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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-002370-48 | EudraCT Number |
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| Name | Class |
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| Quotient Sciences | INDUSTRY |
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Previous clinical studies of immediate release (IR) formulations of GSK2982772 resulted in a high peak to trough ratio of GSK2982772. Additionally, the short half-life for GSK2982772 (approximately 2 to 3 hours) necessitates twice a daily (BID) or thrice daily (TID) dosing of an IR formulation. As a result, MR formulations using a polymer matrix approach with minitablets in capsule and MR tablet formulations were investigated. The emerging PK data of the MR formulations investigated to date have demonstrated that a once daily (QD) PK profile can be achieved in the fasted state but the polymer matrix formulation is susceptible to food effects when administered with a high fat breakfast. The purpose of this study is to evaluate MR prototype coated tablet formulations. This study will evaluate the PK of MR prototype coated tablet formulations of GSK2982772. The study is divided into two parts; Part A and Part B. The MR tablet coating used in Part A and the initial periods of Part B will have an aperture drilled into the enteric coating of either side of the tablet. This allows some drug release to commence in the stomach whilst providing controlled release throughout the gastrointestinal (GI) tract. In Part B only, a new investigational medicinal product (IMP) will be manufactured to allow comparison of the tablet coating either with apertures (i.e., drilled) or without apertures (i.e., full coat/non drilled). Part A will be a 6-period, 6-way fixed sequence design, up to 4 MR tablet prototype coated formulations will be evaluated in fasted state at 240 milligrams (mg). Periods 1, 2 and 3 will evaluate MR1, IR tablet and MR2 respectively. Periods 4, 5 and 6 will be flexible and the dosing regimen will be dependent on the outcome of Periods 1 to 3. In addition, the impact of food (high fat meal, standard breakfast or administration 30 or 60 minutes before a standard breakfast) on selected MR prototype coated tablet formulations may also be evaluated in Period 4, 5 or 6 of Part A. Each inpatient period for MR regimens (Periods 1, 3, 4 to 6) will consist of 4 days and 3 nights, and the inpatient period for the IR tablet (Period 2) will consist of 3 days and 2 nights. There will be a minimum washout of 7 days between doses, and a follow-up visit will occur at 7 to 9 days after the last study treatment. The Part B of the study will be a 7-period fixed sequence which will evaluate the selected MR prototype coated tablet formulation(s) at different tablet strengths or as multiple unit doses and with or without apertures in the tablet coatings. There will be an interim review after each period 1 to 5 of Part B to select the dose level, formulation and prandial status for each subsequent period. An interim data review after Part B Period 6 will determine if optional Period 7 is required and the dose level, dosing time (morning or evening), formulation and prandial status for that period. Each inpatient period will consist of a 4-day and 3-night with a minimum of 7 days washout between doses. A follow-up visit will occur at 7 to 9 days after the last study treatment. Approximately 33 subjects will be enrolled in the study. The total duration for Part A will be approximately 10-12 weeks and 10-14 weeks for Part B (including screening period of approximately 4 weeks).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Subjects in Part A | Experimental | Subjects in Part A will receive GSK2982772 MR (Period 1, 3, 4, 5 and 6) and GSK2982772 IR (Period 2). |
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| Subjects in Part B | Experimental | Subjects in Part B will receive GSK2982772 MR. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK2982772 Modified Release | Drug | GSK2982772 MR will be available as MR prototype coated tablet with unit dose strength of 240 mg in Part A. In Part B, GSK2982772 MR prototype coated tablet with unit dose strength of 120 mg (may be changed following interim review of Part B) will be administered by subjects. GSK2982772 MR will be administered orally with 240 milliliter (mL) of water. |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK2982772 240 mg in IR Formulation | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were analyzed using standard non-compartmental analysis. Participants in the 'Safety Population (all participants who received at least one dose of study treatment)' for whom a PK sample was obtained and analyzed were part of PK Population. | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
| Part A: AUC(0-inf) of GSK2982772 240 mg in MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points for PK analysis. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: AUC(0-inf) of GSK2982772 240 mg in MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points for PK analysis. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
| Part A: AUC(0-t) of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis. |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a clinical study participants, 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 may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events that may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before. |
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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 | Nottingham | NG11 6JS | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34988780 | Derived | Tompson D, Whitaker M, Pan R, Johnson G, Fuller T, Zann V, McKenzie L, Abbott-Banner K, Hawkins S, Powell M. Development of a Once-Daily Modified-Release Formulation for the Short Half-Life RIPK1 Inhibitor GSK2982772 using DiffCORE Technology. Pharm Res. 2022 Jan;39(1):153-165. doi: 10.1007/s11095-021-03124-7. Epub 2022 Jan 5. |
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IPD for this study will be made available via the Clinical Study Data Request site.
IPD will be made available, within 6 months of publishing the results of the primary endpoints of the study.
Access is provided, after a research proposal is submitted and has received approval from the 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 can be granted, when justified for up to another 12 months.
A total of 33 participants were enrolled in this study. In Part A, 16 participants were enrolled but 1 replacement participant was added (total=17). Participants from Part A did not continue to Part B. In Part B, 16 participants were enrolled.
This was an open-label, 2-part (Part A & B), single dose study in healthy participants to assess modified release (MR) prototype coated tablet formulations of GSK2982772 compared to an immediate release reference tablet formulation.
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| ID | Title | Description |
|---|---|---|
| FG000 | MR 12h Fast/IR Fast/MR18h Fast/MR 18h Fed/MR 12h Fed/MR16hFast | Participants in Part A received a single dose of 240 milligrams (mg) GSK2982772 MR-12 hour (h) tablet (80 percent [%] release in 12 hours) in fasted (fast) state in Period 1 followed by a single dose of GSK2982772 240 mg (8x30mg) immediate release (IR) tablet in fasted state in Period 2 followed by a single dose of 240 mg GSK2982772 MR-18h (80% release in 18 hours) tablet in fasted state in Period 3. In Period 4, participants received a single dose of 240 mg GSK2982772 MR-18h tablet after a high-fat meal (fed state) followed by a single dose of MR-12h tablet after a high fat meal (fed state) in Period 5. In Period 6, participants received a single dose of 240 mg of GSK2982772 of MR-16h tablet (80% release in 16 hours) in a fasted state. There was a washout of 7 days between each treatment period. All doses were administered orally with 240 milliliters (mL) of water. |
| FG001 | MR 480Fast/960Fast/480Fed/120Fast/480 Fed (Ent)/480 Fed(Std) | Participants in Part B received a single dose of 480 mg GSK2982772 MR-16h tablet (80% release in 16 hours) in a fasted state in Period 1 followed by a single dose 960 mg GSK2982772 MR-16h tablet in a fasted state in Period 2 followed by a single dose of 480 mg GSK2982772 MR-16h tablet after a high-fat meal (fed state) in Period 3. In Period 4, participants received a single dose of 120 mg GSK2982772 MR-16h tablet in a fasted state followed by a single dose of 480 mg GSK2982772 MR-16h enteric (Ent) coated tablet after a high-fat meal (fed state) in Period 5. In Period 6, participants received a single dose of 480 mg GSK2982772 MR-16h tablet after a standard meal (fed state).There was a washout of 7 days between each treatment period. All doses were administered orally with 240 mL of water. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
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| Part A, Period 1 (4 Days) |
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| Part A, Washout Period 1 (7 Days) |
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| Part A, Period 3 (4 Days) |
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| Part A, Washout Period 4 (7 Days) |
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| Part A, Period 5 (4 Days) |
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| Part A, Washout Period 5 (7 Days) |
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| Part A, Period 6 (4 Days) |
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| Part B, Period 1 (4 Days) |
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| Part B, Washout Period 1 (7 Days) |
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| Part B, Period 2 (4 Days) |
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| Part B, Period 3 (4 Days) |
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| Part B, Washout Period 3 (7 Days) |
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| Part B, Washout Period 4 (7 Days) |
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| Part B, Period 5 (4 Days) |
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| Part B, Washout Period 5 (7 Days) |
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| Part B, Period 6 (4days) |
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| ID | Title | Description |
|---|---|---|
| BG000 | MR 12h Fast/IR Fast/MR18h Fast/MR 18h Fed/MR 12h Fed/MR16hFast | Participants in Part A received a single dose of 240 milligrams (mg) GSK2982772 MR-12 hour (h) tablet (80 percent [%] release in 12 hours) in fasted (fast) state in Period 1 followed by a single dose of GSK2982772 240 mg (8x30mg) immediate release (IR) tablet in fasted state in Period 2 followed by a single dose of 240 mg GSK2982772 MR-18h (80% release in 18 hours) tablet in fasted state in Period 3. In Period 4, participants received a single dose of 240 mg GSK2982772 MR-18h tablet after a high-fat meal (fed state) followed by a single dose of MR-12h tablet after a high fat meal (fed state) in Period 5. In Period 6, participants received a single dose of 240 mg of GSK2982772 of MR-16h tablet (80% release in 16 hours) in a fasted state. There was a washout of 7 days between each treatment period. All doses were administered orally with 240 milliliters (mL) of water. |
| Units | Counts |
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| 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 | Part A: Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK2982772 240 mg in IR Formulation | Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were analyzed using standard non-compartmental analysis. Participants in the 'Safety Population (all participants who received at least one dose of study treatment)' for whom a PK sample was obtained and analyzed were part of PK Population. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
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Non-serious AEs and SAEs were collected up to Day 67 for Part A and up to Day 68 for Part B
Non-serious AEs and SAEs were collected in 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 | Part A: IR 240 mg Fasted | Participants received a single oral dose of 240 mg (8x30mg) GSK2982772 IR tablet in a fasted state |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA 22.0 | 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 |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 18, 2019 | Mar 12, 2020 | SAP_000.pdf |
| Prot | Yes | No | No | Study Protocol | Apr 10, 2019 | Mar 25, 2020 | Prot_001.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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Part A will be a 6-period, 6-way fixed sequence design, in which up to 4 MR tablet prototype coated formulation will be evaluated, following single dose administration (240 mg) in fasted or fed state. There will be a minimum 7-day washout between doses. Part B of the study is optional. Following the final period of Part A, there will be an interim review to determine whether to proceed with optional Part B, and if so, the formulations and tablet strengths to be investigated in Part B. The Part B of the study will be a 7-period fixed sequence which will evaluate the selected MR prototype coated tablet formulation(s) at different tablet strengths or as multiple unit doses.
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There will be no masking as this is an open-label study.
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| GSK2982772 Immediate Release | Drug | In part A, GSK2982772 IR tablet will be available with unit dose strength of 30 mg and the total dose administered by subjects will be 240 mg (8 tablets of dose strength 30 mg) orally with 240 mL of water |
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| Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: AUC(0-t) of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Area Under the Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
| Part A: AUC(0-24) of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose |
| Part A: AUC(0-24) of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose |
| Part A: Maximum Observed Concentration (Cmax) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
| Part A: Cmax of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Cmax of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Concentration at 24 Hours Post-dose (C24h) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis. | 24 hours post-dose |
| Part A: C24h of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis. | 24 hours post-dose |
| Part A: C24h of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis. | 24 hours post-dose |
| Part A: Time to Cmax (Tmax) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
| Part A: Tmax of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Tmax of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Terminal Half-life (t1/2) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
| Part A: t1/2 of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours |
| Part A: t1/2 of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours |
| Part B: AUC(0-inf) of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for AUC(0-inf). PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: AUC(0-t) of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for AUC(0-t). PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: Cmax of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose post-dose |
| Part B: C24h of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis. | 24 hours post-dose |
| Part B: Tmax of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: t1/2 of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Relative Bioavailability in Fed Versus Fasted Conditions (FrelFE) Based on AUC(0-inf) of GSK2982772 for MR Coated Tablet Formulation | Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR Fed/ Geometric mean of AUC(0-inf) of MR Fasted multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: FrelFE Based on AUC(0-t) of GSK2982772 for MR Coated Tablet Formulation | Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772. Frel for AUC(0-t) was calculated as Geometric mean of AUC(0-t) of MR Fed/Geometric mean of AUC(0-t) of MR Fasted multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: FrelFE Based on Cmax of GSK2982772 for MR Coated Tablet Formulation | Blood samples were collected at indicated time points for analysis of FrelFE based on Cmax of GSK2982772. Frel for Cmax was calculated as Geometric mean of Cmax of MR Fed/Geometric mean of Cmax of MR Fasted multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: FrelFE of GSK2982772 Based on AUC(0-inf) for MR Coated Tablet Formulation in Fed vs Fasted State | Blood samples were collected at indicated time points for analysis of FrelFE based on AUC(0-inf) of GSK2982772. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR Fed/ Geometric mean of AUC(0-inf) of MR Fasted multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: FrelFE of GSK2982772 Based on AUC (0-t) for MR Coated Tablet Formulation in Fed vs Fasted State | Blood samples were collected at indicated time points for analysis of FrelFE based on AUC (0-t) of GSK2982772. FrelFE for AUC (0-t) was calculated as Geometric mean of AUC (0-t) of MR Fed/ Geometric mean of AUC (0-t) of MR Fasted multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: FrelFE of GSK2982772 Based on Cmax for MR Coated Tablet Formulation in Fed vs Fasted State | Blood samples were collected at indicated time points for analysis of FrelFE based on Cmax of GSK2982772. FrelFE for Cmax was calculated as Geometric mean of Cmax of MR Fed/ Geometric mean of Cmax of MR Fasted multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: Frel of GSK2982772 Based on AUC (0-inf) for MR Coated Tablet Formulation in Fasted State | Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC (0-inf) of GSK2982772. Frel (dose) for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MR formulation (test dose) Fasted/ Geometric mean of AUC (0-inf) of MR Fasted formulation (reference dose) multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: Frel of GSK2982772 Based on AUC (0-t) for MR Coated Tablet Formulation in Fasted State | Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC(0-t) of GSK2982772. Frel (dose) for AUC(0-t) was calculated as Geometric mean of AUC(0-t) of MR formulation (test dose) Fasted/ Geometric mean of AUC(0-t) of MR Fasted formulation (reference dose) multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part B: Frel of GSK2982772 Based on AUC (0-24) for MR Coated Tablet Formulation in Fasted State | Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC(0-24) of GSK2982772. Frel (dose) for AUC(0-24) was calculated as Geometric mean of AUC(0-24) of MR formulation (test dose) Fasted/Geometric mean of AUC(0-24) of MR Fasted formulation (reference dose) multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose |
| Part B: Frel of GSK2982772 Based on Cmax for MR Coated Tablet Formulation in Fasted State | Blood samples were collected at indicated time points for analysis of Frel dose. Frel for Cmax was calculated as Geometric mean of Cmax of MR formulation (test) Fasted/ Geometric mean of Cmax of MR Fasted Formulation (reference dose) multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Relative Bioavailability (Frelformulation) Based on AUC (0-inf) of GSK2982772 240 mg | Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC(0-inf) of GSK2982772 in fasted state. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR formulation (test) Fasted/ Geometric mean of AUC(0-inf) of Fasted of IR Formulation (reference) multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
| Part A: Frelformulation Based on AUC (0-t) of GSK2982772 for MR Coated Tablet Formulation (240 mg) | Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 in fasted state. Frel for AUC (0-t) was calculated as Geometric mean of AUC(0-t) of MR Fasted formulation (test) / Geometric mean of AUC(0-t) of Fasted of IR Formulation (reference) multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours |
| Part A: Frelformulation Based on AUC(0-24) of GSK2982772 for MR Coated Tablet Formulation (240 mg) | Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 in fasted state. Frel for AUC(0-24) was calculated as Geometric mean of AUC(0-24) of MR Fasted formulation (test) / Geometric mean of AUC(0-24) of Fasted of IR Formulation (reference) multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours |
| Part A: Frelformulation Based on Cmax of GSK2982772 for MR Coated Tablet Formulation (240 mg) | Blood samples were collected at indicated time points for analysis of Frelformulation based on Cmax of GSK2982772 in fasted state. Frel for Cmax was calculated as Geometric mean of Cmax of MR Fasted formulation (test) / Geometric mean of Cmax of Fasted Formulation of IR formulation (reference) multiplied by 100. | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours |
| Up to Day 67 |
| Part A: Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria | Clinical chemistry parameters with PCI values:albumin (low: <30 millimoles per liter[mmol/L]), Alanine transaminase (ALT) (high: >=2xupper limit of normal [ULN]), Aspartate Aminotransferase(AST) (high: >=2xULN), Alkaline phosphatase(ALP) (high:>=2xULN), calcium(low: <2 mmol/L, high: >2.75 mmol/L),creatinine (high: >44.2 mmol/L),glucose (low: <3 mmol/L,high: >9 mmol/L), potassium (low: <3 mmol/L,high: >5.5 mmol/L),sodium (low: <130 mmol/L,high: >150 mmol/L),total bilirubin(high :>= 1.5xULN). Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High),or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the participants has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Data for worst-case post-Baseline has been reported. | Up to Day 67 |
| Part A: Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria | Hematology parameters with PCI ranges: hematocrit (high: >0.54 percentage of red blood cells), hemoglobin (high: >180 grams per liter [g/L]), lymphocytes (low: <0.8*giga cells per liter [10^9/L]), total neutrophil count (low: <1.5*10^9/L), platelet count (low: <100*10^9/L and high: >550*10^9/L), and while blood cell (WBC) count (low: <3*10^9/L and high: >20*10^9/L). Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Data for worst-case post-Baseline has been reported. | Up to Day 67 |
| Part A: Number of Participants With Abnormal Urinalysis Dipstick Results | Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination was performed abnormal data for red blood cells (RBC): 1-9 High potential field (HPF) and WBC: 1-9/ HPF; WBC: 10-50/HPF has been presented. | Day 2 (post-dose) |
| Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in IR Formulation | SBP and DBP were measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours |
| Part A: Change From Baseline in SBP and DBP in MR Formulation | SBP and DBP were measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours |
| Part A: Change From Baseline in Heart Rate in IR Formulation | Heart rate was measured in a semi-supine position after 5 minutes of rest of participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours |
| Part A: Change From Baseline in Heart Rate in MR Formulation | Heart rate was measured in a semi-supine position after 5 minutes of rest of participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours |
| Part A: Change From Baseline in Respiration Rate in IR Formulation | Respiratory rate was measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours |
| Part A: Change From Baseline in Respiration Rate in MR Formulation | Respiratory rate was measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours |
| Part A: Change From Baseline in Body Temperature in IR Formulation | Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours |
| Part A: Change From Baseline in Body Temperature in MR Formulation | Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours |
| Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in IR Formulation | Single 12-lead ECGs were obtained using an automated ECG machine that calculated PR, QRS, QT and Corrected QT (QTc) intervals. ECG measurements were performed in a semi-supine or supine position. Number of participants with abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst-case post-Baseline has been reported. | Up to Day 67 |
| Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in MR Formulation | Single 12-lead ECGs were obtained using an automated ECG machine that calculated PR, QRS, QT and Corrected QT (QTc) intervals. ECG measurements were performed in a semi-supine or supine position. Number of participants with abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst-case post-Baseline has been reported. | Up to Day 67 |
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| BG001 | MR 480Fast/960Fast/480Fed/120Fast/480 Fed (Ent)/480 Fed(Std) | Participants in Part B received a single dose of 480 mg GSK2982772 MR-16h tablet (80% release in 16 hours) in a fasted state in Period 1 followed by a single dose 960 mg GSK2982772 MR-16h tablet in a fasted state in Period 2 followed by a single dose of 480 mg GSK2982772 MR-16h tablet after a high-fat meal (fed state) in Period 3. In Period 4, participants received a single dose of 120 mg GSK2982772 MR-16h tablet in a fasted state followed by a single dose of 480 mg GSK2982772 MR-16h enteric (Ent) coated tablet after a high-fat meal (fed state) in Period 5. In Period 6, participants received a single dose of 480 mg GSK2982772 MR-16h tablet after a standard meal (fed state).There was a washout of 7 days between each treatment period. All doses were administered orally with 240 mL of water. |
| BG002 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Units | Counts |
|---|---|
| Participants |
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| Primary | Part A: AUC(0-inf) of GSK2982772 240 mg in MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points for PK analysis. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Only those participants with data available at specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: AUC(0-inf) of GSK2982772 240 mg in MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points for PK analysis. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Only those participants with data available at specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
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| Primary | Part A: AUC(0-t) of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: AUC(0-t) of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t). PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Area Under the Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
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| Primary | Part A: AUC(0-24) of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose |
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| Primary | Part A: AUC(0-24) of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24). PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose |
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| Primary | Part A: Maximum Observed Concentration (Cmax) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
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| Primary | Part A: Cmax of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Cmax of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Concentration at 24 Hours Post-dose (C24h) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | 24 hours post-dose |
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| Primary | Part A: C24h of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | 24 hours post-dose |
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| Primary | Part A: C24h of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | 24 hours post-dose |
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| Primary | Part A: Time to Cmax (Tmax) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Median | Full Range | Hours | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
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| Primary | Part A: Tmax of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Median | Full Range | Hours | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Tmax of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Median | Full Range | Hours | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Terminal Half-life (t1/2) of GSK2982772 240 mg for IR Formulation | Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Mean | Standard Deviation | Hours | Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose |
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| Primary | Part A: t1/2 of GSK2982772 240 mg for MR Coated Tablet Formulation | Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Mean | Standard Deviation | Hours | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours |
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| Primary | Part A: t1/2 of GSK2982772 240 mg for MR Coated Tablet Formulation After High-fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Mean | Standard Deviation | Hours | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours |
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| Primary | Part B: AUC(0-inf) of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for AUC(0-inf). PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Only those participants with data available at specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: AUC(0-t) of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for AUC(0-t). PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: Cmax of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for Cmax. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hours*microgram per milliliter | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose post-dose |
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| Primary | Part B: C24h of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for C24h. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Geometric Mean | Geometric Coefficient of Variation | Microgram per milliliter | 24 hours post-dose |
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| Primary | Part B: Tmax of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for Tmax. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. | Posted | Median | Full Range | Hours | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: t1/2 of GSK2982772 for MR Coated Tablet Formulation After a High Fat Breakfast | Blood samples were collected from participants at indicated time points and analyzed for t1/2. PK parameters were analyzed using standard non-compartmental analysis. | PK Population. Only those participants with data available at specified time point were analyzed. | Posted | Mean | Standard Deviation | Hours | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Relative Bioavailability in Fed Versus Fasted Conditions (FrelFE) Based on AUC(0-inf) of GSK2982772 for MR Coated Tablet Formulation | Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR Fed/ Geometric mean of AUC(0-inf) of MR Fasted multiplied by 100. | PK Population. Only those participants with data available at specified time points were analyzed. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: FrelFE Based on AUC(0-t) of GSK2982772 for MR Coated Tablet Formulation | Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772. Frel for AUC(0-t) was calculated as Geometric mean of AUC(0-t) of MR Fed/Geometric mean of AUC(0-t) of MR Fasted multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: FrelFE Based on Cmax of GSK2982772 for MR Coated Tablet Formulation | Blood samples were collected at indicated time points for analysis of FrelFE based on Cmax of GSK2982772. Frel for Cmax was calculated as Geometric mean of Cmax of MR Fed/Geometric mean of Cmax of MR Fasted multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: FrelFE of GSK2982772 Based on AUC(0-inf) for MR Coated Tablet Formulation in Fed vs Fasted State | Blood samples were collected at indicated time points for analysis of FrelFE based on AUC(0-inf) of GSK2982772. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR Fed/ Geometric mean of AUC(0-inf) of MR Fasted multiplied by 100. | PK Population. Only those participants with data available at specified time frame were analyzed. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: FrelFE of GSK2982772 Based on AUC (0-t) for MR Coated Tablet Formulation in Fed vs Fasted State | Blood samples were collected at indicated time points for analysis of FrelFE based on AUC (0-t) of GSK2982772. FrelFE for AUC (0-t) was calculated as Geometric mean of AUC (0-t) of MR Fed/ Geometric mean of AUC (0-t) of MR Fasted multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: FrelFE of GSK2982772 Based on Cmax for MR Coated Tablet Formulation in Fed vs Fasted State | Blood samples were collected at indicated time points for analysis of FrelFE based on Cmax of GSK2982772. FrelFE for Cmax was calculated as Geometric mean of Cmax of MR Fed/ Geometric mean of Cmax of MR Fasted multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: Frel of GSK2982772 Based on AUC (0-inf) for MR Coated Tablet Formulation in Fasted State | Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC (0-inf) of GSK2982772. Frel (dose) for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MR formulation (test dose) Fasted/ Geometric mean of AUC (0-inf) of MR Fasted formulation (reference dose) multiplied by 100. | PK Population. Only those participants with data available at specified time points were analyzed. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: Frel of GSK2982772 Based on AUC (0-t) for MR Coated Tablet Formulation in Fasted State | Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC(0-t) of GSK2982772. Frel (dose) for AUC(0-t) was calculated as Geometric mean of AUC(0-t) of MR formulation (test dose) Fasted/ Geometric mean of AUC(0-t) of MR Fasted formulation (reference dose) multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part B: Frel of GSK2982772 Based on AUC (0-24) for MR Coated Tablet Formulation in Fasted State | Blood samples were collected at indicated time points for analysis of Frel (dose) based on AUC(0-24) of GSK2982772. Frel (dose) for AUC(0-24) was calculated as Geometric mean of AUC(0-24) of MR formulation (test dose) Fasted/Geometric mean of AUC(0-24) of MR Fasted formulation (reference dose) multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose |
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| Primary | Part B: Frel of GSK2982772 Based on Cmax for MR Coated Tablet Formulation in Fasted State | Blood samples were collected at indicated time points for analysis of Frel dose. Frel for Cmax was calculated as Geometric mean of Cmax of MR formulation (test) Fasted/ Geometric mean of Cmax of MR Fasted Formulation (reference dose) multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Relative Bioavailability (Frelformulation) Based on AUC (0-inf) of GSK2982772 240 mg | Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC(0-inf) of GSK2982772 in fasted state. Frel for AUC(0-inf) was calculated as Geometric mean of AUC(0-inf) of MR formulation (test) Fasted/ Geometric mean of AUC(0-inf) of Fasted of IR Formulation (reference) multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours post-dose |
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| Primary | Part A: Frelformulation Based on AUC (0-t) of GSK2982772 for MR Coated Tablet Formulation (240 mg) | Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 in fasted state. Frel for AUC (0-t) was calculated as Geometric mean of AUC(0-t) of MR Fasted formulation (test) / Geometric mean of AUC(0-t) of Fasted of IR Formulation (reference) multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours |
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| Primary | Part A: Frelformulation Based on AUC(0-24) of GSK2982772 for MR Coated Tablet Formulation (240 mg) | Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 in fasted state. Frel for AUC(0-24) was calculated as Geometric mean of AUC(0-24) of MR Fasted formulation (test) / Geometric mean of AUC(0-24) of Fasted of IR Formulation (reference) multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours |
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| Primary | Part A: Frelformulation Based on Cmax of GSK2982772 for MR Coated Tablet Formulation (240 mg) | Blood samples were collected at indicated time points for analysis of Frelformulation based on Cmax of GSK2982772 in fasted state. Frel for Cmax was calculated as Geometric mean of Cmax of MR Fasted formulation (test) / Geometric mean of Cmax of Fasted Formulation of IR formulation (reference) multiplied by 100. | PK Population. | Posted | Number | 90% Confidence Interval | Percentage bioavailability | Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 36 and 48 hours |
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| Secondary | Part A: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a clinical study participants, 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 may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events that may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before. | Safety Population consisted of all participants who receive at least 1 dose of study treatment. | Posted | Count of Participants | Participants | Up to Day 67 |
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| Secondary | Part A: Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance (PCI) Criteria | Clinical chemistry parameters with PCI values:albumin (low: <30 millimoles per liter[mmol/L]), Alanine transaminase (ALT) (high: >=2xupper limit of normal [ULN]), Aspartate Aminotransferase(AST) (high: >=2xULN), Alkaline phosphatase(ALP) (high:>=2xULN), calcium(low: <2 mmol/L, high: >2.75 mmol/L),creatinine (high: >44.2 mmol/L),glucose (low: <3 mmol/L,high: >9 mmol/L), potassium (low: <3 mmol/L,high: >5.5 mmol/L),sodium (low: <130 mmol/L,high: >150 mmol/L),total bilirubin(high :>= 1.5xULN). Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High),or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the participants has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Data for worst-case post-Baseline has been reported. | Safety Population. | Posted | Count of Participants | Participants | Up to Day 67 |
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| Secondary | Part A: Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria | Hematology parameters with PCI ranges: hematocrit (high: >0.54 percentage of red blood cells), hemoglobin (high: >180 grams per liter [g/L]), lymphocytes (low: <0.8*giga cells per liter [10^9/L]), total neutrophil count (low: <1.5*10^9/L), platelet count (low: <100*10^9/L and high: >550*10^9/L), and while blood cell (WBC) count (low: <3*10^9/L and high: >20*10^9/L). Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Data for worst-case post-Baseline has been reported. | Safety Population. | Posted | Count of Participants | Participants | Up to Day 67 |
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| Secondary | Part A: Number of Participants With Abnormal Urinalysis Dipstick Results | Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination was performed abnormal data for red blood cells (RBC): 1-9 High potential field (HPF) and WBC: 1-9/ HPF; WBC: 10-50/HPF has been presented. | Safety Population. | Posted | Count of Participants | Participants | Day 2 (post-dose) |
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| Secondary | Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in IR Formulation | SBP and DBP were measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Safety Population. | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours |
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| Secondary | Part A: Change From Baseline in SBP and DBP in MR Formulation | SBP and DBP were measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Safety Population. | Posted | Mean | Standard Deviation | Millimeters of mercury | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours |
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| Secondary | Part A: Change From Baseline in Heart Rate in IR Formulation | Heart rate was measured in a semi-supine position after 5 minutes of rest of participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Safety Population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours |
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| Secondary | Part A: Change From Baseline in Heart Rate in MR Formulation | Heart rate was measured in a semi-supine position after 5 minutes of rest of participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Safety Population. | Posted | Mean | Standard Deviation | Beats per minute | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours |
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| Secondary | Part A: Change From Baseline in Respiration Rate in IR Formulation | Respiratory rate was measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Safety Population. | Posted | Mean | Standard Deviation | Breaths per minute | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours |
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| Secondary | Part A: Change From Baseline in Respiration Rate in MR Formulation | Respiratory rate was measured in a semi-supine position after 5 minutes of rest of the participant. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles). | Posted | Mean | Standard Deviation | Breaths per minute | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours |
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| Secondary | Part A: Change From Baseline in Body Temperature in IR Formulation | Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Safety Population. | Posted | Mean | Standard Deviation | Degrees Celsius | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours |
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| Secondary | Part A: Change From Baseline in Body Temperature in MR Formulation | Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value. | Safety Population. | Posted | Mean | Standard Deviation | Degrees Celsius | Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24 hours, Day 3: 48 hours |
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| Secondary | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in IR Formulation | Single 12-lead ECGs were obtained using an automated ECG machine that calculated PR, QRS, QT and Corrected QT (QTc) intervals. ECG measurements were performed in a semi-supine or supine position. Number of participants with abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst-case post-Baseline has been reported. | Safety Population. | Posted | Count of Participants | Participants | Up to Day 67 |
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| Secondary | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in MR Formulation | Single 12-lead ECGs were obtained using an automated ECG machine that calculated PR, QRS, QT and Corrected QT (QTc) intervals. ECG measurements were performed in a semi-supine or supine position. Number of participants with abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for worst-case post-Baseline has been reported. | Safety Population. | Posted | Count of Participants | Participants | Up to Day 67 |
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| 0 |
| 16 |
| 0 |
| 16 |
| 2 |
| 16 |
| EG001 | Part A: MR-12h 240 mg Fasted | Participants received a single oral dose of 240 mg GSK2982772 MR-12h tablet in fasted state | 0 | 16 | 0 | 16 | 5 | 16 |
| EG002 | Part A: MR-18h 240mg Fasted | Participants received a single oral dose of 240 mg GSK2982772 MR-18h tablet in fasted state | 0 | 16 | 0 | 16 | 3 | 16 |
| EG003 | Part A: MR-12h 240mg Fed (High-Fat) | Participants received a single oral dose of 240 mg GSK2982772 MR-12h tablet after a high fat meal in fed state | 0 | 12 | 0 | 12 | 3 | 12 |
| EG004 | Part A: MR-18h 240mg Fed (High-Fat) | Participants received a single oral dose of 240 mg GSK2982772 MR-18h tablet after high fat meal in fed state | 0 | 16 | 0 | 16 | 3 | 16 |
| EG005 | Part A: MR-16h 240mg Fasted | Participants received a single oral dose of 240 mg GSK2982772 MR-16h tablet in fasted state | 0 | 12 | 0 | 12 | 4 | 12 |
| EG006 | Part B: MR-16h 480mg Fasted | Participants received a single oral dose of 480 mg GSK2982772 MR-16 h (80% release in 16 hours) tablet in fasted state | 0 | 16 | 0 | 16 | 8 | 16 |
| EG007 | Part B: MR-16h 480 mg Fed (Std) | Participants received a single oral dose of 480 mg GSK2982772 MR-16h (80% release in 16 hours) tablet after a standard breakfast (fed state) | 0 | 14 | 0 | 14 | 4 | 14 |
| EG008 | Part B: MR-16h 480mg Fed (High-fat) | Participants received a single oral dose of 480 mg GSK2982772 MR-16h (80% release in 16 hours) tablet after high fat breakfast (fed state) | 0 | 15 | 0 | 15 | 1 | 15 |
| EG009 | Part B: MR-16h 480mg Fed (High-Fat) (Enteric Coated) | Participants received a single oral dose of 480 mg GSK2982772 MR-16h (80% release in 16 hours) enteric coated tablet after a high fat breakfast (fed state) | 0 | 14 | 0 | 14 | 3 | 14 |
| EG010 | Part B: MR-16h 960mg Fasted | Participants received a single oral dose of 960 mg GSK2982772 MR-16h (80% release in 16 hours) tablet in fasted state | 0 | 15 | 0 | 15 | 3 | 15 |
| EG011 | Part B: MR-16h 120mg Fasted | Participants received 120 mg GSK2982772 MR-16 h (80% release in 16 hours) tablet in fasted state | 0 | 15 | 0 | 15 | 3 | 15 |
| Gastroenteritis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Abdominal pain lower | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Application site irritation | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Chest discomfort | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Transaminases increased | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 22.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Haematoma | Vascular disorders | MedDRA 22.0 | Systematic Assessment |
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| Oral herpes | Infections and infestations | MedDRA 22.0 | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Tooth loss | Gastrointestinal disorders | MedDRA 22.0 | Systematic Assessment |
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| Catheter site swelling | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Peripheral swelling | General disorders | MedDRA 22.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Soft tissue injury | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Tooth fracture | Injury, poisoning and procedural complications | MedDRA 22.0 | Systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Depressed mood | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
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| Nightmare | Psychiatric disorders | MedDRA 22.0 | Systematic Assessment |
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| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA 22.0 | Systematic Assessment |
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| Cardiac murmur | Investigations | MedDRA 22.0 | Systematic Assessment |
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| Conjunctival haemorrhage | Eye disorders | MedDRA 22.0 | 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
| Any SAEs |
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| ALT, To High |
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| AST, To Normal or No Change |
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| AST, To High |
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| ALP, To Normal or No Change |
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| ALP, To High |
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| Albumin, To low |
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| Albumin, To Normal or no Change |
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| Calcium, To low |
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| Calcium, To Normal or No Change |
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| Calcium, To High |
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| Creatinine, To Normal or No Change |
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| Creatinine, To High |
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| Glucose, To low |
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| Glucose, To Normal or No Change |
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| Glucose, To High |
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| Potassium, To low |
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| Potassium, To Normal or No Change |
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| Potassium, To High |
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| Sodium, To low |
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| Sodium, To Normal or No Change |
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| Sodium, To High |
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| Total Bilirubin, To Normal or No Change |
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| Total Bilirubin, To High |
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| Hematocrit, To High |
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| Hemoglobin, To Normal or No Change |
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| Hemoglobin, To High |
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| Lymphocytes, To Low |
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| Lymphocytes, To Normal or No Change |
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| Platelet count, To Low |
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| Platelet count, To Normal or No change |
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| Platelet count, To High |
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| Total neutrophils, To Low |
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| Total Neutrophils, To Normal or No Change |
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| WBC count, To Low |
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| WBC count, To Normal or no Change |
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| WBC count, To High |
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| WBC 1-9/HPF |
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| WBC 10-50/HPF |
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| Title | Measurements |
|---|---|
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| DBP, Day1, 2 hours |
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| DBP, Day 1, 12 hours |
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| DBP, Day 2, 24 hours |
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| SBP, Day1, 12 hours |
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| SBP, Day 2, 24 hours |
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| SBP, Day3, 48 hours, |
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| DBP, Day1, 2 hours |
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| DBP, Day1, 12 hours |
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| DBP, Day2, 24 hours |
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| DBP, Day3, 48 hours |
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| Title | Measurements |
|---|---|
|
| Day 1, 12 hours |
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| Day 2, 24 hours |
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| Day 3, 48 hours |
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| Title | Measurements |
|---|---|
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| Day 1, 12 hours; n=15, 16, 12, 16, 12 |
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| Day 2, 24 hours; n=16, 16, 12, 16, 12 |
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| Day 3, 48 hours; n=16, 16, 12, 16, 12 |
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| Title | Measurements |
|---|---|
|
| Day 1, 12 hours |
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| Day 2, 24 hours |
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| Day 3, 48 hours |
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| Abnormal - Clinically Significant |
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