Autoimmune Diseases
Conditions
Keywords
Sentinel-dosing, GSK2982772, Japnese, Dose-ascending, Crossover, Healthy
Brief summary
The study plans to enroll approximately 12 subjects. The main objective of the study is to assess the safety, tolerability and pharmacokinetics (PK) of the three times a day (TID), dosing of GSK2982772, in Japanese healthy male subjects. The study will comprise of four study periods each at least 7 days in duration with subjects in-house for 4 nights (through 72 hrs after the first dose). During each treatment period (TP), subjects will be admitted to the unit the day before dosing and will be discharged after completion of the 72 hours post-dose assessments. There will be a washout of atleast 7-days between the TP doses for each individual, post which there will be 7-days follow-up. The dose range proposed in this study is based on a low starting dose, which will be escalated to the highest dose that is intended for the Phase 2b dose range study. The decision to proceed to the next dose-level, of GSK2982772 within the study will be made by principal investigator and GSK Medical Monitor per each dosing periods. The study duration is approximately 22 weeks.
Interventions
DRUGGSK2982772
GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route
DRUGPlacebo
Placebo matching GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
It is a double-blinded study, where the subjects, investigators and the site-staff will be blinded.
Intervention model description
Study will comprise of four TPs, each of at least 7 days in duration with subjects in-house for 4 nights (through 72 hours after the first dose). During each TP, subjects will be admitted to the unit, day before dosing and will be discharged after completion of 72 hours post-dose assessments. dose will be administered TID, in an ascending manner. Every individual subject will receive placebo and GSK2982772 (60, 120,240 mg TID) as per assigned sequence. For TID dosing, GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hour (the second dosing) and 14 hour (the third dosing) on Day 1 in each period. On Day 1, subjects will fast 8hour overnight prior to first dose. breakfast will be served approximately 2hour after first dose. Lunch and dinner will be served between 2 to 3hour prior to second and third doses, respectively. A washout of atleast 7-days between the TP doses for each individual subject.
Eligibility
Sex/Gender
MALE
Age
20 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must be 20 to 64 years of age inclusive, at the time of signing the informed consent. * Healthy as determined by the Investigators based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests, and ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the Investigators in consultation with the GSK Medical Monitor agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * Body weight \>= 50 kilogram (kg) and body mass index (BMI) within the range 18.5-24.9 kg/meter square (inclusive). * Japanese male subjects must agree to use contraception as detailed in protocol during the treatment period and until follow up visit. * Capable of giving informed consent as described in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Abnormal Neurological Examinations of TID Doses for One Day of GSK2982772 | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period | Neurological examinations including: mental status, gait, balance, coordination, cranial nerves, motor power, reflexes, and sensory system (light touch and pain) were assessed in participants specified time points. |
| Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Up to 24 hours at each Treatment Period | Continuous cardiac telemetry was performed and number of participants with abnormal clinically significant and not clinically significant values are presented. |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each treatment period | Blood pressure of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period | Pulse rate of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period | Temperature of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | From the day of first dose to 39 days | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety population comprised of all participants who have received at least one dose of study treatment. This population was used for the safety analyses. |
| Change From Baseline in Clinical Chemistry Parameters | Baseline (Day -1) and at 72 hours at each treatment period | Blood samples were collected for the analysis of clinical chemistry parameters including: glucose, calcium, cholesterol, chloride, high density lipoprotein (HDL) cholesterol, potassium, low density lipoprotein (LDL) cholesterol, phosphate, sodium, triglycerides and urea. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of clinical chemistry parameters including: albumin and protein. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of clinical chemistry parameters including: ALP, ALT, AST, CK, GGT and LDH. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Clinical Chemistry Parameter: Amylase | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of clinical chemistry parameter: amylase. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of clinical chemistry parameters:direct bilirubin, bilirubin, creatinine and urate. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Clinical Chemistry Parameter: C-reactive Protein (CRP) of TID Doses for One Day of GSK2982772 | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of clinical chemistry parameter: CRP. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Hematology Parameter: Hematocrit | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Hematology Parameter: Hemoglobin | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin (MCH) | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of hematology parameter: erythrocyte MCH. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV) | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of hematology parameter: erythrocyte MCV. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Hematology Parameter: Erythrocytes | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of hematology parameter: erythrocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of hematology parameter: percentage reticulocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of hematology parameters including platelet count and leukocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Baseline (Day -1) and at 72 hours at each Treatment Period | Blood samples were collected for the analysis of hematology parameters including neutrophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, eosinophils/leukocytes and basophils/leukocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Urine Potential of Hydrogen (pH) | Baseline (Day -1) and at 72 hours at each Treatment Period | Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in Urine Specific Gravity | Baseline (Day -1) and at 72 hours at each Treatment Period | Urine samples were collected for analysis of urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. The urinary specific gravity measurement is a routine part of urinalysis. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Number of Participants With Abnormal Urinalysis Results by Dipstick Method | At 72 hours of each Treatment Period | Urine samples were collected to assess urine bilirubin, urine glucose, urine ketones, urine occult blood, urine protein and urine urobilinogen by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine bilirubin, urine occult blood, urine glucose, urine ketones, urine protein and urine urobilinogen can be read as negative (-) and trace (+-) indicating proportional concentrations in the urine sample. |
| Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period | Full 12-lead ECGs were recorded in participant using an automated ECG machine. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
| Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period | Full 12-lead ECGs were recorded in participants using an automated ECG machine and measured PR, QRS, QT and QTcF intervals. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment Period | Blood samples were collected from participants at indicated time points and analyzed for Cmax and observed trough drug plasma concentrations: C0, C7, C14 and C24 after the administration of TID doses of GSK2982772. |
| Terminal Half Life (t1/2) After the Third TID Dose for One Day of GSK2982772 | Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment Period | Blood samples were collected from participants at indicated time points and t1/2 was analyzed after the administration of third TID dose of GSK2982772. |
| Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment Period | Blood samples were collected from participants at indicated time points and Tmax was analyzed after the administration of TID doses of GSK2982772. |
| Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | Pre-dose, 20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours, 7 hours 20 minutes, 7 hours 40 minutes, 8, 8.5, 9, 10, 12, 14 hours, 14 hours 20 minutes, 14 hours 40 minutes, 15, 15.5, 16, 17, 19, 22 and 24 hours post-dose at each Treatment Period | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24) and AUC over each dose: AUC(0-7), AUC (7-14) and AUC (14-24) after the administration of TID doses of GSK2982772. Pharmacokinetic analysis was conducted using standard non-compartmental methods. All participants in the safety population for whom a pharmacokinetic sample has been obtained and analyzed was included in the pharmacokinetic population. |
Countries
Japan
Participant flow
Recruitment details
This was a 4-way crossover, single-center, randomized, double-blind, dose-ascending, placebo (PBO)-controlled study to evaluate the safety, tolerability, and pharmacokinetics of oral TID doses (thrice a day) of GSK2982772 in healthy male Japanese participants
Pre-assignment details
A total of 13 healthy male Japanese participants were enrolled in the study to receive GSK2982772 and PBO from a single center in Japan
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All study participants received GSK2982772 and PBO in four treatment sequences (A,B,C &D) at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 2, 4 Days | Physician Decision | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 26.2 Years STANDARD_DEVIATION 7.34 |
| Race/Ethnicity, Customized Asian-Japanese/East Asian/South East AsianHeritage | 13 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 13 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 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 0 / 12 | 1 / 12 | 0 / 12 | 0 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772
Temperature of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 2 hours | 0.22 Degrees Celsius | Standard Deviation 0.204 |
| Placebo | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 7 hours | 0.47 Degrees Celsius | Standard Deviation 0.274 |
| Placebo | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 14 hours | 0.39 Degrees Celsius | Standard Deviation 0.264 |
| Placebo | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 24 hours | 0.07 Degrees Celsius | Standard Deviation 0.223 |
| Placebo | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 48 hours | 0.06 Degrees Celsius | Standard Deviation 0.297 |
| Placebo | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 72 hours | 0.09 Degrees Celsius | Standard Deviation 0.257 |
| GSK2982772 60 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 72 hours | 0.00 Degrees Celsius | Standard Deviation 0.191 |
| GSK2982772 60 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 24 hours | -0.05 Degrees Celsius | Standard Deviation 0.239 |
| GSK2982772 60 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 2 hours | 0.32 Degrees Celsius | Standard Deviation 0.199 |
| GSK2982772 60 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 14 hours | 0.48 Degrees Celsius | Standard Deviation 0.191 |
| GSK2982772 60 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 7 hours | 0.51 Degrees Celsius | Standard Deviation 0.231 |
| GSK2982772 60 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 48 hours | -0.07 Degrees Celsius | Standard Deviation 0.235 |
| GSK2982772 120 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 7 hours | 0.43 Degrees Celsius | Standard Deviation 0.261 |
| GSK2982772 120 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 14 hours | 0.40 Degrees Celsius | Standard Deviation 0.388 |
| GSK2982772 120 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 24 hours | 0.08 Degrees Celsius | Standard Deviation 0.237 |
| GSK2982772 120 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 72 hours | 0.09 Degrees Celsius | Standard Deviation 0.284 |
| GSK2982772 120 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 48 hours | -0.08 Degrees Celsius | Standard Deviation 0.222 |
| GSK2982772 120 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 2 hours | 0.12 Degrees Celsius | Standard Deviation 0.241 |
| GSK2982772 240 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 48 hours | 0.12 Degrees Celsius | Standard Deviation 0.292 |
| GSK2982772 240 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 72 hours | 0.24 Degrees Celsius | Standard Deviation 0.271 |
| GSK2982772 240 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 7 hours | 0.48 Degrees Celsius | Standard Deviation 0.366 |
| GSK2982772 240 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 24 hours | 0.08 Degrees Celsius | Standard Deviation 0.286 |
| GSK2982772 240 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 2 hours | 0.18 Degrees Celsius | Standard Deviation 0.276 |
| GSK2982772 240 mg | Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772 | 14 hours | 0.65 Degrees Celsius | Standard Deviation 0.258 |
Primary
Change From Baseline in Clinical Chemistry Parameter: Amylase
Blood samples were collected for the analysis of clinical chemistry parameter: amylase. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameter: Amylase | 4.2 Units per liter | Standard Deviation 10.56 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameter: Amylase | 9.1 Units per liter | Standard Deviation 6.26 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameter: Amylase | 4.4 Units per liter | Standard Deviation 9.34 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameter: Amylase | 1.1 Units per liter | Standard Deviation 8.4 |
Primary
Change From Baseline in Clinical Chemistry Parameter: C-reactive Protein (CRP) of TID Doses for One Day of GSK2982772
Blood samples were collected for the analysis of clinical chemistry parameter: CRP. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameter: C-reactive Protein (CRP) of TID Doses for One Day of GSK2982772 | -0.078 Milligrams per liter | Standard Deviation 0.229 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameter: C-reactive Protein (CRP) of TID Doses for One Day of GSK2982772 | -0.016 Milligrams per liter | Standard Deviation 0.0268 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameter: C-reactive Protein (CRP) of TID Doses for One Day of GSK2982772 | -0.050 Milligrams per liter | Standard Deviation 0.1028 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameter: C-reactive Protein (CRP) of TID Doses for One Day of GSK2982772 | 0.126 Milligrams per liter | Standard Deviation 0.539 |
Primary
Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for the analysis of clinical chemistry parameters including: glucose, calcium, cholesterol, chloride, high density lipoprotein (HDL) cholesterol, potassium, low density lipoprotein (LDL) cholesterol, phosphate, sodium, triglycerides and urea. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each treatment period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Glucose | -0.240543 Millimoles per liter | Standard Deviation 0.1426732 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Chloride | 1.1 Millimoles per liter | Standard Deviation 1.38 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Phosphate | 0.064580 Millimoles per liter | Standard Deviation 0.0963795 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Calcium | 0.016633 Millimoles per liter | Standard Deviation 0.0683974 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | LDL Cholesterol | 0.036635 Millimoles per liter | Standard Deviation 0.1670318 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | HDL Cholesterol | -0.071115 Millimoles per liter | Standard Deviation 0.1097839 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Cholesterol | 0.000000 Millimoles per liter | Standard Deviation 0.2092177 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Urea | -0.09223 Millimoles per liter | Standard Deviation 0.656241 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Triglycerides | 0.19398 Millimoles per liter | Standard Deviation 0.117614 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Potassium | -0.06 Millimoles per liter | Standard Deviation 0.156 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters | Sodium | 1.5 Millimoles per liter | Standard Deviation 1.78 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Potassium | 0.01 Millimoles per liter | Standard Deviation 0.329 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Sodium | 1.3 Millimoles per liter | Standard Deviation 1.72 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | LDL Cholesterol | 0.101285 Millimoles per liter | Standard Deviation 0.1673953 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Phosphate | 0.053817 Millimoles per liter | Standard Deviation 0.1210793 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Cholesterol | 0.073270 Millimoles per liter | Standard Deviation 0.2657498 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Urea | -0.21123 Millimoles per liter | Standard Deviation 0.796454 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Chloride | 0.2 Millimoles per liter | Standard Deviation 2.25 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Triglycerides | 0.12618 Millimoles per liter | Standard Deviation 0.153495 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | HDL Cholesterol | -0.034480 Millimoles per liter | Standard Deviation 0.1070976 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Calcium | 0.058217 Millimoles per liter | Standard Deviation 0.0341987 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters | Glucose | -0.282176 Millimoles per liter | Standard Deviation 0.2348638 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Triglycerides | 0.13372 Millimoles per liter | Standard Deviation 0.286674 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Glucose | -0.240543 Millimoles per liter | Standard Deviation 0.2902134 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Calcium | -0.022871 Millimoles per liter | Standard Deviation 0.0732901 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Cholesterol | 0.015085 Millimoles per liter | Standard Deviation 0.3458001 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Chloride | 1.2 Millimoles per liter | Standard Deviation 1.59 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | HDL Cholesterol | -0.084045 Millimoles per liter | Standard Deviation 0.1046815 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Potassium | 0.03 Millimoles per liter | Standard Deviation 0.501 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | LDL Cholesterol | 0.017240 Millimoles per liter | Standard Deviation 0.2663211 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Phosphate | 0.002691 Millimoles per liter | Standard Deviation 0.1155721 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Sodium | 0.9 Millimoles per liter | Standard Deviation 1.93 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters | Urea | -0.03273 Millimoles per liter | Standard Deviation 0.30953 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Potassium | -0.07 Millimoles per liter | Standard Deviation 0.419 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Urea | -0.31238 Millimoles per liter | Standard Deviation 0.70586 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Sodium | 1.4 Millimoles per liter | Standard Deviation 1.83 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | HDL Cholesterol | -0.116370 Millimoles per liter | Standard Deviation 0.0578247 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Chloride | 0.6 Millimoles per liter | Standard Deviation 1.68 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Cholesterol | -0.049565 Millimoles per liter | Standard Deviation 0.3560217 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Triglycerides | 0.13466 Millimoles per liter | Standard Deviation 0.368074 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Calcium | -0.004158 Millimoles per liter | Standard Deviation 0.1036024 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Glucose | -0.226666 Millimoles per liter | Standard Deviation 0.2554319 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | Phosphate | 0.018836 Millimoles per liter | Standard Deviation 0.1366196 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters | LDL Cholesterol | -0.043100 Millimoles per liter | Standard Deviation 0.192679 |
Primary
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Blood samples were collected for the analysis of clinical chemistry parameters including: albumin and protein. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -1.4 Grams per liter | Standard Deviation 2.64 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -1.3 Grams per liter | Standard Deviation 3.96 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | 0.8 Grams per liter | Standard Deviation 2.12 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -0.4 Grams per liter | Standard Deviation 1.62 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -1.6 Grams per liter | Standard Deviation 2.47 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -2.1 Grams per liter | Standard Deviation 3.7 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Albumin | -2.5 Grams per liter | Standard Deviation 3.23 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein | Protein | -2.3 Grams per liter | Standard Deviation 4.27 |
Primary
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH)
Blood samples were collected for the analysis of clinical chemistry parameters including: ALP, ALT, AST, CK, GGT and LDH. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | ALP | -9.1 International units per liter | Standard Deviation 17.32 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | ALT | -0.5 International units per liter | Standard Deviation 3.66 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | AST | -0.6 International units per liter | Standard Deviation 2.68 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | CK | -19.1 International units per liter | Standard Deviation 14.95 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | GGT | -0.5 International units per liter | Standard Deviation 0.67 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | LDH | -17.7 International units per liter | Standard Deviation 9.76 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | LDH | -11.3 International units per liter | Standard Deviation 8.01 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | CK | -34.2 International units per liter | Standard Deviation 21.7 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | ALP | -6.8 International units per liter | Standard Deviation 12.63 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | AST | 0.3 International units per liter | Standard Deviation 1.76 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | ALT | 0.5 International units per liter | Standard Deviation 2.47 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | GGT | -0.5 International units per liter | Standard Deviation 1.62 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | ALT | -2.2 International units per liter | Standard Deviation 3.33 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | AST | -1.8 International units per liter | Standard Deviation 3.28 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | CK | -51.7 International units per liter | Standard Deviation 48.61 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | LDH | -21.6 International units per liter | Standard Deviation 14.92 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | GGT | -1.8 International units per liter | Standard Deviation 2.93 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | ALP | -10.6 International units per liter | Standard Deviation 14.41 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | GGT | -1.5 International units per liter | Standard Deviation 2.32 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | LDH | -21.3 International units per liter | Standard Deviation 10.34 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | ALT | -1.3 International units per liter | Standard Deviation 4.59 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | CK | -39.6 International units per liter | Standard Deviation 32.91 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | ALP | -9.0 International units per liter | Standard Deviation 14.65 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH) | AST | -2.5 International units per liter | Standard Deviation 6.64 |
Primary
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid)
Blood samples were collected for the analysis of clinical chemistry parameters:direct bilirubin, bilirubin, creatinine and urate. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Direct bilirubin | 0.428 Micromoles per liter | Standard Deviation 1.0629 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Bilirubin | 2.850 Micromoles per liter | Standard Deviation 4.7998 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Creatinine | 0.8840 Micromoles per liter | Standard Deviation 7.47252 |
| Placebo | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Urate | 21.8093 Micromoles per liter | Standard Deviation 29.82999 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Bilirubin | 2.850 Micromoles per liter | Standard Deviation 4.7998 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Creatinine | 0.5157 Micromoles per liter | Standard Deviation 4.4673 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Urate | 9.4177 Micromoles per liter | Standard Deviation 23.16992 |
| GSK2982772 60 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Direct bilirubin | 0.285 Micromoles per liter | Standard Deviation 0.9873 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Creatinine | 0.6630 Micromoles per liter | Standard Deviation 5.25184 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Bilirubin | 1.568 Micromoles per liter | Standard Deviation 5.9441 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Urate | 17.8440 Micromoles per liter | Standard Deviation 17.93389 |
| GSK2982772 120 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Direct bilirubin | 0.143 Micromoles per liter | Standard Deviation 1.1432 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Urate | 8.4263 Micromoles per liter | Standard Deviation 27.95138 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Bilirubin | -0.428 Micromoles per liter | Standard Deviation 4.0679 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Direct bilirubin | -0.285 Micromoles per liter | Standard Deviation 0.9873 |
| GSK2982772 240 mg | Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid) | Creatinine | 1.6943 Micromoles per liter | Standard Deviation 3.97949 |
Primary
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
Full 12-lead ECGs were recorded in participants using an automated ECG machine and measured PR, QRS, QT and QTcF intervals. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 14 hours | -7.5 Milliseconds | Standard Deviation 9.95 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 7 hours | -22.7 Milliseconds | Standard Deviation 18.79 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 2 hours | -8.0 Milliseconds | Standard Deviation 13.56 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 7 hours | 0.7 Milliseconds | Standard Deviation 6.95 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 72 hours | -2.9 Milliseconds | Standard Deviation 12.92 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 72 hours | 1.0 Milliseconds | Standard Deviation 4.47 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 48 hours | 1.0 Milliseconds | Standard Deviation 6.12 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 14 hours | 3.5 Milliseconds | Standard Deviation 8.4 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 14 hours | -3.6 Milliseconds | Standard Deviation 16.5 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 24 hours | 1.3 Milliseconds | Standard Deviation 5.14 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 7 hours | 2.1 Milliseconds | Standard Deviation 15.02 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 24 hours | 1.2 Milliseconds | Standard Deviation 7.26 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 7 hours | -9.5 Milliseconds | Standard Deviation 13.7 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 2 hours | -0.1 Milliseconds | Standard Deviation 16.4 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 72 hours | -18.0 Milliseconds | Standard Deviation 17.2 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 48 hours | 2.0 Milliseconds | Standard Deviation 13.75 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 48 hours | -1.9 Milliseconds | Standard Deviation 13.55 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 48 hours | -3.3 Milliseconds | Standard Deviation 9.55 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 2 hours | -3.7 Milliseconds | Standard Deviation 8.22 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 72 hours | -0.2 Milliseconds | Standard Deviation 15.92 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 24 hours | -0.5 Milliseconds | Standard Deviation 14.44 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 24 hours | -8.3 Milliseconds | Standard Deviation 13.59 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 14 hours | -20.5 Milliseconds | Standard Deviation 17.35 |
| Placebo | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 2 hours | -2.3 Milliseconds | Standard Deviation 6.6 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 24 hours | 0.7 Milliseconds | Standard Deviation 14.95 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 2 hours | -2.3 Milliseconds | Standard Deviation 7.62 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 7 hours | -8.3 Milliseconds | Standard Deviation 7.95 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 14 hours | -0.8 Milliseconds | Standard Deviation 11.92 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 24 hours | -0.2 Milliseconds | Standard Deviation 8.07 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 48 hours | 1.0 Milliseconds | Standard Deviation 9.89 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 72 hours | 1.2 Milliseconds | Standard Deviation 8.2 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 2 hours | -2.7 Milliseconds | Standard Deviation 7.69 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 7 hours | -0.5 Milliseconds | Standard Deviation 4.52 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 14 hours | 0.8 Milliseconds | Standard Deviation 1.59 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 24 hours | 0.7 Milliseconds | Standard Deviation 3.34 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 48 hours | -1.3 Milliseconds | Standard Deviation 5.28 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 72 hours | 0.2 Milliseconds | Standard Deviation 5.62 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 2 hours | -3.2 Milliseconds | Standard Deviation 22.94 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 7 hours | -29.7 Milliseconds | Standard Deviation 15.06 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 14 hours | -21.3 Milliseconds | Standard Deviation 17.55 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 48 hours | -7.3 Milliseconds | Standard Deviation 10.39 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 72 hours | -11.8 Milliseconds | Standard Deviation 13.42 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 2 hours | 4.0 Milliseconds | Standard Deviation 19.41 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 7 hours | -6.7 Milliseconds | Standard Deviation 15.07 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 14 hours | -3.8 Milliseconds | Standard Deviation 12.75 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 24 hours | 7.8 Milliseconds | Standard Deviation 15.82 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 48 hours | 1.9 Milliseconds | Standard Deviation 7.18 |
| GSK2982772 60 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 72 hours | 2.6 Milliseconds | Standard Deviation 11.37 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 2 hours | -2.2 Milliseconds | Standard Deviation 7.16 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 2 hours | -7.1 Milliseconds | Standard Deviation 18.6 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 24 hours | -13.5 Milliseconds | Standard Deviation 16.65 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 2 hours | -9.8 Milliseconds | Standard Deviation 20.69 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 48 hours | 2.8 Milliseconds | Standard Deviation 11.98 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 7 hours | -1.4 Milliseconds | Standard Deviation 16.59 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 24 hours | -7.8 Milliseconds | Standard Deviation 19.6 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 14 hours | -0.2 Milliseconds | Standard Deviation 10.77 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 2 hours | 0.5 Milliseconds | Standard Deviation 8.36 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 14 hours | -1.4 Milliseconds | Standard Deviation 13.94 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 7 hours | -3.8 Milliseconds | Standard Deviation 11.77 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 14 hours | 0.3 Milliseconds | Standard Deviation 5.52 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 48 hours | -15.2 Milliseconds | Standard Deviation 20.85 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 24 hours | -1.3 Milliseconds | Standard Deviation 7.74 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 14 hours | -20.0 Milliseconds | Standard Deviation 20.47 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 7 hours | -22.2 Milliseconds | Standard Deviation 22.33 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 48 hours | -11.3 Milliseconds | Standard Deviation 12.2 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 48 hours | -0.2 Milliseconds | Standard Deviation 10.5 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 72 hours | -14.7 Milliseconds | Standard Deviation 20.44 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 7 hours | -0.5 Milliseconds | Standard Deviation 6.39 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 72 hours | -4.8 Milliseconds | Standard Deviation 13.3 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 72 hours | 1.0 Milliseconds | Standard Deviation 8.33 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 72 hours | 2.0 Milliseconds | Standard Deviation 13.43 |
| GSK2982772 120 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 24 hours | 1.7 Milliseconds | Standard Deviation 9.18 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 7 hours | -7.2 Milliseconds | Standard Deviation 14.83 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 2 hours | -4.7 Milliseconds | Standard Deviation 17.53 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 24 hours | -1.8 Milliseconds | Standard Deviation 9.04 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 7 hours | -31.3 Milliseconds | Standard Deviation 24.1 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 72 hours | 4.8 Milliseconds | Standard Deviation 13.47 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 14 hours | -23.5 Milliseconds | Standard Deviation 20.91 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 48 hours | 3.7 Milliseconds | Standard Deviation 7.33 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 24 hours | -6.7 Milliseconds | Standard Deviation 13.84 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 72 hours | -4.5 Milliseconds | Standard Deviation 12.26 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 48 hours | -15.7 Milliseconds | Standard Deviation 17.24 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 24 hours | 1.5 Milliseconds | Standard Deviation 13.32 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QT interval, 72 hours | -23.3 Milliseconds | Standard Deviation 12.69 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 48 hours | -10.0 Milliseconds | Standard Deviation 16.31 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 2 hours | 0.6 Milliseconds | Standard Deviation 17.64 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 14 hours | -4.2 Milliseconds | Standard Deviation 11 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 2 hours | -4.0 Milliseconds | Standard Deviation 7.48 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 14 hours | 1.5 Milliseconds | Standard Deviation 7.34 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QTcF interval, 14 hours | -4.8 Milliseconds | Standard Deviation 15.6 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 24 hours | 0.7 Milliseconds | Standard Deviation 5.99 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 7 hours | 1.7 Milliseconds | Standard Deviation 4.33 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | PR interval, 7 hours | -7.0 Milliseconds | Standard Deviation 10.04 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 48 hours | -2.5 Milliseconds | Standard Deviation 5.13 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 72 hours | 0.3 Milliseconds | Standard Deviation 4.96 |
| GSK2982772 240 mg | Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772 | QRS duration, 2 hours | 0.3 Milliseconds | Standard Deviation 4.89 |
Primary
Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate
Full 12-lead ECGs were recorded in participant using an automated ECG machine. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 2 hours | 3.1 Beats per minute | Standard Deviation 5.2 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 7 hours | 10.7 Beats per minute | Standard Deviation 5.21 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 14 hours | 6.9 Beats per minute | Standard Deviation 3.18 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 24 hours | 3.0 Beats per minute | Standard Deviation 4.31 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 48 hours | 0.6 Beats per minute | Standard Deviation 3.99 |
| Placebo | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 72 hours | 6.2 Beats per minute | Standard Deviation 5.57 |
| GSK2982772 60 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 72 hours | 5.9 Beats per minute | Standard Deviation 3.2 |
| GSK2982772 60 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 24 hours | 2.3 Beats per minute | Standard Deviation 4.03 |
| GSK2982772 60 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 2 hours | 2.9 Beats per minute | Standard Deviation 4.54 |
| GSK2982772 60 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 14 hours | 7.3 Beats per minute | Standard Deviation 4.2 |
| GSK2982772 60 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 7 hours | 9.6 Beats per minute | Standard Deviation 4.72 |
| GSK2982772 60 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 48 hours | 3.7 Beats per minute | Standard Deviation 3.31 |
| GSK2982772 120 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 7 hours | 9.0 Beats per minute | Standard Deviation 5.53 |
| GSK2982772 120 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 14 hours | 7.7 Beats per minute | Standard Deviation 5.35 |
| GSK2982772 120 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 24 hours | 2.1 Beats per minute | Standard Deviation 6.79 |
| GSK2982772 120 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 72 hours | 3.7 Beats per minute | Standard Deviation 6.05 |
| GSK2982772 120 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 48 hours | 1.3 Beats per minute | Standard Deviation 6.96 |
| GSK2982772 120 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 2 hours | 0.6 Beats per minute | Standard Deviation 3.78 |
| GSK2982772 240 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 48 hours | 2.3 Beats per minute | Standard Deviation 7.62 |
| GSK2982772 240 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 72 hours | 8.3 Beats per minute | Standard Deviation 5.87 |
| GSK2982772 240 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 7 hours | 10.8 Beats per minute | Standard Deviation 7.79 |
| GSK2982772 240 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 24 hours | 1.8 Beats per minute | Standard Deviation 4.82 |
| GSK2982772 240 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 2 hours | 2.0 Beats per minute | Standard Deviation 5.86 |
| GSK2982772 240 mg | Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate | 14 hours | 8.3 Beats per minute | Standard Deviation 4.18 |
Primary
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin (MCH)
Blood samples were collected for the analysis of hematology parameter: erythrocyte MCH. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin (MCH) | 0.12 Picograms | Standard Deviation 0.269 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin (MCH) | 0.17 Picograms | Standard Deviation 0.299 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin (MCH) | 0.10 Picograms | Standard Deviation 0.234 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin (MCH) | 0.15 Picograms | Standard Deviation 0.261 |
Primary
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV)
Blood samples were collected for the analysis of hematology parameter: erythrocyte MCV. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV) | -0.4 Femtoliters | Standard Deviation 0.9 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV) | -0.7 Femtoliters | Standard Deviation 0.89 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV) | -0.2 Femtoliters | Standard Deviation 0.39 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV) | -0.4 Femtoliters | Standard Deviation 0.9 |
Primary
Change From Baseline in Hematology Parameter: Erythrocytes
Blood samples were collected for the analysis of hematology parameter: erythrocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter: Erythrocytes | 0.058 10^12 cells per liter | Standard Deviation 0.2387 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameter: Erythrocytes | 0.126 10^12 cells per liter | Standard Deviation 0.1583 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameter: Erythrocytes | -0.059 10^12 cells per liter | Standard Deviation 0.1624 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameter: Erythrocytes | -0.035 10^12 cells per liter | Standard Deviation 0.2731 |
Primary
Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter: Hematocrit | 0.0039 Percentage of red blood cells in blood | Standard Deviation 0.01946 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameter: Hematocrit | 0.0075 Percentage of red blood cells in blood | Standard Deviation 0.01332 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameter: Hematocrit | -0.0048 Percentage of red blood cells in blood | Standard Deviation 0.01434 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameter: Hematocrit | -0.0043 Percentage of red blood cells in blood | Standard Deviation 0.02172 |
Primary
Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter: Hemoglobin | 2.4 Grams per liter | Standard Deviation 6.01 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameter: Hemoglobin | 4.6 Grams per liter | Standard Deviation 5.74 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameter: Hemoglobin | -1.4 Grams per liter | Standard Deviation 5.57 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameter: Hemoglobin | -0.4 Grams per liter | Standard Deviation 8.65 |
Primary
Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes
Blood samples were collected for the analysis of hematology parameter: percentage reticulocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes | 0.0002 Ratio of Reticulocytes to Erythrocytes | Standard Deviation 0.00221 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes | 0.0001 Ratio of Reticulocytes to Erythrocytes | Standard Deviation 0.00188 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes | -0.0008 Ratio of Reticulocytes to Erythrocytes | Standard Deviation 0.00242 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes | -0.0003 Ratio of Reticulocytes to Erythrocytes | Standard Deviation 0.00201 |
Primary
Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772
Blood samples were collected for the analysis of hematology parameters including neutrophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, eosinophils/leukocytes and basophils/leukocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Eosinophils/Leukocytes | -0.18 Percentage of cells in leukocytes | Standard Deviation 0.666 |
| Placebo | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Monocytes/Leukocytes | -1.13 Percentage of cells in leukocytes | Standard Deviation 1.598 |
| Placebo | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Basophils/Leukocytes | -0.02 Percentage of cells in leukocytes | Standard Deviation 0.18 |
| Placebo | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Lymphocytes/Leukocytes | 1.29 Percentage of cells in leukocytes | Standard Deviation 4.206 |
| Placebo | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Neutrophils/Leukocytes | 0.04 Percentage of cells in leukocytes | Standard Deviation 4.656 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Lymphocytes/Leukocytes | 1.02 Percentage of cells in leukocytes | Standard Deviation 4.329 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Eosinophils/Leukocytes | -0.22 Percentage of cells in leukocytes | Standard Deviation 1.335 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Basophils/Leukocytes | -0.01 Percentage of cells in leukocytes | Standard Deviation 0.09 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Monocytes/Leukocytes | -0.24 Percentage of cells in leukocytes | Standard Deviation 1.019 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Neutrophils/Leukocytes | -0.55 Percentage of cells in leukocytes | Standard Deviation 4.356 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Lymphocytes/Leukocytes | 1.49 Percentage of cells in leukocytes | Standard Deviation 4.847 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Neutrophils/Leukocytes | -0.75 Percentage of cells in leukocytes | Standard Deviation 5.841 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Monocytes/Leukocytes | -0.01 Percentage of cells in leukocytes | Standard Deviation 1.176 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Eosinophils/Leukocytes | -0.66 Percentage of cells in leukocytes | Standard Deviation 1.377 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Basophils/Leukocytes | -0.08 Percentage of cells in leukocytes | Standard Deviation 0.129 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Eosinophils/Leukocytes | -0.27 Percentage of cells in leukocytes | Standard Deviation 0.537 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Monocytes/Leukocytes | -0.48 Percentage of cells in leukocytes | Standard Deviation 1.532 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Neutrophils/Leukocytes | -1.57 Percentage of cells in leukocytes | Standard Deviation 8.363 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Lymphocytes/Leukocytes | 2.29 Percentage of cells in leukocytes | Standard Deviation 8.349 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772 | Basophils/Leukocytes | 0.02 Percentage of cells in leukocytes | Standard Deviation 0.134 |
Primary
Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772
Blood samples were collected for the analysis of hematology parameters including platelet count and leukocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Platelets | -1.8 10^9 cells per liter | Standard Deviation 21.35 |
| Placebo | Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Leukocytes | -0.43 10^9 cells per liter | Standard Deviation 0.927 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Leukocytes | -0.05 10^9 cells per liter | Standard Deviation 0.992 |
| GSK2982772 60 mg | Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Platelets | 2.5 10^9 cells per liter | Standard Deviation 26.12 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Platelets | -12.8 10^9 cells per liter | Standard Deviation 23.03 |
| GSK2982772 120 mg | Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Leukocytes | -0.42 10^9 cells per liter | Standard Deviation 1.214 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Platelets | -6.4 10^9 cells per liter | Standard Deviation 18.59 |
| GSK2982772 240 mg | Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772 | Leukocytes | -0.62 10^9 cells per liter | Standard Deviation 0.86 |
Primary
Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772
Pulse rate of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 2 hours | 0.9 Beats per minute | Standard Deviation 5.35 |
| Placebo | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 7 hours | 6.9 Beats per minute | Standard Deviation 4.17 |
| Placebo | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 14 hours | 3.3 Beats per minute | Standard Deviation 3.5 |
| Placebo | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 24 hours | -0.9 Beats per minute | Standard Deviation 4.74 |
| Placebo | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 48 hours | -1.7 Beats per minute | Standard Deviation 3.98 |
| Placebo | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 72 hours | -0.4 Beats per minute | Standard Deviation 6.57 |
| GSK2982772 60 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 72 hours | 5.0 Beats per minute | Standard Deviation 3.79 |
| GSK2982772 60 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 24 hours | 1.0 Beats per minute | Standard Deviation 3.64 |
| GSK2982772 60 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 2 hours | 1.7 Beats per minute | Standard Deviation 4.19 |
| GSK2982772 60 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 14 hours | 5.3 Beats per minute | Standard Deviation 3.58 |
| GSK2982772 60 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 7 hours | 9.4 Beats per minute | Standard Deviation 5.6 |
| GSK2982772 60 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 48 hours | 1.5 Beats per minute | Standard Deviation 3.37 |
| GSK2982772 120 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 7 hours | 8.9 Beats per minute | Standard Deviation 5.92 |
| GSK2982772 120 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 14 hours | 5.5 Beats per minute | Standard Deviation 4.44 |
| GSK2982772 120 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 24 hours | 1.1 Beats per minute | Standard Deviation 2.75 |
| GSK2982772 120 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 72 hours | 2.2 Beats per minute | Standard Deviation 4.91 |
| GSK2982772 120 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 48 hours | 1.3 Beats per minute | Standard Deviation 4.97 |
| GSK2982772 120 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 2 hours | 0.4 Beats per minute | Standard Deviation 4.1 |
| GSK2982772 240 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 48 hours | 4.3 Beats per minute | Standard Deviation 5.45 |
| GSK2982772 240 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 72 hours | 6.0 Beats per minute | Standard Deviation 5.48 |
| GSK2982772 240 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 7 hours | 10.4 Beats per minute | Standard Deviation 6.75 |
| GSK2982772 240 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 24 hours | 3.3 Beats per minute | Standard Deviation 4.11 |
| GSK2982772 240 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 2 hours | 0.8 Beats per minute | Standard Deviation 3.81 |
| GSK2982772 240 mg | Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772 | 14 hours | 8.3 Beats per minute | Standard Deviation 4.5 |
Primary
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Blood pressure of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each treatment period
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 48 hours | 0.8 Millimeters of mercury | Standard Deviation 6.05 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 72 hours | 1.9 Millimeters of mercury | Standard Deviation 9.23 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 7 hours | -0.3 Millimeters of mercury | Standard Deviation 8.99 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 14 hours | -4.4 Millimeters of mercury | Standard Deviation 5.16 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hours | 0.3 Millimeters of mercury | Standard Deviation 4.7 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 14 hours | 3.3 Millimeters of mercury | Standard Deviation 5.76 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 2 hours | 1.3 Millimeters of mercury | Standard Deviation 6.85 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 2 hours | 0.2 Millimeters of mercury | Standard Deviation 5.13 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hours | -2.2 Millimeters of mercury | Standard Deviation 6.15 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 7 hours | -7.3 Millimeters of mercury | Standard Deviation 6.75 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 48 hours | -1.3 Millimeters of mercury | Standard Deviation 6.88 |
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 72 hours | -0.2 Millimeters of mercury | Standard Deviation 5.25 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 48 hours | -0.3 Millimeters of mercury | Standard Deviation 6.24 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 2 hours | 0.4 Millimeters of mercury | Standard Deviation 7.55 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hours | 0.1 Millimeters of mercury | Standard Deviation 5.55 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hours | 0.3 Millimeters of mercury | Standard Deviation 6.41 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 7 hours | 2.5 Millimeters of mercury | Standard Deviation 6.65 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 72 hours | 0.3 Millimeters of mercury | Standard Deviation 6.66 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 2 hours | -2.5 Millimeters of mercury | Standard Deviation 7.22 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 48 hours | 1.3 Millimeters of mercury | Standard Deviation 5.83 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 14 hours | 1.0 Millimeters of mercury | Standard Deviation 6.06 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 14 hours | -5.3 Millimeters of mercury | Standard Deviation 8.29 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 72 hours | 2.3 Millimeters of mercury | Standard Deviation 8.57 |
| GSK2982772 60 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 7 hours | -7.0 Millimeters of mercury | Standard Deviation 8.12 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 48 hours | 1.2 Millimeters of mercury | Standard Deviation 4.26 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 2 hours | -1.9 Millimeters of mercury | Standard Deviation 5.73 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 7 hours | -8.2 Millimeters of mercury | Standard Deviation 8.33 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 14 hours | -6.9 Millimeters of mercury | Standard Deviation 5.88 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hours | -4.0 Millimeters of mercury | Standard Deviation 5.24 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 48 hours | -0.3 Millimeters of mercury | Standard Deviation 4.69 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 72 hours | -0.1 Millimeters of mercury | Standard Deviation 7.18 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 2 hours | 2.4 Millimeters of mercury | Standard Deviation 4.1 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 7 hours | -0.7 Millimeters of mercury | Standard Deviation 8.15 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 14 hours | 9.0 Millimeters of mercury | Standard Deviation 11.24 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hours | 1.4 Millimeters of mercury | Standard Deviation 6.07 |
| GSK2982772 120 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 72 hours | 3.8 Millimeters of mercury | Standard Deviation 7.57 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 2 hours | 0.6 Millimeters of mercury | Standard Deviation 5.3 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 72 hours | 4.5 Millimeters of mercury | Standard Deviation 5.04 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 24 hours | 2.9 Millimeters of mercury | Standard Deviation 5.93 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 72 hours | 2.8 Millimeters of mercury | Standard Deviation 10.84 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 48 hours | 0.5 Millimeters of mercury | Standard Deviation 9.3 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 14 hours | -4.3 Millimeters of mercury | Standard Deviation 8.88 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 48 hours | -1.1 Millimeters of mercury | Standard Deviation 5.52 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 7 hours | -5.9 Millimeters of mercury | Standard Deviation 8.75 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 2 hours | -2.2 Millimeters of mercury | Standard Deviation 8.09 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | DBP, 24 hours | -2.4 Millimeters of mercury | Standard Deviation 10.21 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 14 hours | 5.6 Millimeters of mercury | Standard Deviation 11.12 |
| GSK2982772 240 mg | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | SBP, 7 hours | 1.3 Millimeters of mercury | Standard Deviation 6.09 |
Primary
Change From Baseline in Urine Potential of Hydrogen (pH)
Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Urine Potential of Hydrogen (pH) | 0.13 pH | Standard Deviation 0.569 |
| GSK2982772 60 mg | Change From Baseline in Urine Potential of Hydrogen (pH) | 0.42 pH | Standard Deviation 0.515 |
| GSK2982772 120 mg | Change From Baseline in Urine Potential of Hydrogen (pH) | 0.42 pH | Standard Deviation 0.515 |
| GSK2982772 240 mg | Change From Baseline in Urine Potential of Hydrogen (pH) | -0.17 pH | Standard Deviation 0.537 |
Primary
Change From Baseline in Urine Specific Gravity
Urine samples were collected for analysis of urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. The urinary specific gravity measurement is a routine part of urinalysis. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Time frame: Baseline (Day -1) and at 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Urine Specific Gravity | 0.0093 Ratio of urine density to water density | Standard Deviation 0.00702 |
| GSK2982772 60 mg | Change From Baseline in Urine Specific Gravity | 0.0042 Ratio of urine density to water density | Standard Deviation 0.0078 |
| GSK2982772 120 mg | Change From Baseline in Urine Specific Gravity | 0.0068 Ratio of urine density to water density | Standard Deviation 0.00631 |
| GSK2982772 240 mg | Change From Baseline in Urine Specific Gravity | 0.0036 Ratio of urine density to water density | Standard Deviation 0.00825 |
Primary
Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety population comprised of all participants who have received at least one dose of study treatment. This population was used for the safety analyses.
Time frame: From the day of first dose to 39 days
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 0 Participants |
| Placebo | Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| GSK2982772 60 mg | Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| GSK2982772 60 mg | Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 1 Participants |
| GSK2982772 120 mg | Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 0 Participants |
| GSK2982772 120 mg | Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| GSK2982772 240 mg | Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 0 Participants |
| GSK2982772 240 mg | Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
Primary
Number of Participants With Abnormal Neurological Examinations of TID Doses for One Day of GSK2982772
Neurological examinations including: mental status, gait, balance, coordination, cranial nerves, motor power, reflexes, and sensory system (light touch and pain) were assessed in participants specified time points.
Time frame: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Abnormal Neurological Examinations of TID Doses for One Day of GSK2982772 | 0 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Neurological Examinations of TID Doses for One Day of GSK2982772 | 0 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Neurological Examinations of TID Doses for One Day of GSK2982772 | 0 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Neurological Examinations of TID Doses for One Day of GSK2982772 | 0 Participants |
Primary
Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry
Continuous cardiac telemetry was performed and number of participants with abnormal clinically significant and not clinically significant values are presented.
Time frame: Up to 24 hours at each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Abnormal-clinically significant | 0 Participants |
| Placebo | Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Abnormal-not clinically significant | 1 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Abnormal-clinically significant | 0 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Abnormal-not clinically significant | 0 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Abnormal-not clinically significant | 0 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Abnormal-clinically significant | 0 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Abnormal-clinically significant | 0 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry | Abnormal-not clinically significant | 0 Participants |
Primary
Number of Participants With Abnormal Urinalysis Results by Dipstick Method
Urine samples were collected to assess urine bilirubin, urine glucose, urine ketones, urine occult blood, urine protein and urine urobilinogen by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine bilirubin, urine occult blood, urine glucose, urine ketones, urine protein and urine urobilinogen can be read as negative (-) and trace (+-) indicating proportional concentrations in the urine sample.
Time frame: At 72 hours of each Treatment Period
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Bilirubin, 72 hours, negative | 12 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Glucose, 72 hours, negative | 12 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Ketones, 72 hours, negative | 12 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Occult Blood, 72 hours, negative | 12 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Protein, 72 hours, negative | 12 Participants |
| Placebo | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Urobilinogen, 72 hours, trace | 12 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Urobilinogen, 72 hours, trace | 12 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Occult Blood, 72 hours, negative | 12 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Bilirubin, 72 hours, negative | 12 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Ketones, 72 hours, negative | 12 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Glucose, 72 hours, negative | 12 Participants |
| GSK2982772 60 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Protein, 72 hours, negative | 12 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Glucose, 72 hours, negative | 12 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Ketones, 72 hours, negative | 12 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Occult Blood, 72 hours, negative | 12 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Urobilinogen, 72 hours, trace | 12 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Protein, 72 hours, negative | 12 Participants |
| GSK2982772 120 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Bilirubin, 72 hours, negative | 12 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Protein, 72 hours, negative | 12 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Urobilinogen, 72 hours, trace | 12 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Glucose, 72 hours, negative | 12 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Occult Blood, 72 hours, negative | 12 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Bilirubin, 72 hours, negative | 12 Participants |
| GSK2982772 240 mg | Number of Participants With Abnormal Urinalysis Results by Dipstick Method | Ketones, 72 hours, negative | 12 Participants |
Secondary
Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24) and AUC over each dose: AUC(0-7), AUC (7-14) and AUC (14-24) after the administration of TID doses of GSK2982772. Pharmacokinetic analysis was conducted using standard non-compartmental methods. All participants in the safety population for whom a pharmacokinetic sample has been obtained and analyzed was included in the pharmacokinetic population.
Time frame: Pre-dose, 20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours, 7 hours 20 minutes, 7 hours 40 minutes, 8, 8.5, 9, 10, 12, 14 hours, 14 hours 20 minutes, 14 hours 40 minutes, 15, 15.5, 16, 17, 19, 22 and 24 hours post-dose at each Treatment Period
Population: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (14-24), TID dose 3, n=12, 12, 12 | 4.919 Hours*microgram per milliliter | Geometric Coefficient of Variation 24.9 |
| Placebo | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (0-7), TID dose 1, n=10, 10, 7 | 3.804 Hours*microgram per milliliter | Geometric Coefficient of Variation 22.4 |
| Placebo | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (7-14), TID dose 2, n=10, 6, 8 | 4.684 Hours*microgram per milliliter | Geometric Coefficient of Variation 18.7 |
| Placebo | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (0-24), n=12, 12, 12 | 13.153 Hours*microgram per milliliter | Geometric Coefficient of Variation 22.4 |
| GSK2982772 60 mg | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (0-7), TID dose 1, n=10, 10, 7 | 6.553 Hours*microgram per milliliter | Geometric Coefficient of Variation 22.6 |
| GSK2982772 60 mg | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (7-14), TID dose 2, n=10, 6, 8 | 9.200 Hours*microgram per milliliter | Geometric Coefficient of Variation 18.6 |
| GSK2982772 60 mg | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (0-24), n=12, 12, 12 | 25.779 Hours*microgram per milliliter | Geometric Coefficient of Variation 17.7 |
| GSK2982772 60 mg | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (14-24), TID dose 3, n=12, 12, 12 | 10.105 Hours*microgram per milliliter | Geometric Coefficient of Variation 20.8 |
| GSK2982772 120 mg | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (7-14), TID dose 2, n=10, 6, 8 | 20.875 Hours*microgram per milliliter | Geometric Coefficient of Variation 20.5 |
| GSK2982772 120 mg | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (0-7), TID dose 1, n=10, 10, 7 | 10.854 Hours*microgram per milliliter | Geometric Coefficient of Variation 26.6 |
| GSK2982772 120 mg | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (14-24), TID dose 3, n=12, 12, 12 | 23.602 Hours*microgram per milliliter | Geometric Coefficient of Variation 16.8 |
| GSK2982772 120 mg | Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772 | AUC (0-24), n=12, 12, 12 | 54.960 Hours*microgram per milliliter | Geometric Coefficient of Variation 19 |
Secondary
Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772
Blood samples were collected from participants at indicated time points and analyzed for Cmax and observed trough drug plasma concentrations: C0, C7, C14 and C24 after the administration of TID doses of GSK2982772.
Time frame: Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment Period
Population: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 1, n=12, 12, 12 | 1.187 Micrograms per milliliter | Geometric Coefficient of Variation 16.2 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 2, n=12, 12, 12 | 1.322 Micrograms per milliliter | Geometric Coefficient of Variation 34.2 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 3, n=12, 12, 12 | 1.076 Micrograms per milliliter | Geometric Coefficient of Variation 32.9 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C7, TID dose 1, n=12, 12, 12 | 0.149 Micrograms per milliliter | Geometric Coefficient of Variation 55.3 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C14, TID dose 2, n=12, 12, 12 | 0.175 Micrograms per milliliter | Geometric Coefficient of Variation 44 |
| Placebo | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C24, TID dose 3, n=12, 12, 12 | 0.107 Micrograms per milliliter | Geometric Coefficient of Variation 44.7 |
| GSK2982772 60 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C24, TID dose 3, n=12, 12, 12 | 0.229 Micrograms per milliliter | Geometric Coefficient of Variation 53.3 |
| GSK2982772 60 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 1, n=12, 12, 12 | 2.003 Micrograms per milliliter | Geometric Coefficient of Variation 27.7 |
| GSK2982772 60 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C7, TID dose 1, n=12, 12, 12 | 0.344 Micrograms per milliliter | Geometric Coefficient of Variation 41.5 |
| GSK2982772 60 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C14, TID dose 2, n=12, 12, 12 | 0.439 Micrograms per milliliter | Geometric Coefficient of Variation 44.6 |
| GSK2982772 60 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 2, n=12, 12, 12 | 2.727 Micrograms per milliliter | Geometric Coefficient of Variation 21.2 |
| GSK2982772 60 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 3, n=12, 12, 12 | 2.378 Micrograms per milliliter | Geometric Coefficient of Variation 17.8 |
| GSK2982772 120 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 2, n=12, 12, 12 | 5.516 Micrograms per milliliter | Geometric Coefficient of Variation 21.1 |
| GSK2982772 120 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 3, n=12, 12, 12 | 5.120 Micrograms per milliliter | Geometric Coefficient of Variation 13.2 |
| GSK2982772 120 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C24, TID dose 3, n=12, 12, 12 | 0.543 Micrograms per milliliter | Geometric Coefficient of Variation 47.6 |
| GSK2982772 120 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C7, TID dose 1, n=12, 12, 12 | 0.878 Micrograms per milliliter | Geometric Coefficient of Variation 54.7 |
| GSK2982772 120 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | Cmax, TID dose 1, n=12, 12, 12 | 3.038 Micrograms per milliliter | Geometric Coefficient of Variation 27.5 |
| GSK2982772 120 mg | Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772 | C14, TID dose 2, n=12, 12, 12 | 0.999 Micrograms per milliliter | Geometric Coefficient of Variation 26.5 |
Secondary
Terminal Half Life (t1/2) After the Third TID Dose for One Day of GSK2982772
Blood samples were collected from participants at indicated time points and t1/2 was analyzed after the administration of third TID dose of GSK2982772.
Time frame: Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment Period
Population: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Terminal Half Life (t1/2) After the Third TID Dose for One Day of GSK2982772 | 5.883 Hours | Geometric Coefficient of Variation 52.5 |
| GSK2982772 60 mg | Terminal Half Life (t1/2) After the Third TID Dose for One Day of GSK2982772 | 7.206 Hours | Geometric Coefficient of Variation 31.9 |
| GSK2982772 120 mg | Terminal Half Life (t1/2) After the Third TID Dose for One Day of GSK2982772 | 6.624 Hours | Geometric Coefficient of Variation 51.8 |
Secondary
Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772
Blood samples were collected from participants at indicated time points and Tmax was analyzed after the administration of TID doses of GSK2982772.
Time frame: Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment Period
Population: Pharmacokinetic Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 2 | 1.750 Hours |
| Placebo | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 1 | 2.000 Hours |
| Placebo | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 3 | 2.500 Hours |
| GSK2982772 60 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 2 | 2.500 Hours |
| GSK2982772 60 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 1 | 1.750 Hours |
| GSK2982772 60 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 3 | 3.000 Hours |
| GSK2982772 120 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 1 | 2.000 Hours |
| GSK2982772 120 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 3 | 3.000 Hours |
| GSK2982772 120 mg | Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772 | TID dose 2 | 2.000 Hours |