Hematocrit | Baseline (Day 1 pre-dose) and Day 28 | Hematocrit measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin | Baseline (Day 1 pre-dose) and Day 28 | Mean Corpuscle Hemoglobin measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Baseline (Day 1 pre-dose) and Day 28 | Hemoglobin, Mean Corpuscle Hemoglobin concentration measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Up to follow-up (5-10 days post last dose) | An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Data for on-treatment adverse events is reported. |
| Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Baseline (Day 1 pre-dose) and Day 28 | Red Blood Cell count, Reticulocytes measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points | Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28 | AUC(0-t) was derived from GSK962040 plasma concentration-time data. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.Only participants who received GSK962040 drug were analyzed. |
| Maximum Observed Concentration (Cmax) at Specified Time Points | Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28 | Cmax is defined as the maximum observed drug concentration after administration. Cmax was determined directly from the raw concentration-time data. Samples were collected at the following times: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose. |
| Time of Occurrence of Cmax (Tmax) at Specified Time Points | Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28 | Tmax is defined as the time to reach the observed maximum concentration. Samples were collected at the following times: Tmax was determined directly from the raw concentration-time data. Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose. |
| Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points | Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28 | Analysis of pre-dose (trough) concentration at the end of the dosing interval (Ct) was planned to be performed from the samples collected at Pre -dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28. |
| Apparent Clearance Following Oral Dosing (CL/F) at Specified Time Points | Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28 | CL/F was calculated as dose/AUC. The parameter was planned to be analyzed from samples collected at Pre -dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however the data for this outcome measure was not collected. |
| Apparent Volume of Distribution (V/F) at Specified Time Points | Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28 | The apparent volume of distribution V/F = CL/F × MRT, where MRT is the mean residence time. The parameter was planned to be analyzed using samples collected at Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however, the data for this outcome measure was not collected. |
| Apparent Terminal Elimination Half-life (t1/2) at Specified Time Points | The parameter was planned to be analyzed using samples collected at Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however, the data for this outcome measure was not collected. | This outcome measure was not analyzed in results. |
| Time to First Bowel Movement After First Dose | Up to Day 28 | The time to first bowel movement was calculated as the time of the first bowel movement after the first dose in hours (floored) for each participant. If a participant had fewer than 5 days worth of data then the daily mean for that week was set to missing for the following two parameters: Bowel Movement Count and Stool Consistency. Seventeen participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics of time to first bowel movement. |
| Daily Bowel Movement Frequency | Up to Week 4 (Day 28) | Daily bowel movement frequency analyzed number of times passed stools in 24 hours of duration. Following dosing with study medication, stool monitoring was performed up to Day 28. Seventeen participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics. |
| Daily Average Stool Consistency | Up to Week 4 (Day 28) | Stool consistency was determined on a scale of 1 to 5 (1 = Very hard, 2 = Hard, 3 = Formed, 4 = Loose, 5 = Watery). Following dosing with study medication, stool monitoring was performed up to Day 28. Participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics. |
| Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Up to 14 days post last dose (Day 28) | GCSI-DD was measured on a 6-point scale. The Total GCSI-DD score was the mean of the following three subscales: Nausea/Vomiting Subscale = mean (nausea, retching, vomiting), Fullness/Early Satiety Subscale = mean (feeling excessively full after meals, not able to finish a normal-sized meal, stomach fullness, loss of appetite), Bloating Subscale = mean (bloating, stomach or belly visibly larger). Each subscale was scored on a severity scale of 0 (none) to 5 (very severe), with lower scores representing less symptom severity. The change from Baseline to each study week in average score was derived and if it improved by 1 point or more, that participant was defined as responder for that symptom and on that particular week. Baseline was Screening2/Baseline values (Day -30 to -1). Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Baseline(Screening i.e., Day -30 to -1), Day 1 and 28 | WMC is an ingestible telemetric capsule which measures pH, pressure and temperature to assess total gastric emptying time, small and large bowel transit time, colonic transit time, and whole gut transit time. The WMC was ingested immediately following the standard test meal for the oral breath test. Data was collected on a data logger, which was worn on a belt clip. The WMC passed naturally in the participant's stools between 2 and 5 days after ingestion. The parameters Whole bowel transit time, 100 % gastric emptying time (truncated at 240 minutes), small bowel transit time, colonic transit time were analyzed. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
| Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume | Baseline (Day 1 pre-dose) and Day 28 | Mean Corpuscle Volume measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value. |
Countries
Australia, Belgium, Canada, Sweden, United Kingdom, United States
Participant flow
Recruitment details
A total of 80 participants were enrolled and randomized from 03 May 2011 to 26 Feb 2013. The study was conducted at 22 centers, 1 center in Australia, 1 center in Sweden, 2 centers in Belgium, 4 centers in Canada, 5 Centers in United Kingdom and 9 centers in United States.
Pre-assignment details
Out of 80 participants randomized, 1 participant withdrew consent prior to dosing in GSK962040 50 milligram (mg) arm. Remaining 79 participants were included in All subject population
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo tablets matching to GSK962040 administered orally once daily for a period of 28 days. | 21 |
| GSK962040 10 mg Participants received GSK962040 10 mg tablets administered orally once daily for a period of 28 days. | 18 |
| GSK962040 50 mg Participants received GSK962040 50 mg tablets administered orally once daily for a period of 28 days. | 18 |
| GSK962040 125 mg Participants received GSK962040 125 mg tablets administered orally once daily for a period of 28 days. | 22 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | GSK962040 125 mg | GSK962040 50 mg | GSK962040 10 mg |
|---|---|---|---|---|---|
| Age, Continuous | 54.6 Years STANDARD_DEVIATION 14.23 | 53.7 Years STANDARD_DEVIATION 12.22 | 51.4 Years STANDARD_DEVIATION 11.34 | 55.2 Years STANDARD_DEVIATION 12.17 | 54.0 Years STANDARD_DEVIATION 11.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 71 Participants | 20 Participants | 17 Participants | 15 Participants |
| Sex: Female, Male Female | 14 Participants | 47 Participants | 9 Participants | 10 Participants | 14 Participants |
| Sex: Female, Male Male | 7 Participants | 32 Participants | 13 Participants | 8 Participants | 4 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 / 21 | 0 / 18 | 0 / 18 | 0 / 22 |
| other Total, other adverse events | 11 / 21 | 14 / 18 | 14 / 18 | 14 / 22 |
| serious Total, serious adverse events | 1 / 21 | 0 / 18 | 1 / 18 | 0 / 22 |
Outcome results
Primary
Gastric Half Emptying Time (GEt1/2)
Gastric half emptying time is the time taken for half the contents of the stomach to empty. Gastric emptying was measured using the 13C-oral breath test, which is a tracer method that utilizes 13C, a non-radioactive isotope. Basal breath samples were obtained after an overnight fast or otherwise after 4 hours of fasting following a light meal. On Day 1 and Day 28, participants were then dosed with GSK962040 and additional breath test samples were taken prior to administration of a 13C-labelled test meal. The test meal was consumed approximately 80 minutes(min) later. After consumption of the test meal, breath samples were collected at pre-specified time points over an approximately 4 hour period following the test meal. For the duration of the breath test, no food or drink were allowed. The 13C breath content was determined by isotope ratio mass spectrometry. GE t1/2 was determined by using the cumulative percentage of the administered dose of 13C excreted in breath over 4 hours.
Time frame: Screening2/Baseline (Day -30 to -1) , Day 1, and Day 28
Population: The 'All Subjects Population' compromised of all participants who received at least one dose of study medication. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Gastric Half Emptying Time (GEt1/2) | Baseline | 131.2 Minutes | Standard Deviation 25.31 |
| Placebo | Gastric Half Emptying Time (GEt1/2) | Day 28 | 111.8 Minutes | Standard Deviation 24.37 |
| Placebo | Gastric Half Emptying Time (GEt1/2) | Day 1 | 124.1 Minutes | Standard Deviation 39.25 |
| GSK962040 10 mg | Gastric Half Emptying Time (GEt1/2) | Baseline | 106.5 Minutes | Standard Deviation 23.42 |
| GSK962040 10 mg | Gastric Half Emptying Time (GEt1/2) | Day 28 | 111.8 Minutes | Standard Deviation 32.23 |
| GSK962040 10 mg | Gastric Half Emptying Time (GEt1/2) | Day 1 | 106.6 Minutes | Standard Deviation 27.07 |
| GSK962040 50 mg | Gastric Half Emptying Time (GEt1/2) | Day 1 | 104.8 Minutes | Standard Deviation 21.61 |
| GSK962040 50 mg | Gastric Half Emptying Time (GEt1/2) | Baseline | 118.2 Minutes | Standard Deviation 31.13 |
| GSK962040 50 mg | Gastric Half Emptying Time (GEt1/2) | Day 28 | 107.9 Minutes | Standard Deviation 29.03 |
| GSK962040 125 mg | Gastric Half Emptying Time (GEt1/2) | Baseline | 131.1 Minutes | Standard Deviation 32.66 |
| GSK962040 125 mg | Gastric Half Emptying Time (GEt1/2) | Day 28 | 117.8 Minutes | Standard Deviation 44.2 |
| GSK962040 125 mg | Gastric Half Emptying Time (GEt1/2) | Day 1 | 99.4 Minutes | Standard Deviation 33.55 |
Comparison: GSK962040 10 mg versus Placebo Day 195% CI: [-21.96, 15.24]
Comparison: GSK962040 50 mg versus Placebo Day 195% CI: [-30.01, 6.4]
Comparison: GSK962040 125 mg versus Placebo Day 195% CI: [-42.99, -8.32]
Comparison: GSK962040 10 mg versus Placebo Day 2895% CI: [-5.06, 34.53]
Comparison: GSK962040 50 mg vs Placebo Day 2895% CI: [-14.64, 23.08]
Comparison: GSK962040 125 mg versus Placebo Day 2895% CI: [-11.18, 24.47]
Comparison: Day 28 versus Day 1 of the Placebo arm95% CI: [-28.73, 2.9]
Comparison: Day 28 versus Day 1 of GSK962040 10 mg arm95% CI: [-11.69, 22.05]
Comparison: Day 28 versus Day 1 of GSK962040 50 mg arm95% CI: [-13.13, 19.36]
Comparison: Day 28 versus Day 1 of GSK962040 125 mg arm95% CI: [4.47, 34.3]
Comparison: Type 1 Diabetes, Day 195% CI: [-0.32, -0.129]Mixed Models Analysis
Comparison: Type 1 Diabetes, Day 2895% CI: [-0.171, 0.016]Mixed Models Analysis
Comparison: Type 2 Diabetes, Day 195% CI: [-0.32, -0.129]Mixed Models Analysis
Comparison: Type 2 Diabetes, Day 2895% CI: [-0.171, 0.016]Mixed Models Analysis
Secondary
Apparent Clearance Following Oral Dosing (CL/F) at Specified Time Points
CL/F was calculated as dose/AUC. The parameter was planned to be analyzed from samples collected at Pre -dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however the data for this outcome measure was not collected.
Time frame: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Population: PK Population. The data for this outcome measure was not collected.
Secondary
Apparent Terminal Elimination Half-life (t1/2) at Specified Time Points
This outcome measure was not analyzed in results.
Time frame: The parameter was planned to be analyzed using samples collected at Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however, the data for this outcome measure was not collected.
Population: PK Population. The data for this outcome measure was not collected.
Secondary
Apparent Volume of Distribution (V/F) at Specified Time Points
The apparent volume of distribution V/F = CL/F × MRT, where MRT is the mean residence time. The parameter was planned to be analyzed using samples collected at Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28, however, the data for this outcome measure was not collected.
Time frame: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Population: PK Population. The data for this outcome measure was not collected.
Secondary
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points
AUC(0-t) was derived from GSK962040 plasma concentration-time data. AUC was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.Only participants who received GSK962040 drug were analyzed.
Time frame: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Population: The 'Pharmacokinetic (PK) Population' was defined as participants in the 'All subjects' population for whom a PK sample was obtained and analyzed. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points | Day 1 | 854.9 Nanograms.hour/milliliter (ng.h/mL) | Geometric Coefficient of Variation 36.6 |
| Placebo | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points | Day 28 | 1908.1 Nanograms.hour/milliliter (ng.h/mL) | Geometric Coefficient of Variation 46.1 |
| GSK962040 10 mg | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points | Day 1 | 4083.1 Nanograms.hour/milliliter (ng.h/mL) | Geometric Coefficient of Variation 23.6 |
| GSK962040 10 mg | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points | Day 28 | 7347.2 Nanograms.hour/milliliter (ng.h/mL) | Geometric Coefficient of Variation 24.3 |
| GSK962040 50 mg | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points | Day 1 | 12911.9 Nanograms.hour/milliliter (ng.h/mL) | Geometric Coefficient of Variation 30 |
| GSK962040 50 mg | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration AUC(0-t) at Specified Time Points | Day 28 | 22173.3 Nanograms.hour/milliliter (ng.h/mL) | Geometric Coefficient of Variation 31.8 |
Secondary
Change From Baseline in Electrocardiography Parameters (12-lead ECG)
ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 28. The Baseline value was the Day 1 pre-dose value. ECG parameters included PR interval, QRS duration, QT interval, QTcB, QTcF and RR interval.
Time frame: Baseline, Day 1 and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 28 pre-dose | 2.4 Milliseconds (msec) | Standard Deviation 4.93 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 14 pre-dose | -5.5 Milliseconds (msec) | Standard Deviation 7.39 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 28 pre-dose | 2.4 Milliseconds (msec) | Standard Deviation 17.12 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 28 1.5 hours | 1.2 Milliseconds (msec) | Standard Deviation 14.28 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 1 1.5 hours | 0.2 Milliseconds (msec) | Standard Deviation 5.18 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 14 pre-dose | 0.1 Milliseconds (msec) | Standard Deviation 5.26 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 1 1.5 hours | -2.6 Milliseconds (msec) | Standard Deviation 10.4 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 28 1.5 hours | 0.8 Milliseconds (msec) | Standard Deviation 4.29 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 1 1.5 hours | 1.0 Milliseconds (msec) | Standard Deviation 12.3 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 14 pre-dose | -8.8 Milliseconds (msec) | Standard Deviation 18.52 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 28 pre-dose | 0.3 Milliseconds (msec) | Standard Deviation 21.83 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 28 1.5 hours | 4.9 Milliseconds (msec) | Standard Deviation 16.37 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 1 1.5 hours | -2.84 Milliseconds (msec) | Standard Deviation 13.906 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 14 pre-dose | 3.23 Milliseconds (msec) | Standard Deviation 11.503 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 28 pre-dose | -3.85 Milliseconds (msec) | Standard Deviation 20.907 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 28 1.5 hours | 1.59 Milliseconds (msec) | Standard Deviation 24.246 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 1 1.5 hours | -1.52 Milliseconds (msec) | Standard Deviation 12.089 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 14 pre-dose | -1.02 Milliseconds (msec) | Standard Deviation 11.942 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 28 pre-dose | -2.55 Milliseconds (msec) | Standard Deviation 18.782 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 28 1.5 hours | 2.70 Milliseconds (msec) | Standard Deviation 20.473 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 1 1.5 hours | 16.82 Milliseconds (msec) | Standard Deviation 56.084 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 14 pre-dose | -54.61 Milliseconds (msec) | Standard Deviation 76.965 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 28 pre-dose | 18.15 Milliseconds (msec) | Standard Deviation 109.227 |
| Placebo | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 28 1.5 hours | 13.96 Milliseconds (msec) | Standard Deviation 76.906 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 28 1.5 hours | -23.69 Milliseconds (msec) | Standard Deviation 96.568 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 1 1.5 hours | -1.94 Milliseconds (msec) | Standard Deviation 13.721 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 28 1.5 hours | 0.5 Milliseconds (msec) | Standard Deviation 11.48 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 28 pre-dose | -31.14 Milliseconds (msec) | Standard Deviation 75.74 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 14 pre-dose | -33.95 Milliseconds (msec) | Standard Deviation 75.539 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 14 pre-dose | -2.97 Milliseconds (msec) | Standard Deviation 12.075 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 1 1.5 hours | -0.2 Milliseconds (msec) | Standard Deviation 17.45 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 1 1.5 hours | -1.26 Milliseconds (msec) | Standard Deviation 14.709 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 14 pre-dose | -0.8 Milliseconds (msec) | Standard Deviation 4.33 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 28 pre-dose | 2.71 Milliseconds (msec) | Standard Deviation 9.741 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 28 pre-dose | -7.1 Milliseconds (msec) | Standard Deviation 26.93 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 28 1.5 hours | 1.86 Milliseconds (msec) | Standard Deviation 14.682 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 1 1.5 hours | 7.26 Milliseconds (msec) | Standard Deviation 44.025 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 14 pre-dose | -9.6 Milliseconds (msec) | Standard Deviation 19.11 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 28 1.5 hours | -0.24 Milliseconds (msec) | Standard Deviation 14.344 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 14 pre-dose | 0.6 Milliseconds (msec) | Standard Deviation 7.87 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 28 1.5 hours | 0.6 Milliseconds (msec) | Standard Deviation 3.98 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 28 pre-dose | -5.0 Milliseconds (msec) | Standard Deviation 21.36 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 28 pre-dose | 1.1 Milliseconds (msec) | Standard Deviation 4.54 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 28 pre-dose | 0.04 Milliseconds (msec) | Standard Deviation 12.835 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 1 1.5 hours | 3.2 Milliseconds (msec) | Standard Deviation 7.46 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 28 1.5 hours | -2.8 Milliseconds (msec) | Standard Deviation 22.18 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 1 1.5 hours | -0.6 Milliseconds (msec) | Standard Deviation 4.16 |
| GSK962040 10 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 14 pre-dose | -5.57 Milliseconds (msec) | Standard Deviation 12.599 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 28 pre-dose | -2.0 Milliseconds (msec) | Standard Deviation 23.2 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 28 pre-dose | -0.3 Milliseconds (msec) | Standard Deviation 3.84 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 28 1.5 hours | -0.3 Milliseconds (msec) | Standard Deviation 4.96 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 1 1.5 hours | -3.8 Milliseconds (msec) | Standard Deviation 13.16 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 14 pre-dose | -10.7 Milliseconds (msec) | Standard Deviation 25.58 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 1 1.5 hours | -3.26 Milliseconds (msec) | Standard Deviation 68.824 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 28 1.5 hours | -0.64 Milliseconds (msec) | Standard Deviation 16.857 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 28 1.5 hours | -1.3 Milliseconds (msec) | Standard Deviation 26.49 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 1 1.5 hours | -2.45 Milliseconds (msec) | Standard Deviation 13.447 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 14 pre-dose | -2.68 Milliseconds (msec) | Standard Deviation 18.41 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 14 pre-dose | -42.92 Milliseconds (msec) | Standard Deviation 90.333 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 28 pre-dose | 1.31 Milliseconds (msec) | Standard Deviation 18.419 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 28 1.5 hours | -0.16 Milliseconds (msec) | Standard Deviation 17.208 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 28 1.5 hours | -4.08 Milliseconds (msec) | Standard Deviation 114.019 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 1 1.5 hours | -2.84 Milliseconds (msec) | Standard Deviation 11.08 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 14 pre-dose | -5.91 Milliseconds (msec) | Standard Deviation 19.109 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 28 pre-dose | -3.31 Milliseconds (msec) | Standard Deviation 99.049 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 1 1.5 hours | 0.5 Milliseconds (msec) | Standard Deviation 13.03 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 14 pre-dose | -1.6 Milliseconds (msec) | Standard Deviation 11.29 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 28 pre-dose | 0.96 Milliseconds (msec) | Standard Deviation 15.942 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 28 pre-dose | 2.2 Milliseconds (msec) | Standard Deviation 18.32 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 28 1.5 hours | 3.6 Milliseconds (msec) | Standard Deviation 16.71 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 1 1.5 hours | 0.1 Milliseconds (msec) | Standard Deviation 4.07 |
| GSK962040 50 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 14 pre-dose | -0.1 Milliseconds (msec) | Standard Deviation 3.57 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 28 pre-dose | -11.51 Milliseconds (msec) | Standard Deviation 108.68 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 1 1.5 hours | 8.74 Milliseconds (msec) | Standard Deviation 81.926 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 28 1.5 hours | 0.0 Milliseconds (msec) | Standard Deviation 4.97 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 1 1.5 hours | -0.9 Milliseconds (msec) | Standard Deviation 9.68 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 28 pre-dose | -3.0 Milliseconds (msec) | Standard Deviation 20.29 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 14 pre-dose | -9.6 Milliseconds (msec) | Standard Deviation 19.87 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 14 pre-dose | -0.9 Milliseconds (msec) | Standard Deviation 4.97 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 14 pre-dose | -3.1 Milliseconds (msec) | Standard Deviation 9.25 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 1 1.5 hours | 0.6 Milliseconds (msec) | Standard Deviation 5.22 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 1 1.5 hours | 1.6 Milliseconds (msec) | Standard Deviation 12.64 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 28 1.5 hours | -2.17 Milliseconds (msec) | Standard Deviation 12.797 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 28 pre-dose | -0.1 Milliseconds (msec) | Standard Deviation 8.14 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 14 pre-dose | -35.25 Milliseconds (msec) | Standard Deviation 102.822 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 28 pre-dose | -0.20 Milliseconds (msec) | Standard Deviation 15.062 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 28 pre-dose | -1.21 Milliseconds (msec) | Standard Deviation 12.49 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 28 1.5 hours | -0.88 Milliseconds (msec) | Standard Deviation 15.216 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | RR interval Day 28 1.5 hours | -15.60 Milliseconds (msec) | Standard Deviation 108.056 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 14 pre-dose | -1.42 Milliseconds (msec) | Standard Deviation 16.245 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QRS duration Day 28 pre-dose | 1.0 Milliseconds (msec) | Standard Deviation 4.81 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 1 1.5 hours | 0.72 Milliseconds (msec) | Standard Deviation 12.418 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcB Day 1 1.5 hours | -0.12 Milliseconds (msec) | Standard Deviation 15.771 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QT interval Day 28 1.5 hours | -4.5 Milliseconds (msec) | Standard Deviation 21.38 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | PR interval Day 28 1.5 hours | -4.3 Milliseconds (msec) | Standard Deviation 9.54 |
| GSK962040 125 mg | Change From Baseline in Electrocardiography Parameters (12-lead ECG) | QTcF Day 14 pre-dose | -4.37 Milliseconds (msec) | Standard Deviation 13.314 |
Secondary
Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position
Heart rate measurements were taken at pre-dose and 120 min (completion of meal) on Day 1 and Day 28. The Baseline value was Day 1 Pre-Dose values . Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline, Day 1, and Day 8
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Heart rate Day 1 3.5 hours | -0.3 Beats per minute (BPM) | Standard Deviation 7.6 |
| Placebo | Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Heart rate Day 28 3.5 hours | -3.9 Beats per minute (BPM) | Standard Deviation 6.86 |
| GSK962040 10 mg | Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Heart rate Day 28 3.5 hours | -1.5 Beats per minute (BPM) | Standard Deviation 6.94 |
| GSK962040 10 mg | Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Heart rate Day 1 3.5 hours | -0.8 Beats per minute (BPM) | Standard Deviation 6.64 |
| GSK962040 50 mg | Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Heart rate Day 1 3.5 hours | -0.3 Beats per minute (BPM) | Standard Deviation 8.39 |
| GSK962040 50 mg | Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Heart rate Day 28 3.5 hours | 1.0 Beats per minute (BPM) | Standard Deviation 9.09 |
| GSK962040 125 mg | Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Heart rate Day 1 3.5 hours | 2.1 Beats per minute (BPM) | Standard Deviation 6.31 |
| GSK962040 125 mg | Change From Baseline in Heart Rate at Specified Time Points in Semi-supine Position | Heart rate Day 28 3.5 hours | 0.7 Beats per minute (BPM) | Standard Deviation 8.26 |
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position
Blood pressure measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The Baseline value was Day 1 Pre-Dose values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline, Day 1, and Day 8
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | SBP Day 1 3.5 hours | 0.6 Millimeters of mercury (mmHg) | Standard Deviation 13.68 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | SBP Day 28 3.5 hours | 3.2 Millimeters of mercury (mmHg) | Standard Deviation 12.09 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | DBP Day 1 3.5 hours | -2.5 Millimeters of mercury (mmHg) | Standard Deviation 8.09 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | DBP Day 28 3.5 hours | -0.3 Millimeters of mercury (mmHg) | Standard Deviation 4.69 |
| GSK962040 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | SBP Day 28 3.5 hours | -1.1 Millimeters of mercury (mmHg) | Standard Deviation 15.56 |
| GSK962040 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | DBP Day 1 3.5 hours | 1.1 Millimeters of mercury (mmHg) | Standard Deviation 7.45 |
| GSK962040 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | DBP Day 28 3.5 hours | -0.8 Millimeters of mercury (mmHg) | Standard Deviation 8.62 |
| GSK962040 10 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | SBP Day 1 3.5 hours | -1.8 Millimeters of mercury (mmHg) | Standard Deviation 17.5 |
| GSK962040 50 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | DBP Day 1 3.5 hours | -0.7 Millimeters of mercury (mmHg) | Standard Deviation 8.5 |
| GSK962040 50 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | SBP Day 28 3.5 hours | 4.6 Millimeters of mercury (mmHg) | Standard Deviation 16.47 |
| GSK962040 50 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | DBP Day 28 3.5 hours | 2.7 Millimeters of mercury (mmHg) | Standard Deviation 6.33 |
| GSK962040 50 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | SBP Day 1 3.5 hours | 0.8 Millimeters of mercury (mmHg) | Standard Deviation 18.07 |
| GSK962040 125 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | DBP Day 28 3.5 hours | -6.1 Millimeters of mercury (mmHg) | Standard Deviation 7.32 |
| GSK962040 125 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | SBP Day 28 3.5 hours | -7.2 Millimeters of mercury (mmHg) | Standard Deviation 11.62 |
| GSK962040 125 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | SBP Day 1 3.5 hours | -2.3 Millimeters of mercury (mmHg) | Standard Deviation 8.85 |
| GSK962040 125 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure(DBP) at Specified Time Points in Semi-supine Position | DBP Day 1 3.5 hours | -2.3 Millimeters of mercury (mmHg) | Standard Deviation 5.19 |
Secondary
Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD)
GCSI-DD was measured on a 6-point scale. The Total GCSI-DD score was the mean of the following three subscales: Nausea/Vomiting Subscale = mean (nausea, retching, vomiting), Fullness/Early Satiety Subscale = mean (feeling excessively full after meals, not able to finish a normal-sized meal, stomach fullness, loss of appetite), Bloating Subscale = mean (bloating, stomach or belly visibly larger). Each subscale was scored on a severity scale of 0 (none) to 5 (very severe), with lower scores representing less symptom severity. The change from Baseline to each study week in average score was derived and if it improved by 1 point or more, that participant was defined as responder for that symptom and on that particular week. Baseline was Screening2/Baseline values (Day -30 to -1). Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Up to 14 days post last dose (Day 28)
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 1 | -0.48 Score on a scale | Standard Deviation 0.645 |
| Placebo | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 2 | -0.68 Score on a scale | Standard Deviation 0.728 |
| Placebo | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 3 | -0.75 Score on a scale | Standard Deviation 0.77 |
| Placebo | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 4 | -0.86 Score on a scale | Standard Deviation 1.001 |
| Placebo | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 5 | -0.87 Score on a scale | Standard Deviation 0.951 |
| Placebo | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 6 | -0.85 Score on a scale | Standard Deviation 0.943 |
| GSK962040 10 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 6 | -0.96 Score on a scale | Standard Deviation 1 |
| GSK962040 10 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 4 | -1.32 Score on a scale | Standard Deviation 0.98 |
| GSK962040 10 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 1 | -0.46 Score on a scale | Standard Deviation 0.676 |
| GSK962040 10 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 3 | -1.29 Score on a scale | Standard Deviation 0.936 |
| GSK962040 10 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 2 | -1.04 Score on a scale | Standard Deviation 1.062 |
| GSK962040 10 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 5 | -1.19 Score on a scale | Standard Deviation 0.906 |
| GSK962040 50 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 2 | -1.21 Score on a scale | Standard Deviation 0.663 |
| GSK962040 50 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 3 | -1.16 Score on a scale | Standard Deviation 0.745 |
| GSK962040 50 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 4 | -1.12 Score on a scale | Standard Deviation 0.67 |
| GSK962040 50 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 6 | -0.86 Score on a scale | Standard Deviation 0.632 |
| GSK962040 50 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 5 | -1.07 Score on a scale | Standard Deviation 0.738 |
| GSK962040 50 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 1 | -0.58 Score on a scale | Standard Deviation 0.379 |
| GSK962040 125 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 5 | -0.74 Score on a scale | Standard Deviation 0.728 |
| GSK962040 125 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 6 | -0.59 Score on a scale | Standard Deviation 0.776 |
| GSK962040 125 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 2 | -0.72 Score on a scale | Standard Deviation 0.597 |
| GSK962040 125 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 4 | -0.82 Score on a scale | Standard Deviation 0.727 |
| GSK962040 125 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 1 | -0.57 Score on a scale | Standard Deviation 0.491 |
| GSK962040 125 mg | Change From Baseline in Upper Gastrointestinal (GI) Symptoms as Assessed by Total Gastrointestinal Cardinal Symptom Index - Daily Diary (GCSI-DD) | Week 3 | -0.77 Score on a scale | Standard Deviation 0.654 |
Secondary
Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC)
WMC is an ingestible telemetric capsule which measures pH, pressure and temperature to assess total gastric emptying time, small and large bowel transit time, colonic transit time, and whole gut transit time. The WMC was ingested immediately following the standard test meal for the oral breath test. Data was collected on a data logger, which was worn on a belt clip. The WMC passed naturally in the participant's stools between 2 and 5 days after ingestion. The parameters Whole bowel transit time, 100 % gastric emptying time (truncated at 240 minutes), small bowel transit time, colonic transit time were analyzed. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline(Screening i.e., Day -30 to -1), Day 1 and 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time Day 1 | -159.9 minutes | Standard Deviation 616.67 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time Day 28 | -243.0 minutes | Standard Deviation 500.49 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time(Truncated) Day 1 | 2.7 minutes | Standard Deviation 27.95 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time(Truncated) Day 28 | -10.7 minutes | Standard Deviation 18.6 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Colonic Transit Time Day 1 | -331.3 minutes | Standard Deviation 1349.11 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Colonic Transit Time Day 28 | -518.1 minutes | Standard Deviation 2650.06 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Small Bowel Transit Time Day 1 | -24.5 minutes | Standard Deviation 118.39 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Small Bowel Transit Time 28 | -76.4 minutes | Standard Deviation 107.89 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Whole Bowel Transit Time Day 1 | -527.6 minutes | Standard Deviation 1489.02 |
| Placebo | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Whole Bowel Transit Time 28 | -777.6 minutes | Standard Deviation 2644.8 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time(Truncated) Day 1 | 3.7 minutes | Standard Deviation 28.87 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Whole Bowel Transit Time Day 1 | -402.1 minutes | Standard Deviation 2109.06 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time(Truncated) Day 28 | 19.7 minutes | Standard Deviation 42.47 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Colonic Transit Time Day 1 | -92.9 minutes | Standard Deviation 1970.38 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Colonic Transit Time Day 28 | 142.9 minutes | Standard Deviation 1326.2 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Small Bowel Transit Time Day 1 | -47.7 minutes | Standard Deviation 94.33 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Whole Bowel Transit Time 28 | -2.4 minutes | Standard Deviation 1298.37 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Small Bowel Transit Time 28 | -57.3 minutes | Standard Deviation 176.42 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time Day 1 | -240.3 minutes | Standard Deviation 567.18 |
| GSK962040 10 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time Day 28 | -15.4 minutes | Standard Deviation 502.8 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Small Bowel Transit Time 28 | -7.1 minutes | Standard Deviation 148.51 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Small Bowel Transit Time Day 1 | 15.7 minutes | Standard Deviation 211.88 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Whole Bowel Transit Time 28 | -233.5 minutes | Standard Deviation 1850.91 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time Day 1 | -323.8 minutes | Standard Deviation 461.05 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time(Truncated) Day 28 | -13.9 minutes | Standard Deviation 42.34 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Colonic Transit Time Day 28 | -29.4 minutes | Standard Deviation 1702.69 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Whole Bowel Transit Time Day 1 | -493.1 minutes | Standard Deviation 1987.51 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time Day 28 | -162.7 minutes | Standard Deviation 558.96 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Colonic Transit Time Day 1 | -170.5 minutes | Standard Deviation 1723.01 |
| GSK962040 50 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time(Truncated) Day 1 | -15.8 minutes | Standard Deviation 61.32 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Colonic Transit Time Day 1 | -598.3 minutes | Standard Deviation 1617.05 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Small Bowel Transit Time 28 | -28.6 minutes | Standard Deviation 135.44 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Colonic Transit Time Day 28 | -416.4 minutes | Standard Deviation 1447.79 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Whole Bowel Transit Time 28 | -789.1 minutes | Standard Deviation 1560.06 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Small Bowel Transit Time Day 1 | -6.6 minutes | Standard Deviation 149.11 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time Day 28 | -341.3 minutes | Standard Deviation 599.52 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time(Truncated) Day 1 | -65.5 minutes | Standard Deviation 91.11 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time(Truncated) Day 28 | -40.2 minutes | Standard Deviation 68.66 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | 100% Gastric Emptying Time Day 1 | -381.0 minutes | Standard Deviation 541.73 |
| GSK962040 125 mg | Change From Baseline in Whole Bowel Transit Time, 100 % Gastric Emptying Time (Truncated at 240 Minutes), Small Bowel Transit Time, Colonic Transit Time as Determined by Wireless Motility Capsule (WMC) | Whole Bowel Transit Time Day 1 | -1002.5 minutes | Standard Deviation 2045.6 |
Secondary
Daily Average Stool Consistency
Stool consistency was determined on a scale of 1 to 5 (1 = Very hard, 2 = Hard, 3 = Formed, 4 = Loose, 5 = Watery). Following dosing with study medication, stool monitoring was performed up to Day 28. Participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics.
Time frame: Up to Week 4 (Day 28)
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Daily Average Stool Consistency | Week 3 | 2.89 Bowel Movements/ 24 hours | Standard Deviation 0.517 |
| Placebo | Daily Average Stool Consistency | Week 4 | 2.92 Bowel Movements/ 24 hours | Standard Deviation 0.528 |
| Placebo | Daily Average Stool Consistency | Week 2 | 2.98 Bowel Movements/ 24 hours | Standard Deviation 0.73 |
| Placebo | Daily Average Stool Consistency | Week 1 | 2.91 Bowel Movements/ 24 hours | Standard Deviation 0.817 |
| GSK962040 10 mg | Daily Average Stool Consistency | Week 2 | 2.81 Bowel Movements/ 24 hours | Standard Deviation 0.673 |
| GSK962040 10 mg | Daily Average Stool Consistency | Week 1 | 3.24 Bowel Movements/ 24 hours | Standard Deviation 0.524 |
| GSK962040 10 mg | Daily Average Stool Consistency | Week 3 | 2.87 Bowel Movements/ 24 hours | Standard Deviation 0.889 |
| GSK962040 10 mg | Daily Average Stool Consistency | Week 4 | 2.96 Bowel Movements/ 24 hours | Standard Deviation 0.625 |
| GSK962040 50 mg | Daily Average Stool Consistency | Week 4 | 2.98 Bowel Movements/ 24 hours | Standard Deviation 0.502 |
| GSK962040 50 mg | Daily Average Stool Consistency | Week 1 | 2.80 Bowel Movements/ 24 hours | Standard Deviation 0.815 |
| GSK962040 50 mg | Daily Average Stool Consistency | Week 2 | 3.05 Bowel Movements/ 24 hours | Standard Deviation 0.798 |
| GSK962040 50 mg | Daily Average Stool Consistency | Week 3 | 2.99 Bowel Movements/ 24 hours | Standard Deviation 0.558 |
| GSK962040 125 mg | Daily Average Stool Consistency | Week 3 | 3.26 Bowel Movements/ 24 hours | Standard Deviation 0.683 |
| GSK962040 125 mg | Daily Average Stool Consistency | Week 2 | 3.29 Bowel Movements/ 24 hours | Standard Deviation 0.724 |
| GSK962040 125 mg | Daily Average Stool Consistency | Week 1 | 3.71 Bowel Movements/ 24 hours | Standard Deviation 0.874 |
| GSK962040 125 mg | Daily Average Stool Consistency | Week 4 | 3.37 Bowel Movements/ 24 hours | Standard Deviation 0.569 |
Secondary
Daily Bowel Movement Frequency
Daily bowel movement frequency analyzed number of times passed stools in 24 hours of duration. Following dosing with study medication, stool monitoring was performed up to Day 28. Seventeen participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics.
Time frame: Up to Week 4 (Day 28)
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Daily Bowel Movement Frequency | Week 3 | 2.18 Bowel movements/24 hours | Standard Deviation 3.269 |
| Placebo | Daily Bowel Movement Frequency | Week 2 | 2.23 Bowel movements/24 hours | Standard Deviation 3.473 |
| Placebo | Daily Bowel Movement Frequency | Week 1 | 1.30 Bowel movements/24 hours | Standard Deviation 0.872 |
| Placebo | Daily Bowel Movement Frequency | Week 4 | 2.11 Bowel movements/24 hours | Standard Deviation 3.432 |
| GSK962040 10 mg | Daily Bowel Movement Frequency | Week 2 | 1.59 Bowel movements/24 hours | Standard Deviation 0.948 |
| GSK962040 10 mg | Daily Bowel Movement Frequency | Week 1 | 1.33 Bowel movements/24 hours | Standard Deviation 0.812 |
| GSK962040 10 mg | Daily Bowel Movement Frequency | Week 3 | 1.44 Bowel movements/24 hours | Standard Deviation 0.83 |
| GSK962040 10 mg | Daily Bowel Movement Frequency | Week 4 | 1.54 Bowel movements/24 hours | Standard Deviation 0.841 |
| GSK962040 50 mg | Daily Bowel Movement Frequency | Week 1 | 1.50 Bowel movements/24 hours | Standard Deviation 0.943 |
| GSK962040 50 mg | Daily Bowel Movement Frequency | Week 3 | 1.77 Bowel movements/24 hours | Standard Deviation 1.172 |
| GSK962040 50 mg | Daily Bowel Movement Frequency | Week 2 | 1.55 Bowel movements/24 hours | Standard Deviation 1.012 |
| GSK962040 50 mg | Daily Bowel Movement Frequency | Week 4 | 1.68 Bowel movements/24 hours | Standard Deviation 1.049 |
| GSK962040 125 mg | Daily Bowel Movement Frequency | Week 2 | 1.45 Bowel movements/24 hours | Standard Deviation 0.883 |
| GSK962040 125 mg | Daily Bowel Movement Frequency | Week 3 | 1.38 Bowel movements/24 hours | Standard Deviation 0.77 |
| GSK962040 125 mg | Daily Bowel Movement Frequency | Week 4 | 1.37 Bowel movements/24 hours | Standard Deviation 0.831 |
| GSK962040 125 mg | Daily Bowel Movement Frequency | Week 1 | 1.39 Bowel movements/24 hours | Standard Deviation 0.729 |
Secondary
Maximum Observed Concentration (Cmax) at Specified Time Points
Cmax is defined as the maximum observed drug concentration after administration. Cmax was determined directly from the raw concentration-time data. Samples were collected at the following times: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose.
Time frame: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Population: PK population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Concentration (Cmax) at Specified Time Points | Day 1 | 70.21 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 54.7 |
| Placebo | Maximum Observed Concentration (Cmax) at Specified Time Points | Day 28 | 131.71 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 52.9 |
| GSK962040 10 mg | Maximum Observed Concentration (Cmax) at Specified Time Points | Day 1 | 385.73 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.6 |
| GSK962040 10 mg | Maximum Observed Concentration (Cmax) at Specified Time Points | Day 28 | 530.97 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| GSK962040 50 mg | Maximum Observed Concentration (Cmax) at Specified Time Points | Day 1 | 1239.62 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| GSK962040 50 mg | Maximum Observed Concentration (Cmax) at Specified Time Points | Day 28 | 1703.29 Nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
Secondary
Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein
Albumin, Total Protein measurements were taken at Baseline (Day 1 pre-dose), and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Albumin Day 28 | -0.68 Grams per liter (g/L) | Standard Deviation 2.335 |
| Placebo | Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Total Protein Day 28 | -0.3 Grams per liter (g/L) | Standard Deviation 3.79 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Total Protein Day 28 | 0.7 Grams per liter (g/L) | Standard Deviation 2.94 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Albumin Day 28 | 0.49 Grams per liter (g/L) | Standard Deviation 2.04 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Albumin Day 28 | 0.11 Grams per liter (g/L) | Standard Deviation 1.323 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Total Protein Day 28 | 1.0 Grams per liter (g/L) | Standard Deviation 2.68 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Albumin Day 28 | -0.66 Grams per liter (g/L) | Standard Deviation 2.308 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Albumin, Total Protein | Total Protein Day 28 | -0.5 Grams per liter (g/L) | Standard Deviation 4.53 |
Secondary
Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase
Alkaline phosphatase, alanine amino transferase, aspartate amino transferase, gamma glutamyl transferase, creatine kinase, lactate dehydrogenase measurements were taken at Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 14 | 2.6 International units per liter (IU/L) | Standard Deviation 5.5 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 10 | 0.5 International units per liter (IU/L) | Standard Deviation 9.08 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 10 | 0.6 International units per liter (IU/L) | Standard Deviation 7.86 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 21 | -0.3 International units per liter (IU/L) | Standard Deviation 5.11 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 5 | -0.3 International units per liter (IU/L) | Standard Deviation 5.68 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 28 | -1.5 International units per liter (IU/L) | Standard Deviation 5.39 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 14 | 2.4 International units per liter (IU/L) | Standard Deviation 7.32 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 14 | 3.7 International units per liter (IU/L) | Standard Deviation 9.17 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 21 | -0.4 International units per liter (IU/L) | Standard Deviation 6.74 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Creatine Kinase Day 28 | -4.3 International units per liter (IU/L) | Standard Deviation 61.05 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 14 | -0.2 International units per liter (IU/L) | Standard Deviation 4.57 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 5 | 3.0 International units per liter (IU/L) | Standard Deviation 7.54 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 21 | 4.3 International units per liter (IU/L) | Standard Deviation 15.25 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 10 | 2.7 International units per liter (IU/L) | Standard Deviation 8.63 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 10 | -1.1 International units per liter (IU/L) | Standard Deviation 2.88 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 5 | -0.5 International units per liter (IU/L) | Standard Deviation 2.43 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 28 | 1.1 International units per liter (IU/L) | Standard Deviation 14.05 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Lactate Dehydrogenase Day 28 | -11.5 International units per liter (IU/L) | Standard Deviation 38.69 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 28 | -0.8 International units per liter (IU/L) | Standard Deviation 6.63 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 21 | -1.1 International units per liter (IU/L) | Standard Deviation 6.8 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 5 | 0.7 International units per liter (IU/L) | Standard Deviation 3.28 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 28 | -1.7 International units per liter (IU/L) | Standard Deviation 5.44 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 10 | 0.5 International units per liter (IU/L) | Standard Deviation 4.16 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 5 | 4.3 International units per liter (IU/L) | Standard Deviation 7.2 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 10 | 5.0 International units per liter (IU/L) | Standard Deviation 7.79 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 14 | 5.0 International units per liter (IU/L) | Standard Deviation 8.16 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 21 | 3.9 International units per liter (IU/L) | Standard Deviation 9.19 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 28 | 3.1 International units per liter (IU/L) | Standard Deviation 7.17 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 5 | 2.6 International units per liter (IU/L) | Standard Deviation 7.31 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 10 | 2.5 International units per liter (IU/L) | Standard Deviation 6.6 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 14 | 2.9 International units per liter (IU/L) | Standard Deviation 6.99 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 21 | 0.3 International units per liter (IU/L) | Standard Deviation 6.09 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 28 | 1.1 International units per liter (IU/L) | Standard Deviation 6.22 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 5 | 0.1 International units per liter (IU/L) | Standard Deviation 6.73 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 10 | 1.2 International units per liter (IU/L) | Standard Deviation 8.27 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 14 | -1.1 International units per liter (IU/L) | Standard Deviation 6.94 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 21 | -0.3 International units per liter (IU/L) | Standard Deviation 6.78 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 28 | 0.4 International units per liter (IU/L) | Standard Deviation 5.41 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 5 | 1.8 International units per liter (IU/L) | Standard Deviation 4.35 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 14 | 0.4 International units per liter (IU/L) | Standard Deviation 3.1 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 21 | -1.3 International units per liter (IU/L) | Standard Deviation 5 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 28 | 0.5 International units per liter (IU/L) | Standard Deviation 5.51 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Creatine Kinase Day 28 | 41.9 International units per liter (IU/L) | Standard Deviation 74.29 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Lactate Dehydrogenase Day 28 | 8.6 International units per liter (IU/L) | Standard Deviation 31.1 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 10 | 1.8 International units per liter (IU/L) | Standard Deviation 7.09 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 14 | -2.8 International units per liter (IU/L) | Standard Deviation 11.35 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 14 | 0.7 International units per liter (IU/L) | Standard Deviation 8.7 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 28 | -2.5 International units per liter (IU/L) | Standard Deviation 14.66 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 14 | 2.1 International units per liter (IU/L) | Standard Deviation 6.55 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Lactate Dehydrogenase Day 28 | -5.8 International units per liter (IU/L) | Standard Deviation 42.29 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 28 | -2.7 International units per liter (IU/L) | Standard Deviation 9.13 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 5 | 4.0 International units per liter (IU/L) | Standard Deviation 9.27 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 21 | 1.8 International units per liter (IU/L) | Standard Deviation 3.52 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 28 | 0.3 International units per liter (IU/L) | Standard Deviation 4.37 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 14 | -1.0 International units per liter (IU/L) | Standard Deviation 6.94 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 5 | 2.8 International units per liter (IU/L) | Standard Deviation 10.88 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 21 | -0.1 International units per liter (IU/L) | Standard Deviation 5.89 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Creatine Kinase Day 28 | 42.0 International units per liter (IU/L) | Standard Deviation 103.49 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 5 | 1.6 International units per liter (IU/L) | Standard Deviation 6.26 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 10 | 2.8 International units per liter (IU/L) | Standard Deviation 10.58 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 28 | -1.2 International units per liter (IU/L) | Standard Deviation 6.88 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 10 | -2.7 International units per liter (IU/L) | Standard Deviation 10.67 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 10 | -1.2 International units per liter (IU/L) | Standard Deviation 4.93 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 21 | 1.7 International units per liter (IU/L) | Standard Deviation 11.39 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 5 | -1.9 International units per liter (IU/L) | Standard Deviation 9.9 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 21 | -1.2 International units per liter (IU/L) | Standard Deviation 9.55 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 5 | 1.6 International units per liter (IU/L) | Standard Deviation 4.56 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 10 | 2.8 International units per liter (IU/L) | Standard Deviation 3.43 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 28 | 4.2 International units per liter (IU/L) | Standard Deviation 16.01 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 14 | 1.0 International units per liter (IU/L) | Standard Deviation 6.36 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 28 | -1.7 International units per liter (IU/L) | Standard Deviation 25.23 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 5 | -1.1 International units per liter (IU/L) | Standard Deviation 23.56 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 21 | 1.6 International units per liter (IU/L) | Standard Deviation 5.12 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Aspartate Amino Transferase Day 28 | 0.5 International units per liter (IU/L) | Standard Deviation 6.61 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 21 | -1.7 International units per liter (IU/L) | Standard Deviation 26.96 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 5 | 2.4 International units per liter (IU/L) | Standard Deviation 8.44 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 14 | -4.3 International units per liter (IU/L) | Standard Deviation 24.67 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 10 | 1.2 International units per liter (IU/L) | Standard Deviation 6.79 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Creatine Kinase Day 28 | 0.2 International units per liter (IU/L) | Standard Deviation 42.14 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 14 | 1.5 International units per liter (IU/L) | Standard Deviation 8.95 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alkaline Phosphatase Day 10 | -1.3 International units per liter (IU/L) | Standard Deviation 26.28 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 14 | -3.2 International units per liter (IU/L) | Standard Deviation 15.94 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Gamma Glutamyl Transferase Day 21 | 2.6 International units per liter (IU/L) | Standard Deviation 7.93 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 21 | -2.9 International units per liter (IU/L) | Standard Deviation 14.59 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 10 | -1.1 International units per liter (IU/L) | Standard Deviation 17.05 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 28 | -4.0 International units per liter (IU/L) | Standard Deviation 13.6 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Lactate Dehydrogenase Day 28 | -16.2 International units per liter (IU/L) | Standard Deviation 40.37 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Gamma Glutamyl Transferase, Creatine Kinase, Lactate Dehydrogenase | Alanine Amino Transferase Day 5 | -1.1 International units per liter (IU/L) | Standard Deviation 16.03 |
Secondary
Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate
Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon dioxide content/Bicarbonate measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Calcium Day 28 | -0.018 Millimoles per liter (MMOL/L) | Standard Deviation 0.1067 |
| Placebo | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Urea/BUN Day 28 | -0.35 Millimoles per liter (MMOL/L) | Standard Deviation 2.021 |
| Placebo | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Sodium Day 28 | -0.42 Millimoles per liter (MMOL/L) | Standard Deviation 3.203 |
| Placebo | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Chloride Day 28 | 0.26 Millimoles per liter (MMOL/L) | Standard Deviation 3.754 |
| Placebo | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Carbon dioxide content/Bicarbonate Day 28 | -0.21 Millimoles per liter (MMOL/L) | Standard Deviation 1.843 |
| Placebo | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Glucose Day 28 | -0.21 Millimoles per liter (MMOL/L) | Standard Deviation 4.343 |
| Placebo | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Potassium Day 28 | -0.042 Millimoles per liter (MMOL/L) | Standard Deviation 0.3564 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Urea/BUN Day 28 | -0.31 Millimoles per liter (MMOL/L) | Standard Deviation 1.778 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Potassium Day 28 | 0.094 Millimoles per liter (MMOL/L) | Standard Deviation 0.6002 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Glucose Day 28 | 0.24 Millimoles per liter (MMOL/L) | Standard Deviation 3.638 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Sodium Day 28 | -0.41 Millimoles per liter (MMOL/L) | Standard Deviation 2.303 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Carbon dioxide content/Bicarbonate Day 28 | -0.79 Millimoles per liter (MMOL/L) | Standard Deviation 2.286 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Chloride Day 28 | -0.93 Millimoles per liter (MMOL/L) | Standard Deviation 3.137 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Calcium Day 28 | -0.017 Millimoles per liter (MMOL/L) | Standard Deviation 0.0764 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Potassium Day 28 | -0.111 Millimoles per liter (MMOL/L) | Standard Deviation 0.5132 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Calcium Day 28 | 0.027 Millimoles per liter (MMOL/L) | Standard Deviation 0.0666 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Chloride Day 28 | -0.94 Millimoles per liter (MMOL/L) | Standard Deviation 2.578 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Glucose Day 28 | 0.66 Millimoles per liter (MMOL/L) | Standard Deviation 6.79 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Sodium Day 28 | -0.56 Millimoles per liter (MMOL/L) | Standard Deviation 2.833 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Urea/BUN Day 28 | -0.04 Millimoles per liter (MMOL/L) | Standard Deviation 1.942 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Carbon dioxide content/Bicarbonate Day 28 | 1.17 Millimoles per liter (MMOL/L) | Standard Deviation 2.526 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Glucose Day 28 | -0.25 Millimoles per liter (MMOL/L) | Standard Deviation 2.332 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Carbon dioxide content/Bicarbonate Day 28 | -0.08 Millimoles per liter (MMOL/L) | Standard Deviation 2.298 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Urea/BUN Day 28 | 0.26 Millimoles per liter (MMOL/L) | Standard Deviation 2.016 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Chloride Day 28 | 0.15 Millimoles per liter (MMOL/L) | Standard Deviation 2.759 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Calcium Day 28 | -0.031 Millimoles per liter (MMOL/L) | Standard Deviation 0.1323 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Sodium Day 28 | 0.00 Millimoles per liter (MMOL/L) | Standard Deviation 1.718 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry : Calcium, Chloride, Glucose, Potassium, Sodium, Urea/BUN, Carbon Dioxide Content/Bicarbonate | Potassium Day 28 | -0.068 Millimoles per liter (MMOL/L) | Standard Deviation 0.3999 |
Secondary
Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid
Direct Bilirubin, Total Bilirubin, Creatinine, Uric acid measurements were taken at Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose), Day 5, 10, 14, 21 and 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 14 | 0.5 Unit moles per litre (UMOL/L) | Standard Deviation 2.41 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin, Day 28 | 0.0 Unit moles per litre (UMOL/L) | Standard Deviation 1.87 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 10 | -0.4 Unit moles per litre (UMOL/L) | Standard Deviation 2.25 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 21 | 0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.75 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 21 | -0.6 Unit moles per litre (UMOL/L) | Standard Deviation 2.53 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 10 | 0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.75 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Creatinine Day 28 | -2.91 Unit moles per litre (UMOL/L) | Standard Deviation 6.156 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 28 | 0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.74 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 5 | 0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.75 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Uric acid Day 28 | -8.61 Unit moles per litre (UMOL/L) | Standard Deviation 39.359 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 14 | 0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.57 |
| Placebo | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 5 | 0.2 Unit moles per litre (UMOL/L) | Standard Deviation 2.43 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 14 | 0.1 Unit moles per litre (UMOL/L) | Standard Deviation 1.19 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 21 | 0.4 Unit moles per litre (UMOL/L) | Standard Deviation 3.72 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 14 | 0.2 Unit moles per litre (UMOL/L) | Standard Deviation 2.99 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 10 | 0.0 Unit moles per litre (UMOL/L) | Standard Deviation 1.65 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 5 | 0.4 Unit moles per litre (UMOL/L) | Standard Deviation 2.71 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 5 | -0.2 Unit moles per litre (UMOL/L) | Standard Deviation 1.27 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Creatinine Day 28 | 0.51 Unit moles per litre (UMOL/L) | Standard Deviation 7.415 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 21 | 0.2 Unit moles per litre (UMOL/L) | Standard Deviation 1.35 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 10 | -0.1 Unit moles per litre (UMOL/L) | Standard Deviation 3.13 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 28 | 0.3 Unit moles per litre (UMOL/L) | Standard Deviation 1.57 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Uric acid Day 28 | 3.56 Unit moles per litre (UMOL/L) | Standard Deviation 32.183 |
| GSK962040 10 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin, Day 28 | 1.2 Unit moles per litre (UMOL/L) | Standard Deviation 3.45 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 14 | -2.1 Unit moles per litre (UMOL/L) | Standard Deviation 3.15 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 10 | -1.8 Unit moles per litre (UMOL/L) | Standard Deviation 4.83 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 5 | -0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.62 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 10 | -0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.75 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 14 | -0.2 Unit moles per litre (UMOL/L) | Standard Deviation 0.7 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 21 | -0.2 Unit moles per litre (UMOL/L) | Standard Deviation 0.9 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 28 | 0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.98 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 5 | -2.6 Unit moles per litre (UMOL/L) | Standard Deviation 3.41 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 21 | -1.2 Unit moles per litre (UMOL/L) | Standard Deviation 3.49 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin, Day 28 | -0.6 Unit moles per litre (UMOL/L) | Standard Deviation 2.71 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Creatinine Day 28 | 9.42 Unit moles per litre (UMOL/L) | Standard Deviation 17.103 |
| GSK962040 50 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Uric acid Day 28 | 8.62 Unit moles per litre (UMOL/L) | Standard Deviation 25.412 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 5 | -0.5 Unit moles per litre (UMOL/L) | Standard Deviation 3.19 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 28 | -0.1 Unit moles per litre (UMOL/L) | Standard Deviation 0.84 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 5 | -0.0 Unit moles per litre (UMOL/L) | Standard Deviation 1.38 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin, Day 28 | -0.9 Unit moles per litre (UMOL/L) | Standard Deviation 3.27 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 21 | 0.1 Unit moles per litre (UMOL/L) | Standard Deviation 1.03 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 14 | -0.0 Unit moles per litre (UMOL/L) | Standard Deviation 1.21 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Uric acid Day 28 | 18.29 Unit moles per litre (UMOL/L) | Standard Deviation 39.987 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Creatinine Day 28 | 9.80 Unit moles per litre (UMOL/L) | Standard Deviation 11.993 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 14 | -0.3 Unit moles per litre (UMOL/L) | Standard Deviation 2.99 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 10 | -0.4 Unit moles per litre (UMOL/L) | Standard Deviation 2.57 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Direct Bilirubin Day 10 | -0.0 Unit moles per litre (UMOL/L) | Standard Deviation 1.1 |
| GSK962040 125 mg | Mean Change From Baseline in Clinical Chemistry: Direct Bilirubin, Total Bilirubin, Creatinine, Uric Acid | Total Bilirubin Day 21 | -0.2 Unit moles per litre (UMOL/L) | Standard Deviation 1.99 |
Secondary
Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count
Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet count, White Blood cell count measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Basophils Day 28 | 0.0066 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.03852 |
| Placebo | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Platelet count Day 28 | 6.4 Giga (10^9) cells per liter (GI/L) | Standard Deviation 32.76 |
| Placebo | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Total Neutrophils Day 28 | 0.1380 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.78256 |
| Placebo | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Eosinophils Day 28 | -0.0167 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.07137 |
| Placebo | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | White Blood cell count Day 28 | 0.144 Giga (10^9) cells per liter (GI/L) | Standard Deviation 1.0951 |
| Placebo | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Lymphocytes Day 28 | 0.0485 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.44972 |
| Placebo | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Monocytes Day 28 | -0.0327 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.16668 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Platelet count Day 28 | 1.5 Giga (10^9) cells per liter (GI/L) | Standard Deviation 35.37 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Monocytes Day 28 | -0.0530 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.09965 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Lymphocytes Day 28 | -0.0561 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.45151 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Total Neutrophils Day 28 | 0.2159 Giga (10^9) cells per liter (GI/L) | Standard Deviation 1.28307 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | White Blood cell count Day 28 | 0.225 Giga (10^9) cells per liter (GI/L) | Standard Deviation 1.4369 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Eosinophils Day 28 | 0.0431 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.11412 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Basophils Day 28 | -0.0388 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.09539 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Monocytes Day 28 | -0.0097 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.17272 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Basophils Day 28 | -0.0322 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.07998 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Eosinophils Day 28 | -0.0040 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.18975 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Lymphocytes Day 28 | 0.1887 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.31662 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Total Neutrophils Day 28 | 0.2949 Giga (10^9) cells per liter (GI/L) | Standard Deviation 1.20093 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Platelet count Day 28 | 0.6 Giga (10^9) cells per liter (GI/L) | Standard Deviation 28.87 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | White Blood cell count Day 28 | 0.428 Giga (10^9) cells per liter (GI/L) | Standard Deviation 1.011 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Lymphocytes Day 28 | -0.0099 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.34075 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | White Blood cell count Day 28 | -0.730 Giga (10^9) cells per liter (GI/L) | Standard Deviation 2.0794 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Platelet count Day 28 | -2.0 Giga (10^9) cells per liter (GI/L) | Standard Deviation 21.58 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Eosinophils Day 28 | 0.1173 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.41877 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Basophils Day 28 | 0.1072 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.43592 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Total Neutrophils Day 28 | -0.7640 Giga (10^9) cells per liter (GI/L) | Standard Deviation 1.97899 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (Total ANC - Total Absolute Neutrophil Count), Platelet Count, White Blood Cell Count | Monocytes Day 28 | -0.0298 Giga (10^9) cells per liter (GI/L) | Standard Deviation 0.10623 |
Secondary
Mean Change From Baseline in Hematology Parameters : Hematocrit
Hematocrit measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Hematology Parameters : Hematocrit | -0.0025 Ratio | Standard Deviation 0.01692 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Hematocrit | 0.0021 Ratio | Standard Deviation 0.01053 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Hematocrit | 0.0019 Ratio | Standard Deviation 0.01508 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Hematocrit | -0.0059 Ratio | Standard Deviation 0.01637 |
Secondary
Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration
Hemoglobin, Mean Corpuscle Hemoglobin concentration measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Hemoglobin Day 28 | 0.4 g/L | Standard Deviation 5.36 |
| Placebo | Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Mean Corpuscle Hemoglobin concentration Day 28 | 2.8 g/L | Standard Deviation 6.2 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Mean Corpuscle Hemoglobin concentration Day 28 | 1.6 g/L | Standard Deviation 4.92 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Hemoglobin Day 28 | 1.1 g/L | Standard Deviation 4.63 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Hemoglobin Day 28 | -0.2 g/L | Standard Deviation 5.46 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Mean Corpuscle Hemoglobin concentration Day 28 | -2.8 g/L | Standard Deviation 6.53 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Hemoglobin Day 28 | -2.7 g/L | Standard Deviation 5.11 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Hemoglobin, Mean Corpuscle Hemoglobin Concentration | Mean Corpuscle Hemoglobin concentration Day 28 | -1.9 g/L | Standard Deviation 7.81 |
Secondary
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin
Mean Corpuscle Hemoglobin measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin | 0.05 Picograms (Pg) | Standard Deviation 0.521 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin | 0.15 Picograms (Pg) | Standard Deviation 0.454 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin | -0.15 Picograms (Pg) | Standard Deviation 0.667 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Hemoglobin | -0.14 Picograms (Pg) | Standard Deviation 0.643 |
Secondary
Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume
Mean Corpuscle Volume measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume | -0.52 Femtoliters (FL) | Standard Deviation 0.952 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume | -0.24 Femtoliters (FL) | Standard Deviation 1.163 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume | 0.43 Femtoliters (FL) | Standard Deviation 1.514 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Mean Corpuscle Volume | 0.13 Femtoliters (FL) | Standard Deviation 1.318 |
Secondary
Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes
Red Blood Cell count, Reticulocytes measurements were taken at Baseline (Day 1 pre-dose) and Day 28. The Baseline value was the Day 1 pre-dose value. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Red Blood Cell count Day 28 | 0.003 Tera (10^12) cells per liter (TI/L) | Standard Deviation 0.2015 |
| Placebo | Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Reticulocytes Day 28 | -0.0080 Tera (10^12) cells per liter (TI/L) | Standard Deviation 0.02949 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Reticulocytes Day 28 | -0.0051 Tera (10^12) cells per liter (TI/L) | Standard Deviation 0.01418 |
| GSK962040 10 mg | Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Red Blood Cell count Day 28 | 0.035 Tera (10^12) cells per liter (TI/L) | Standard Deviation 0.1399 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Red Blood Cell count Day 28 | 0.003 Tera (10^12) cells per liter (TI/L) | Standard Deviation 0.1597 |
| GSK962040 50 mg | Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Reticulocytes Day 28 | 0.0070 Tera (10^12) cells per liter (TI/L) | Standard Deviation 0.01919 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Red Blood Cell count Day 28 | -0.072 Tera (10^12) cells per liter (TI/L) | Standard Deviation 0.166 |
| GSK962040 125 mg | Mean Change From Baseline in Hematology Parameters : Red Blood Cell Count, Reticulocytes | Reticulocytes Day 28 | -0.0050 Tera (10^12) cells per liter (TI/L) | Standard Deviation 0.01937 |
Secondary
Number of Participants Outside the Normal Range for 12-lead ECG
ECG measurements were taken at pre-dose and 0 min (completion of meal) on Day 1 and Day 28. The CCR for ECG parameters were: PR interval (\<110 and \>220), QRS interval (\<75 and \>110), Absolute QTc interval (\>450 to =\< 480) respectively. Baseline was the pre-dose reading for Day 1. Data for abnormal- clinically significant (ACS) and abnormal- not clinically significant (ANCS) has been presented.
Time frame: Baseline (Day 1 pre-dose), Day 1, Day 14 and Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 1.5 hour ANCS | 6 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 1.5 hour ANCS | 7 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 14 pre-dose ANCS | 7 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 pre-dose ACS | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 1.5 hour ACS | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 pre-dose ACS | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 pre-dose ANCS | 6 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 1.5 hour ACS | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 14 pre-dose ACS | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 pre-dose ANCS | 7 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 1.5 hour ACS | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 1.5 hour ANCS | 6 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 1.5 hour ACS | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 1.5 hour ANCS | 8 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 pre-dose ANCS | 7 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 pre-dose ACS | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 14 pre-dose ANCS | 7 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 14 pre-dose ACS | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 pre-dose ANCS | 5 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 pre-dose ACS | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 pre-dose ACS | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 1.5 hour ACS | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 pre-dose ANCS | 4 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 14 pre-dose ACS | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 1.5 hour ANCS | 5 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 pre-dose ACS | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 1.5 hour ACS | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 pre-dose ANCS | 6 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 1.5 hour ANCS | 6 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 14 pre-dose ANCS | 5 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 1.5 hour ACS | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 pre-dose ANCS | 5 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 pre-dose ACS | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 1.5 hour ANCS | 6 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 1 1.5 hour ACS | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 14 pre-dose ANCS | 7 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 14 pre-dose ACS | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 pre-dose ANCS | 5 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 pre-dose ACS | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for 12-lead ECG | Day 28 1.5 hour ANCS | 5 Participants |
Secondary
Number of Participants Outside the Normal Range for Heart Rate
Heart rate measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The CCR for heart rate was Increase or decrease by less than or equal to (\>=) 15 and \>= 30. Data for semi-supine position has been presented. Baseline was Screening2/Baseline values.
Time frame: Screening2/Baseline (Day -30 to -1), Day 1 and 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Screening 3.5 hours <CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Screening 3.5 hours >CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 1 3.5 hours <CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 1 3.5 hours >CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 28 3.5 hours<CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 28 3.5 hours> CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 28 3.5 hours> CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 1 3.5 hours >CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Screening 3.5 hours <CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 1 3.5 hours <CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Screening 3.5 hours >CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 28 3.5 hours<CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Screening 3.5 hours >CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 1 3.5 hours <CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 1 3.5 hours >CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 28 3.5 hours> CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 28 3.5 hours<CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Screening 3.5 hours <CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 28 3.5 hours<CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 28 3.5 hours> CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Screening 3.5 hours >CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 1 3.5 hours >CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Screening 3.5 hours <CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for Heart Rate | Heart rate Day 1 3.5 hours <CCR | 0 Participants |
Secondary
Number of Participants Outside the Normal Range for SBP and DBP
Blood pressure measurements were taken at pre-dose and at 120 min (completion of meal) on Day 1 and Day 28. The clinical concern range (CCR) for SBP was greater than (\<) 85 and less than (\>) 160 and for DBP the range was \<45 and \>100. Data for semi-supine position has been presented. Baseline was Screening2/Baseline values.
Time frame: Screening2/Baseline (Day -30 to -1), Day 1 and 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 1 3.5 hours - 2 | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 28 3.5 hours - 2 | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | DBP Screening 3.5 hours>CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | SBP Screening 3.5 hours < CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 1 3.5 hours | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 1 3.5 hours< CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 1 3.5 hours>CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | SBP Screening 3.5 hours>CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 28 3.5 hours | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 28 3.5 hours< CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 28 3.5 hours>CCR | 0 Participants |
| Placebo | Number of Participants Outside the Normal Range for SBP and DBP | DBP Screening 3.5 hours< CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Screening 3.5 hours>CCR | 1 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Screening 3.5 hours< CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 1 3.5 hours>CCR | 1 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 1 3.5 hours | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 1 3.5 hours - 2 | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Screening 3.5 hours>CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Screening 3.5 hours < CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 28 3.5 hours>CCR | 1 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 28 3.5 hours< CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 1 3.5 hours< CCR | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 28 3.5 hours - 2 | 0 Participants |
| GSK962040 10 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 28 3.5 hours | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Screening 3.5 hours>CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Screening 3.5 hours < CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Screening 3.5 hours>CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 1 3.5 hours< CCR | 1 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 1 3.5 hours>CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 28 3.5 hours< CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 28 3.5 hours>CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Screening 3.5 hours< CCR | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 1 3.5 hours | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 1 3.5 hours - 2 | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 28 3.5 hours | 0 Participants |
| GSK962040 50 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 28 3.5 hours - 2 | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 28 3.5 hours>CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 28 3.5 hours< CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Screening 3.5 hours < CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 1 3.5 hours - 2 | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 1 3.5 hours>CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Day 1 3.5 hours< CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 28 3.5 hours - 2 | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 28 3.5 hours | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Screening 3.5 hours>CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Screening 3.5 hours< CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | SBP Screening 3.5 hours>CCR | 0 Participants |
| GSK962040 125 mg | Number of Participants Outside the Normal Range for SBP and DBP | DBP Day 1 3.5 hours | 0 Participants |
Secondary
Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs)
An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. Data for on-treatment adverse events is reported.
Time frame: Up to follow-up (5-10 days post last dose)
Population: All Subjects population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Any on-treatment AEs | 13 Participants |
| Placebo | Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Any on-treatment SAEs | 1 Participants |
| GSK962040 10 mg | Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Any on-treatment SAEs | 0 Participants |
| GSK962040 10 mg | Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Any on-treatment AEs | 14 Participants |
| GSK962040 50 mg | Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Any on-treatment AEs | 13 Participants |
| GSK962040 50 mg | Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Any on-treatment SAEs | 1 Participants |
| GSK962040 125 mg | Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Any on-treatment AEs | 18 Participants |
| GSK962040 125 mg | Number of Participants With On-treatment Adverse Events (AES) and Serious Adverse Events(SAEs) | Any on-treatment SAEs | 0 Participants |
Secondary
Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points
Analysis of pre-dose (trough) concentration at the end of the dosing interval (Ct) was planned to be performed from the samples collected at Pre -dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28.
Time frame: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Population: PK population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points | Day 14 | 63.73 Liters | Standard Deviation 34.853 |
| Placebo | Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points | Day 28 | 62.60 Liters | Standard Deviation 32.83 |
| GSK962040 10 mg | Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points | Day 14 | 214.26 Liters | Standard Deviation 146.572 |
| GSK962040 10 mg | Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points | Day 28 | 205.03 Liters | Standard Deviation 84.251 |
| GSK962040 50 mg | Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points | Day 14 | 537.23 Liters | Standard Deviation 290.37 |
| GSK962040 50 mg | Pre-dose (Trough) Concentration at the End of the Dosing Interval (Ct) at Specified Time Points | Day 28 | 597.39 Liters | Standard Deviation 321.225 |
Secondary
Time of Occurrence of Cmax (Tmax) at Specified Time Points
Tmax is defined as the time to reach the observed maximum concentration. Samples were collected at the following times: Tmax was determined directly from the raw concentration-time data. Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose.
Time frame: Pre-dose and 1.5, 2.5, 3.5, 4.5, and 5.5 hours post dose on Day 1 and 28
Population: PK population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time of Occurrence of Cmax (Tmax) at Specified Time Points | Day 1 | 2.174 Hour | Standard Deviation 0.9066 |
| Placebo | Time of Occurrence of Cmax (Tmax) at Specified Time Points | Day 28 | 2.189 Hour | Standard Deviation 1.3976 |
| GSK962040 10 mg | Time of Occurrence of Cmax (Tmax) at Specified Time Points | Day 1 | 2.238 Hour | Standard Deviation 1.0697 |
| GSK962040 10 mg | Time of Occurrence of Cmax (Tmax) at Specified Time Points | Day 28 | 2.168 Hour | Standard Deviation 0.7224 |
| GSK962040 50 mg | Time of Occurrence of Cmax (Tmax) at Specified Time Points | Day 1 | 2.092 Hour | Standard Deviation 0.8419 |
| GSK962040 50 mg | Time of Occurrence of Cmax (Tmax) at Specified Time Points | Day 28 | 2.026 Hour | Standard Deviation 1.2038 |
Secondary
Time to First Bowel Movement After First Dose
The time to first bowel movement was calculated as the time of the first bowel movement after the first dose in hours (floored) for each participant. If a participant had fewer than 5 days worth of data then the daily mean for that week was set to missing for the following two parameters: Bowel Movement Count and Stool Consistency. Seventeen participants who entered their time of first instance of bowel movement before taking first dose were excluded from the summary statistics of time to first bowel movement.
Time frame: Up to Day 28
Population: All Subjects Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time to First Bowel Movement After First Dose | 28.94 hours | Standard Deviation 25.044 |
| GSK962040 10 mg | Time to First Bowel Movement After First Dose | 53.98 hours | Standard Deviation 67.901 |
| GSK962040 50 mg | Time to First Bowel Movement After First Dose | 17.52 hours | Standard Deviation 19.286 |
| GSK962040 125 mg | Time to First Bowel Movement After First Dose | 15.73 hours | Standard Deviation 15.648 |