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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1: Placebo TID then 60 TID then 120 TID then 240 TID | Experimental | The eligible subjects in this arm will receive placebo TID in TP1, GSK2982772 60 mg TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject. |
|
| Sequence 2: 60 TID then Placebo TID then 120 TID then 240 TID | Experimental | The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, placebo TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject. |
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| Sequence 3: 60 TID then 120 TID then Placebo TID then 240 TID | Experimental | The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, placebo TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2982772 | Drug | GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From the day of first dose to 39 days |
| 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. | Baseline (Day -1) and at 72 hours at each treatment period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Fukuoka | 812-0025 | Japan |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33165774 | Derived | Tompson DJ, Davies C, Scott NE, Cannons EP, Kostapanos M, Gross AS, Powell M, Ino H, Shimamura R, Ogura H, Nagakubo T, Igarashi H, Nakano A. Comparison of the Pharmacokinetics of RIPK1 Inhibitor GSK2982772 in Healthy Western and Japanese Subjects. Eur J Drug Metab Pharmacokinet. 2021 Jan;46(1):71-83. doi: 10.1007/s13318-020-00652-2. |
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Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
A total of 13 healthy male Japanese participants were enrolled in the study to receive GSK2982772 and PBO from a single center in Japan
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
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Sequence A: PBO TID /60mg TID /120mg TID /240mg TID | Participants in this arm received PBO TID in treatment period (TP) 1, GSK2982772 60 milligram (mg) TID in TP2, GSK2982772 120 mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant. |
| FG001 | Treatment Sequence B: 60mg TID /PBO TID /120mg TID /240mg TID | Participants in this arm received GSK2982772 60 mg TID in TP1, PBO TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant. |
| FG002 | Treatment Sequence C: 60mg TID/ 120mg TID/ PBO TID/ 240mg TID | Participants in this arm received GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, PBO TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant. |
| FG003 | Treatment Sequence D: 60mg TID /120mg TID /240mg TID /PBO TID | Participants in this arm received GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, GSK2982772 240 mg TID in TP3 and PBO TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1, 4 Days |
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| Period 1, Wash-out, at Least 3 Days |
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| Period 2, 4 Days |
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| Period 2, Wash-out, at Least 3 Days |
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| Period 3, 4 Days |
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| Period 3,Wash-out, at Least 3 Days |
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| Period 4, 4 Days |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Safety Population. | Posted | Count of Participants | Participants | From the day of first dose to 39 days |
|
Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Alanine aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 27, 2018 | Aug 7, 2019 | Prot_001.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 11, 2018 | Aug 2, 2019 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000708951 | GSK2982772 |
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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.
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It is a double-blinded study, where the subjects, investigators and the site-staff will be blinded.
| Sequence 4: 60 TID then 120 TID then 240 TID then Placebo TID | Experimental | The eligible subjects in this arm will receive GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, GSK2982772 240 mg TID in TP3 and placebo TID in TP4. GSK2982772 or placebo will be administered at 0 hour (the first dosing), 7 hours (the second dosing) and 14 hours (the third dosing) on Day 1 in each TP. Subjects will fast overnight for 8 hours before first dose. Each TP will be followed by a washout period of at least 7 days, for each subject. |
|
| Placebo | Drug | Placebo matching GSK2982772 will be available as white to almost white, round, film coated tablets to be administered via oral route. |
|
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. |
| Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 72 hours at each Treatment Period |
| 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. | At 72 hours of each Treatment Period |
| 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. | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
| 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. | Up to 24 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each treatment period |
| 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. | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
| 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. | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
| 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 |
| 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. | 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 |
| 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. | 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 |
| 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. | 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 |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | Participants |
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Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP. |
| OG001 | GSK2982772 60 mg | Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP. |
| OG002 | GSK2982772 120 mg | Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP. |
| OG003 | GSK2982772 240 mg | Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP. |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Millimoles per liter | Baseline (Day -1) and at 72 hours at each treatment period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Grams per liter | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | International units per liter | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population | Posted | Mean | Standard Deviation | Units per liter | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Micromoles per liter | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Milligrams per liter | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Percentage of red blood cells in blood | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Grams per liter | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Picograms | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Femtoliters | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | 10^12 cells per liter | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Ratio of Reticulocytes to Erythrocytes | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | 10^9 cells per liter | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Percentage of cells in leukocytes | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | pH | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Ratio of urine density to water density | Baseline (Day -1) and at 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Count of Participants | Participants | At 72 hours of each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Milliseconds | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Count of Participants | Participants | Up to 24 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each treatment period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Mean | Standard Deviation | Degrees Celsius | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
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| 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. | Safety Population. | Posted | Count of Participants | Participants | Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment Period |
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| 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. | Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | 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 |
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| 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. | Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Geometric Mean | Geometric Coefficient of Variation | Micrograms per milliliter | 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 |
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| 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. | Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours | 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 |
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| 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. | Pharmacokinetic Population. | Posted | Median | Full Range | Hours | 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 |
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| 0 |
| 12 |
| 0 |
| 12 |
| 0 |
| 12 |
| EG001 | GSK2982772 60 mg | Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP | 0 | 12 | 0 | 12 | 1 | 12 |
| EG002 | GSK2982772 120 mg | Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP | 0 | 12 | 0 | 12 | 0 | 12 |
| EG003 | GSK2982772 240 mg | Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP | 0 | 12 | 0 | 12 | 0 | 12 |
| Aspartate aminotransferase increased | Investigations | MedDRA 21.0 | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| Calcium |
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| Cholesterol |
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| Chloride |
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| HDL Cholesterol |
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| Potassium |
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| LDL Cholesterol |
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| Phosphate |
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| Sodium |
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| Triglycerides |
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| Urea |
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| Protein |
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| ALT |
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| AST |
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| CK |
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| GGT |
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| LDH |
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| Bilirubin |
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| Creatinine |
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| Urate |
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| Leukocytes |
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| Monocytes/Leukocytes |
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| Lymphocytes/Leukocytes |
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| Eosinophils/Leukocytes |
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| Basophils/Leukocytes |
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| Glucose, 72 hours, negative |
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| Ketones, 72 hours, negative |
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| Occult Blood, 72 hours, negative |
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| Protein, 72 hours, negative |
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| Urobilinogen, 72 hours, trace |
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| 7 hours |
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| 14 hours |
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| 24 hours |
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| 48 hours |
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| 72 hours |
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| PR interval, 7 hours |
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| PR interval, 14 hours |
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| PR interval, 24 hours |
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| PR interval, 48 hours |
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| PR interval, 72 hours |
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| QRS duration, 2 hours |
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| QRS duration, 7 hours |
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| QRS duration, 14 hours |
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| QRS duration, 24 hours |
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| QRS duration, 48 hours |
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| QRS duration, 72 hours |
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| QT interval, 2 hours |
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| QT interval, 7 hours |
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| QT interval, 14 hours |
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| QT interval, 24 hours |
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| QT interval, 48 hours |
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| QT interval, 72 hours |
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| QTcF interval, 2 hours |
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| QTcF interval, 7 hours |
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| QTcF interval, 14 hours |
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| QTcF interval, 24 hours |
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| QTcF interval, 48 hours |
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| QTcF interval, 72 hours |
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| Abnormal-clinically significant |
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| DBP, 7 hours |
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| DBP, 14 hours |
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| DBP, 24 hours |
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| DBP, 48 hours |
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| DBP, 72 hours |
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| SBP, 2 hours |
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| SBP, 7 hours |
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| SBP, 14 hours |
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| SBP, 24 hours |
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| SBP, 48 hours |
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| SBP, 72 hours |
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| 7 hours |
|
| 14 hours |
|
| 24 hours |
|
| 48 hours |
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| 72 hours |
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| 7 hours |
|
| 14 hours |
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| 24 hours |
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| 48 hours |
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| 72 hours |
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| AUC (0-7), TID dose 1, n=10, 10, 7 |
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| AUC (7-14), TID dose 2, n=10, 6, 8 |
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| AUC (14-24), TID dose 3, n=12, 12, 12 |
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| Cmax, TID dose 2, n=12, 12, 12 |
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| Cmax, TID dose 3, n=12, 12, 12 |
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| C0, TID dose 1, n=0, 0, 0 |
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| C7, TID dose 1, n=12, 12, 12 |
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| C14, TID dose 2, n=12, 12, 12 |
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| C24, TID dose 3, n=12, 12, 12 |
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| TID dose 3 |
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