Inflammatory Bowel DiseasesPhase 1NCT03358407

GSK2983559 First Time in Human Study

A Phase 1 study testing GSK2983559 in people with Inflammatory Bowel Diseases, run by GlaxoSmithKline at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Inflammatory Bowel Diseases
What is being tested?: GSK2983559
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 31 participants
Where: 1 siteUnited Kingdom
Study dates: 11 Jan 2018to 19 Feb 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Male and female subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Volunteers who are overtly healthy as determined by medical evaluation including medical and psychiatric history, physical examination, neurological examination, clinical laboratory tests and cardiac monitoring.
3Body weight >= 50 kg (kilogram) and body mass index (BMI) within the range 19-32 kilogram per meter square (kg/m^2) .
A male subject must agree to use a highly effective contraception during the treatment period and for at least 5 half-lives plus an additional 90 days after the last dose of study treatment and refrain from donating sperm during this period.
A female subject is eligible to participate if she is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP)
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Participants must agree to avoid prolonged Ultraviolet (UV) exposure to natural sunlight without required Ultraviolet A (UVA)/ Ultraviolet B (UVB) protection or tanning beds for the duration of the study.

Who cannot join

History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
History of clinically significant psychiatric disorders as judged by the investigator.
Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a subject's lifetime.
ALT >1.5x upper limit of normal (ULN).
Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

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Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
History of Gastrointestinal (GI) surgery (with exception of appendectomy)
Average QTc > 450 millisecond (msec)
Intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing
Live or attenuated vaccine(s) within 30 days of randomization, or plans to receive such vaccines during the study or plans to receive a vaccine within 30 days + 5 half-lives of the last dose of study medication.
Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Current use or history of regular tobacco- or nicotine-containing products within 6 months prior to screening. Subject must have urinary cotinine levels indicative of non-smoking status at screening visit.
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Current enrollment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
Subjects with impaired renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation <= 60 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) estimated by the CKD-EPI equation.
An elevated C-reactive protein (CRP) outside of the normal reference range.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded. Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
A positive pre-study drug/alcohol screen.
A positive test for HIV antibody.
A positive diagnostic TB test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test. In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative. In cases where the QuantiFERON or T-spot test is positive, but a locally-read follow up chest x-ray, shows no evidence of current or previous pulmonary tuberculosis, the subject may be eligible for the study at the discretion of the Investigator and GSK Medical Monitor.
Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates participation in the study.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
Part A (Food Effect) Cohort: Subject must have no dietary restrictions (e.g., lactose intolerance) or inability to eat a high fat meal.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, Cambridgeshire, CB2 2GG

Other trials in United Kingdom

About this study

Official title: A Single-centre, Randomized, Double-blind (Sponsor Open), Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2983559, in Single (in Both Fed and Fasted States) and Repeat Oral Doses in Healthy Participants

This study is the first administration of GSK2983559, a selective receptor interacting protein 2 (RIP2) kinase inhibitor, to humans. This will be randomized, double-blinded (sponsor open) and two part study (A and B). Part A of the study is single ascending dose crossover design with two separate cohorts (1 and 2). In Part A, 9 single dose levels will be explored. In Cohort 1, 10 healthy subjects will randomized to receive single oral doses of either GSK2983559 or placebo in a ratio of 4:1 in 5 way cross-over design with 5 treatment periods. In Cohort 2, 8 healthy subjects will be randomized to receive single oral doses of either GSK2983559 or placebo in a ratio of 3:1 in 4 way cross-overs design with 4 treatment periods. In Cohort 2 there will be an additional period (period 5-open label) for assessing GSK2983559 under fed conditions. There will be 48 hours wash-out period between each dose escalation period. Part B is repeat ascending dose sequential group design. It will contain 4 Cohorts of and dosing will be done sequential dosing. Subjects in Part B will receive once daily (QD) dose or twice daily dose (will be decided based upon the pharmacokinetic, safety and tolerability observed in Part A). There will 58 subjects involved in this study. Total duration of Part A will be approximately for 11 Weeks and Part B will be approximately for 15 Weeks.

Conditions: Inflammatory Bowel Diseases
Being tested: GSK2983559, Placebo
Keywords: Inflammatory Bowel disease, Pro-drug, Double-blinded, Crossover
Medical subject headings: Inflammatory Bowel Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK2983559Drug
GSK2983559 will be available as oral capsules with dose strength of 2-45 milligram (mg), 100 and 114 mg.
PlaceboDrug
Placebo oral capsules matching GSK2983559 will be available for subjects.

Study groups in NCT03358407
Study group	Role	What they receive
Part A: Cohort 1	Experimental	Cohort 1 will be 5-way crossover with 5 treatment periods. Subjects will be randomized in the ratio 4:1 to receive either single dose of GSK2983559 or placebo. Receives: Drug: GSK2983559; Drug: Placebo
Part A: Cohort 2 fasting	Experimental	Cohort 2 will be 4-way crossover design with one additional period of open-label. Subjects will be randomized in the ratio 3:1 to receive either single dose of GSK2983559 or placebo in fasted conditions Receives: Drug: GSK2983559; Drug: Placebo
Part A: Cohort 2 fed	Experimental	In Cohort 2, treatment period 5 will be open-label period. This open-label period is to determine food effect and subjects will receive GSK2983559 under fed conditions. Receives: Drug: GSK2983559
Part B	Experimental	Part B is repeat ascending dose sequential period. There will four cohorts (3-6) of 10 healthy subjects. In each cohort subjects will be randomized to receive GSK2983559 or placebo in ratio 4:1. Subjects will receive GSK2983559 or placebo QD and twice daily dose will be decided based upon the pharmacokinetic, safety and tolerability observed in Part A. Receives: Drug: GSK2983559; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Number of Participants With Non Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
An adverse event was 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. SAE was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement.
Measured: Up to 7 weeks
Part B: Number of Participants With Non-SAEs and SAEs
An adverse event was 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. SAE was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-SAEs and SAEs were planned to be collected.
Measured: Up to 11 weeks
Part A: Number of Participants With Worst Case Hematology Parameters of Potential Clinical Importance (PCI)
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and white blood cells (WBCs) count. PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from baseline<0.0075); hemoglobin (high: >180 grams per liter [g/L] and low: change from baseline<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Only those hematology parameters with PCI values have been presented.
Measured: Up to 7 weeks
Part B: Number of Participants With Worst Case Hematology Parameters of PCI
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and WBC count. PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from baseline<0.0075); hemoglobin (high: >180 grams per liter [g/L] and low: change from baseline<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants with worst case hematology parameters of PCI were planned to be collected.
Measured: Up to 11 weeks
Part A: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI
Clinical chemistry parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin (T.bil). PCI ranges were: ALT, AST, ALP (high): >=2*Upper limit of Normal(ULN) units per liter(U/L), albumin(low): 30 g/L, calcium: <2(low) or >2.75 millimoles per liter (mmol/L)(high), creatinine (high): increase from Baseline >44.2 micromoles per liter(µmol/L), glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and T.bil(high): >=1.5*ULN (µmol/L). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Measured: Up to 7 weeks
Part B: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI
Clinical chemistry parameters included ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were ALT(high): >=2*ULN U/L, albumin(low): 30 g/L, alkaline phosphatase(high): >=2*ULN U/L, AST(high): >=2*ULN U/L, calcium: <2(low) or >2.75 mmol/L (high), creatinine (high): increase from Baseline >44.25 µmol/L, glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and total bilirubin(high): >=1.5*ULN (µmol/L). Participants with worst case clinical chemistry parameters of PCI were planned to be collected.
Measured: Up to 11 weeks
Part A: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Baseline was defined as latest predose (Day 1) assessment with a non-missing value.
Measured: Up to 7 weeks
Part B: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Urine analysis included assessment of glucose, ketones, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner. Baseline was defined as latest predose (Day 1) assessment with a non-missing value. Participants with worst case any increase in urinalysis results post-Baseline relative to Baseline were planned to be collected.
Measured: Up to 11 weeks
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
12-lead ECGs were obtained using an ECG machine. Only those participants who had any abnormal ECG findings are presented. Abnormal ECG findings were categorized as clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings. 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.
Measured: 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24 and 48 hours post-dose
Part B: Number of Participants With Abnormal ECG Findings
12-lead ECGs were planned to be obtained using an ECG machine. Abnormal ECG findings were categorized as CS and NCS abnormal ECG findings. CS 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. Participants with any abnormal ECG findings were planned to be evaluated.
Measured: Up to 11 weeks
Part A: Number of Participants With Worst Case Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Values of PCI
DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: <45 millimeters of mercury (mmHg) (lower) and >100 mmHg (higher) and SBP: <85 mmHg (lower) and >160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Measured: Up to 7 weeks
Part B: Number of Participants With Worst Case DBP and SBP Values of PCI
DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: <45 mmHg (lower) and >100 mmHg (higher) and SBP: <85 mmHg (lower) and >160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category. Participants with worst case DBP and SBP values of PCI were planned to be evaluated.
Measured: Up to 11 weeks
Part A: Number of Participants With Worst Case Respiration Rate Values of PCI
Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <=8 breaths per minute (lower) and >=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Measured: Up to 7 weeks
Part B: Number of Participants With Worst Case Respiration Rate Values of PCI
Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <=8 breaths per minute (lower) and >=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category. Participants with worst case respiratory rate values of PCI were planned to be evaluated.
Measured: Up to 11 weeks
Part A: Number of Participants With Worst Case Heart Rate Values of PCI
Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <40 beats per minute (lower) and >110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Measured: Up to 7 weeks
Part B: Number of Participants With Worst Case Heart Rate Values of PCI
Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <40 beats per minute (lower) and >110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category. Participants with worst case heart rate values of PCI were planned to be evaluated.
Measured: Up to 11 weeks
Part A: Number of Participants With Worst Case Body Temperature Values of PCI
Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included <=35.5 degrees Celsius (lower) and >=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Measured: Up to 7 weeks
Part B: Number of Participants With Worst Case Body Temperature Values of PCI
Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included <=35.5 degrees Celsius (lower) and >=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category. Participants with worst case body temperature values of PCI were planned to be evaluated.
Measured: Up to 11 weeks
Part A: Number of Participants With Abnormal Findings in Physical Examination
Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. This analysis was not planned and data was not collected and not captured in the database.
Measured: Up to 7 weeks
Part B: Number of Participants With Abnormal Findings in Physical Examination
Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. Data was not collected and not captured in the database.
Measured: Up to 11 weeks
Part A: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points
Blood samples were collected to evaluate activated partial thromboplastin time (APTT) and prothrombin time (PT) at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline (Day 1, Pre-dose), 24 and 48 hours post-dose
Part B: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points
Blood samples were planned to be collected to evaluate PTT and PT at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline and Up to 11 weeks
Part A: Change From Baseline in International Normalized Ratio at Indicated Time Points
Blood samples were collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline (Day 1, Pre-dose), 24 and 48 hours
Part B: Change From Baseline in International Normalized Ratio at Indicated Time Points
Blood samples were planned to be collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline and Up to 11 weeks

Secondary outcomes (62)

Part A (Cohort 1): Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2983559
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-t) for GSK2983559
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC From Time Zero to Infinity (AUC[0-inf]) for GSK2983559
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-inf) for GSK2983559
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Maximum Plasma Concentration (Cmax) for GSK2983559
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Cmax for GSK2983559
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Cmax for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Terminal Elimination Half-life (T1/2) for GSK2983559
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): T1/2 for GSK2983559
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): T1/2 for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Time to Cmax (Tmax) for GSK2983559
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Tmax for GSK2983559
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Tmax for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559)
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-t) for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-t) for GSK2983559 on Day 14
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC From 0 Hours to the Time of Next Dosing AUC(0-tau) for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-tau) for GSK2983559 on Day 14
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Cmax for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure Cmax at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Cmax for GSK2983559 on Day 14
Blood samples were planned to be collected to measure Cmax at indicated time-points.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure Cmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure Cmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Tmax for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure Tmax at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Tmax for GSK2983559 on Day 14
Blood samples were planned to be collected to measure Tmax at indicated time-points.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure Tmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure Tmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: T1/2 for GSK2983559 Following Single Dose on Day 1
Blood samples were planned to be collected to measure T1/2 at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: T1/2 for GSK2983559 on Day 14
Blood samples were planned to be collected to measure T1/2 at indicated time-points.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Blood samples were planned to be collected to measure T1/2 at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Blood samples were planned to be collected to measure T1/2 at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Accumulation Ratio of GSK2983559
Blood samples were planned to be collected to measure accumulation ratio at indicated time-points. Accumulation ratio was to be calculated as ratio of AUC(0-tau) at Day 14 to AUC(0-tau) at Day 1.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Accumulation Ratio of GSK2668176 (Active Moiety of GSK2983559)
Blood samples were planned to be collected to measure accumulation ratio at indicated time-points. Accumulation ratio was to be calculated as ratio of AUC(0-tau) at Day 14 to AUC(0-tau) at Day 1. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC (0-t) for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure AUC(0-t) in fasted condition (Period 4) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): AUC(0-t) for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure AUC(0-t) in fed condition (Period 5) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure AUC(0-t) in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure AUC(0-t) in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): AUC(0-inf) for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure AUC(0-inf) in fasted condition (Period 4) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): AUC(0-inf) for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure AUC(0-inf) in fed condition (Period 5) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure AUC(0-inf) in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure AUC(0-inf) in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): Cmax for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure Cmax in fasted condition (Period 4) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): Cmax for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure Cmax in fed condition (Period 5) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure Cmax in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure Cmax in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): Tmax for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure Tmax in fasted condition (Period 4) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): Tmax for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure Tmax in fed condition (Period 5) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure Tmax in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure Tmax in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): T1/2 for GSK2983559 in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure T1/2 in fasted condition (Period 4) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): T1/2 for GSK2983559 in Fed Condition (Period 5)
Blood samples were planned to be collected to measure T1/2 in fed condition (Period 5) at indicated time-points.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Blood samples were planned to be collected to measure T1/2 in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Blood samples were planned to be collected to measure T1/2 in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Measured: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

11 Jan 201819 Feb 2019

First posted30 Nov 2017
Study start11 Jan 2018
Primary completion19 Feb 2019
Study completion19 Feb 2019

Why it stopped: Terminated due to non clinical toxicology findings and reduced safety margins.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Inflammatory Bowel DiseasesStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03358407
Sponsor's protocol ID: 205021
Other IDs: 2017-002664-40, 2017
Status last verified: Nov 2020
First submitted: 27 Nov 2017
Last updated: 27 Nov 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study is available via the Clinical Study Data Request site.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single-centre, Randomized, Double-blind (Sponsor Open), Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2983559, in Single (in Both Fed and Fasted States) and Repeat Oral Doses in Healthy Participants
ClinicalTrials.gov ID: NCT03358407
Acronym / sponsor ID: 205021
Conditions: Inflammatory Bowel Diseases
Keywords: Inflammatory Bowel disease, Pro-drug, Double-blinded, Crossover
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Terminated due to non clinical toxicology findings and reduced safety margins.
Enrolment: 31 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 11 Jan 2018 (actual)
Primary completion: 19 Feb 2019 (actual)
Study completion: 19 Feb 2019 (actual)
First posted: 30 Nov 2017 (actual)
Results: Posted 22 Jun 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
Part A: Cohort 1	Experimental	Drug: GSK2983559, Drug: PlaceboCohort 1 will be 5-way crossover with 5 treatment periods. Subjects will be randomized in the ratio 4:1 to receive either single dose of GSK2983559 or placebo.
Part A: Cohort 2 fasting	Experimental	Drug: GSK2983559, Drug: PlaceboCohort 2 will be 4-way crossover design with one additional period of open-label. Subjects will be randomized in the ratio 3:1 to receive either single dose of GSK2983559 or placebo in fasted conditions
Part A: Cohort 2 fed	Experimental	Drug: GSK2983559In Cohort 2, treatment period 5 will be open-label period. This open-label period is to determine food effect and subjects will receive GSK2983559 under fed conditions.
Part B	Experimental	Drug: GSK2983559, Drug: PlaceboPart B is repeat ascending dose sequential period. There will four cohorts (3-6) of 10 healthy subjects. In each cohort subjects will be randomized to receive GSK2983559 or placebo in ratio 4:1. Subjects will receive GSK2983559 or placebo QD and twice daily dose will be decided based upon the pharmacokinetic, safety and tolerability observed in Part A.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Male and female subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Volunteers who are overtly healthy as determined by medical evaluation including medical and psychiatric history, physical examination, neurological examination, clinical laboratory tests and cardiac monitoring.
3Body weight >= 50 kg (kilogram) and body mass index (BMI) within the range 19-32 kilogram per meter square (kg/m^2) .
A male subject must agree to use a highly effective contraception during the treatment period and for at least 5 half-lives plus an additional 90 days after the last dose of study treatment and refrain from donating sperm during this period.
A female subject is eligible to participate if she is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP)

Key exclusion criteria (24 listed)

History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
History of clinically significant psychiatric disorders as judged by the investigator.
Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a subject's lifetime.
ALT >1.5x upper limit of normal (ULN).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK2983559GSK2983559 will be available as oral capsules with dose strength of 2-45 milligram (mg), 100 and 114 mg.	Drug	Part A: Cohort 1, Part A: Cohort 2 fasting, Part A: Cohort 2 fed, Part B
PlaceboPlacebo oral capsules matching GSK2983559 will be available for subjects.	Drug	Part A: Cohort 1, Part A: Cohort 2 fasting, Part B

Primary outcome

Part A: Number of Participants With Non Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Time frame: Up to 7 weeks
An adverse event was 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. SAE was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement.
Part B: Number of Participants With Non-SAEs and SAEs
Time frame: Up to 11 weeks
An adverse event was 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. SAE was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-SAEs and SAEs were planned to be collected.
Part A: Number of Participants With Worst Case Hematology Parameters of Potential Clinical Importance (PCI)
Time frame: Up to 7 weeks
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and white blood cells (WBCs) count. PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from baseline<0.0075); hemoglobin (high: >180 grams per liter [g/L] and low: change from baseline<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Only those hematology parameters with PCI values have been presented.
Part B: Number of Participants With Worst Case Hematology Parameters of PCI
Time frame: Up to 11 weeks
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and WBC count. PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from baseline<0.0075); hemoglobin (high: >180 grams per liter [g/L] and low: change from baseline<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'To within Range or No Change' category. Participants with worst case hematology parameters of PCI were planned to be collected.
Part A: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI
Time frame: Up to 7 weeks
Clinical chemistry parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin (T.bil). PCI ranges were: ALT, AST, ALP (high): >=2*Upper limit of Normal(ULN) units per liter(U/L), albumin(low): 30 g/L, calcium: <2(low) or >2.75 millimoles per liter (mmol/L)(high), creatinine (high): increase from Baseline >44.2 micromoles per liter(µmol/L), glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and T.bil(high): >=1.5*ULN (µmol/L). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Part B: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI
Time frame: Up to 11 weeks
Clinical chemistry parameters included ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were ALT(high): >=2*ULN U/L, albumin(low): 30 g/L, alkaline phosphatase(high): >=2*ULN U/L, AST(high): >=2*ULN U/L, calcium: <2(low) or >2.75 mmol/L (high), creatinine (high): increase from Baseline >44.25 µmol/L, glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and total bilirubin(high): >=1.5*ULN (µmol/L). Participants with worst case clinical chemistry parameters of PCI were planned to be collected.
Part A: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Time frame: Up to 7 weeks
Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Baseline was defined as latest predose (Day 1) assessment with a non-missing value.
Part B: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Time frame: Up to 11 weeks
Urine analysis included assessment of glucose, ketones, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner. Baseline was defined as latest predose (Day 1) assessment with a non-missing value. Participants with worst case any increase in urinalysis results post-Baseline relative to Baseline were planned to be collected.
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: 1.5, 2, 2.5, 3, 4, 5, 8, 12, 24 and 48 hours post-dose
12-lead ECGs were obtained using an ECG machine. Only those participants who had any abnormal ECG findings are presented. Abnormal ECG findings were categorized as clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings. 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.
Part B: Number of Participants With Abnormal ECG Findings
Time frame: Up to 11 weeks
12-lead ECGs were planned to be obtained using an ECG machine. Abnormal ECG findings were categorized as CS and NCS abnormal ECG findings. CS 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. Participants with any abnormal ECG findings were planned to be evaluated.
Part A: Number of Participants With Worst Case Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Values of PCI
Time frame: Up to 7 weeks
DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: <45 millimeters of mercury (mmHg) (lower) and >100 mmHg (higher) and SBP: <85 mmHg (lower) and >160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Part B: Number of Participants With Worst Case DBP and SBP Values of PCI
Time frame: Up to 11 weeks
DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: <45 mmHg (lower) and >100 mmHg (higher) and SBP: <85 mmHg (lower) and >160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category. Participants with worst case DBP and SBP values of PCI were planned to be evaluated.
Part A: Number of Participants With Worst Case Respiration Rate Values of PCI
Time frame: Up to 7 weeks
Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <=8 breaths per minute (lower) and >=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Part B: Number of Participants With Worst Case Respiration Rate Values of PCI
Time frame: Up to 11 weeks
Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <=8 breaths per minute (lower) and >=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category. Participants with worst case respiratory rate values of PCI were planned to be evaluated.
Part A: Number of Participants With Worst Case Heart Rate Values of PCI
Time frame: Up to 7 weeks
Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <40 beats per minute (lower) and >110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Part B: Number of Participants With Worst Case Heart Rate Values of PCI
Time frame: Up to 11 weeks
Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <40 beats per minute (lower) and >110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category. Participants with worst case heart rate values of PCI were planned to be evaluated.
Part A: Number of Participants With Worst Case Body Temperature Values of PCI
Time frame: Up to 7 weeks
Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included <=35.5 degrees Celsius (lower) and >=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category.
Part B: Number of Participants With Worst Case Body Temperature Values of PCI
Time frame: Up to 11 weeks
Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included <=35.5 degrees Celsius (lower) and >=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, 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 within range, were recorded in the 'To within Range or No Change' category. Participants with worst case body temperature values of PCI were planned to be evaluated.
Part A: Number of Participants With Abnormal Findings in Physical Examination
Time frame: Up to 7 weeks
Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. This analysis was not planned and data was not collected and not captured in the database.
Part B: Number of Participants With Abnormal Findings in Physical Examination
Time frame: Up to 11 weeks
Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. Data was not collected and not captured in the database.
Part A: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points
Time frame: Baseline (Day 1, Pre-dose), 24 and 48 hours post-dose
Blood samples were collected to evaluate activated partial thromboplastin time (APTT) and prothrombin time (PT) at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Part B: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points
Time frame: Baseline and Up to 11 weeks
Blood samples were planned to be collected to evaluate PTT and PT at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Part A: Change From Baseline in International Normalized Ratio at Indicated Time Points
Time frame: Baseline (Day 1, Pre-dose), 24 and 48 hours
Blood samples were collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Part B: Change From Baseline in International Normalized Ratio at Indicated Time Points
Time frame: Baseline and Up to 11 weeks
Blood samples were planned to be collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

62 secondary outcomes

Part A (Cohort 1): Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-t) for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC From Time Zero to Infinity (AUC[0-inf]) for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-inf) for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Maximum Plasma Concentration (Cmax) for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Cmax for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Cmax for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Terminal Elimination Half-life (T1/2) for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): T1/2 for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): T1/2 for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Time to Cmax (Tmax) for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Tmax for GSK2983559
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 1): Tmax for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559)
Time frame: Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-t) for GSK2983559 Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-t) for GSK2983559 on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC From 0 Hours to the Time of Next Dosing AUC(0-tau) for GSK2983559 Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-tau) for GSK2983559 on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Cmax for GSK2983559 Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Cmax for GSK2983559 on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Tmax for GSK2983559 Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Tmax for GSK2983559 on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: T1/2 for GSK2983559 Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: T1/2 for GSK2983559 on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period
Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period
Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Time frame: Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Results and safety

Results posted to the registry on 22 Jun 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A-Cohort 1: Placebo/GSK 4mg/GSK 10mg/GSK 30mg/GSK 100mg	2	2
Part A-Cohort 1: GSK 2mg/Placebo/GSK 10mg/GSK 30mg/GSK 100mg	2	2
Part A-Cohort 1: GSK 2mg/GSK 4mg/Placebo/GSK 30mg/GSK 100mg	2	2
Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/Placebo/GSK 100mg	2	2
Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/GSK 30mg/Placebo	2	2
Part A-Cohort 2: Placebo/GSK 400mg	0	0
Part A-Cohort 2: GSK 200mg/Placebo	0	0
Part A-Cohort 2: GSK 200mg/GSK 400mg	0	0
Part B: Placebo	0	0
Part B: GSK2983559	0	0

Primary outcome: Part A: Number of Participants With Non Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)

Time frame: Up to 7 weeks. Count of participants. Unit: Participants

Measure	Part A: Placebo n = 16	Part A-Cohort 1: GSK2983559 2 mg n = 8	Part A-Cohort 1: GSK2983559 4 mg n = 8	Part A-Cohort 1: GSK2983559 10 mg n = 8	Part A-Cohort 1: GSK2983559 30 mg n = 8	Part A-Cohort 1: GSK2983559 100 mg n = 8	Part A-Cohort 2: GSK2983559 200 mg n = 9	Part A-Cohort 2: GSK2983559 400 mg n = 9
Non-SAEs	6	2	2	1	1	2	4	4
SAEs	0	0	0	0	0	0	0	0

Population analysed: Safety Population comprised of all randomized participants who received at least one dose of study treatment. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Primary outcome: Part B: Number of Participants With Non-SAEs and SAEs

Time frame: Up to 11 weeks

Population analysed: Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Primary outcome: Part A: Number of Participants With Worst Case Hematology Parameters of Potential Clinical Importance (PCI)

Time frame: Up to 7 weeks. Count of participants. Unit: Participants

Measure	Part A: Placebo n = 16	Part A-Cohort 1: GSK2983559 2 mg n = 8	Part A-Cohort 1: GSK2983559 4 mg n = 8	Part A-Cohort 1: GSK2983559 10 mg n = 8	Part A-Cohort 1: GSK2983559 30 mg n = 8	Part A-Cohort 1: GSK2983559 100 mg n = 8	Part A-Cohort 2: GSK2983559 200 mg n = 9	Part A-Cohort 2: GSK2983559 400 mg n = 9
Hematocrit, To low	0	0	0	0	0	0	0	0
Hematocrit, To within range or no change	16	8	8	8	8	8	9	9
Hematocrit, To high	0	0	0	0	0	0	0	0
Hemoglobin, To low	0	0	0	0	0	0	0	0
Hemoglobin, To within range or no change	16	8	8	8	8	8	9	9
Hemoglobin, To high	0	0	0	0	0	0	0	0
Lymphocytes, To low	1	0	0	0	0	0	0	0
Lymphocytes, To within range or no change	15	8	8	8	8	8	9	9

Population analysed: Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Primary outcome: Part B: Number of Participants With Worst Case Hematology Parameters of PCI

Time frame: Up to 11 weeks

Population analysed: Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

62 secondary outcomes are reported in the full results.

Adverse events

Time frame: Non-SAEs and SAEs were reported from start of study treatment (Day 1) up to Week 7 for Part A. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Placebo	0 of 16 (0%)	6 of 16 (37.5%)	0 of 16
Part A-Cohort 1: GSK2983559 2 mg	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Part A-Cohort 1: GSK2983559 4 mg	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Part A-Cohort 1: GSK2983559 10 mg	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
Part A-Cohort 1: GSK2983559 30 mg	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
Part A-Cohort 1: GSK2983559 100 mg	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Part A-Cohort 2: GSK2983559 200 mg	0 of 9 (0%)	4 of 9 (44.4%)	0 of 9
Part A-Cohort 2: GSK2983559 400 mg	0 of 9 (0%)	4 of 9 (44.4%)	0 of 9

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. IPD for this study is available via the Clinical Study Data Request site.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK2983559 in people with Inflammatory Bowel Diseases, run by GlaxoSmithKline at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With Non Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) (time frame: Up to 7 weeks). The study lists 24 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03358407.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.