Clinical trial NCT03266172: A Study to Compare the Pharmacokinetics (PK) of GSK2982772 Following Administration of Different Modified Release (MR) Formulations in Capsule and MR Tablet Formulations Relative to an Immediate Release (IR) Tablet Formulation and to Check the PK of MR Formulation in Capsule Following Repeat Doses
Official title: A Three Part, Non-randomized, Open Label Study Designed to Assess the Pharmacokinetics of GSK2982772 Following Administration of Minitab Modified Release Formulations in a Capsule Relative to an Immediate Release Reference Tablet Formulation (Part A), the Pharmacokinetics of Escalating, Repeat Doses of a Selected Minitab Modified Release Prototype (Part B) , and the Pharmacokinetics of GSK2982772 Following Administration of Modified Release Tablet Formulations in the Fed and Fasted State (Part C) in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Autoimmune Diseases
Keywords: immediate release tablet
GSK2982772
Modified release
minitablet
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Quotient Clinical
First posted: 2017-08-30
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A of the study will be a non-randomized 6 period, sequential, 6-way fixed sequence design. Part B of the study will be a repeat dose study. Part C of the study will be a non-randomized 6 period, sequential, fixed sequence crossover design.
Primary purpose: TREATMENT

Brief summary: GSK2982772 is a first-in-class, highly selective, receptor-interacting protein-1 (RIP1) kinase inhibitor being developed for the treatment of inflammatory bowel disease, plaque psoriasis (PsO), rheumatoid arthritis (RA) and other disease conditions. PK data from the first time in human (FTIH) study for GSK2982772 showed that the half life of GSK2982772 was short (approximately 2 to 3 hours). A once daily (QD) formulation would be more convenient from a subject perspective and could offer the advantage of providing a flatter GSK2982772 concentration time profile. Following completion of Parts A and B, it was determined that the slowest minitab formulation provided a PK profile suitable for QD dosing but this formulation was susceptible to a food effect. This study will evaluate the pharmacokinetics of GSK2982772 following administration of different minitab MR formulations in a capsule relative to an IR reference tablet formulation, the pharmacokinetics of selected MR formulation in capsule following repeat doses for 3 days and to compare the pharmacokinetics of GSK2982772 following administration of MR tablet formulations in the fed and fasted state relative to an IR tablet formulation. The study is divided into three parts: Part A will be a non-randomized 6 periods, sequential, 6-way fixed sequence design in which up to 4 MR minitab formulations in a capsule will be evaluated. Periods 1, 2, and 3 will evaluate a slow MR release duration (nominally 24 hours), a fast MR release duration (nominally 10 hours), and IR tablet respectively. Periods 4, 5 and 6 will have flexible dose regimen and it will depend on the outcomes of Period 1 to 3. Subjects will be admitted to the clinic the previous day before dosing. Each in-patient period will consist of 3 days and 2 nights followed by a minimum washout period of 7 days between doses, for both Part A and C. In Part A and C, 16 healthy subjects will be enrolled such that at least 12 evaluable subjects complete the study. Part B will be an open-label, repeat dose study in which the selected MR minitab formulation in capsule will be evaluated. Each in-patient period will consist of 5 days and 4 nights. There will be a minimum of 7 days washout period between the last morning dose of one period and the first dose of the next period. In Part B, 10 healthy subjects will be enrolled such that at least 6 evaluable subjects complete the study. Part C of the study will be a non-randomised 6 period, sequential, fixed sequence crossover design in which MR tablet formulations will be evaluated. Periods 1 and 2 will evaluate single dose administration of a 240 milligram (mg) MR tablet and the 240 mg IR tablet (reference), respectively. Periods 3, 4, 5 and 6 will be flexible and the dosing regimen will be dependent on the outcome of Periods 1 and 2.


Eligibility criteria: Inclusion Criteria:

* Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
* Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
* Body weight greater than and equal to 50 kilogram (kg) and body mass index within the range 19.0 to 32.0 kilogram per meter square (kg/m\^2) (inclusive).
* A male subject must agree to use a highly effective contraception during the treatment period and for at least 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, not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive during the treatment period and for at least 30 days before and 30 days after the last dose of study treatment.
* Capable of giving signed informed consent.

Exclusion Criteria:

* History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), 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.
* Parts A and C only: Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a subject's lifetime.
* Part B only: Subjects with current history of suicidal ideation behavior as measured using the columbia-suicide severity rating scale (C-SSRS) or a history of attempted suicide.
* History of clinically significant psychiatric disorders as judged by the investigator. Depression requiring treatment in the last 2 years.
* History of herpes zoster (shingles) reactivation.
* History or diagnosis of obstructive sleep apnea.
* History of a significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
* History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
* A positive diagnostic tuberculosis (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.
* History of GI surgery (with exception of appendectomy).
* History of cholecystectomy or gall stones.
* Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
* ALT greater than 1.5 times upper limit of normal (ULN).
* Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35 percentage of total).
* Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
* Corrected QT interval (QTc) greater than 450 millisecond (msec).
* Past or intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing (paracetamol/acetaminophen \[up to 2 gram (g) per day\], hormone replacement therapy and hormonal contraception are permitted).
* Live or attenuated vaccine(s) within 30 days of enrolment, 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.
* Subject in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within a 56 day period; therefore donation or loss of greater than 400 mL of blood within the previous 3 months.
* Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
* Current enrolment or past participation within the last 3 months before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
* Subjects who have previously been enrolled in this study. Subjects in Part A of this study are not permitted to participate in Part B. Subjects in Parts A or B of this study are not permitted to participate in Part C.
* Current or history of renal disease or estimated glomerular filtration rate (GFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation calculation less than 60 mL/minutes(min)/1.73m\^2 at screening.
* Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening or within 3 months prior to first dose. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of hepatitis B core antibody (HBcAb) should be excluded. Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
* An elevated C-reactive protein (CRP) outside the normal reference range.
* Part B only: A positive anti-nuclear antibody (ANA) outside the normal reference range.
* Confirmed positive pre-study drug/alcohol screen.
* Positive human immunodeficiency virus (HIV) antibody test.
* Regular use of known drugs of abuse, or history of drug or alcohol abuse in the past 5 years.
* Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of greater than 21 units for males or greater than 14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
* Current use or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening. A carbon monoxide breath test reading of greater than 10 parts per million (ppm).
* Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
* Unwilling or unable to swallow multiple size 0-00 capsules as part of study participation.
* Subjects who do not have suitable veins for multiple venipunctures/cannulation as assessed by the investigator at screening.
* Total cholesterol greater than or equal to 300 milligram/deciliter (mg/dL) (greater than or equal to 7.77 millimoles per liter \[mmol\]/L\]) or triglycerides greater than or equal to 250 mg/dL (greater than or equal to 2.82 mmol/L).
* Subjects who are study site employees, or immediate family members of a study site or sponsor employee.

Primary outcomes:
measure: Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK2982772 in IR Formulation: Part A
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
measure: AUC(0-inf) of GSK2982772 in MT Formulation :Part A
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK2982772 in IR Formulation : Part A
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
measure: AUC(0-t) of GSK2982772 in MT Formulation: Part A
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: Area Under the Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK2982772 in IR Formulation: Part A
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
measure: AUC(0-24) of GSK2982772 in MT Formulation: Part A
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: Area Under the Curve From Time Zero to 12 Hours (AUC[0-12]) of GSK2982772 in IR Formulation: Part A
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours post-dose
measure: AUC(0-12) of GSK2982772 in MT Formulation: Part A
timeFrame: Pre-dose, 2, 4, 6, 8, 10, and 12 hours post-dose
measure: Maximum Observed Concentration (Cmax) of GSK2982772 in IR Formulation: Part A
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
measure: Cmax of GSK2982772 in MT Formulation: Part A
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: Concentration at 12 Hours Post-dose (C12hour) of GSK2982772 in Part A
timeFrame: 12 hours post-dose
measure: Concentration at 24 Hours Post-dose (C24hour) of GSK2982772 in Part A
timeFrame: 24 hours post-dose
measure: Relative Bioavailability (Frelformulation) Based on AUC (0-inf) of GSK2982772 in Part A
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose (reference); Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose (test)
measure: Frelformulation Based on AUC (0-24) of GSK2982772 in Part A
timeFrame: Pre-dose 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose (reference); Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, and 24 hours post-dose (test)
measure: Frelformulation Based on Cmax of GSK2982772 in Part A
timeFrame: Pre-dose,0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose(reference); Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose(test)
measure: Ratio of Cmax to C12hour of GSK2982772 in IR Formulation: Part A
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 26, 28, 30 and 32 hours post-dose
measure: Ratio of Cmax to C12hour of GSK2982772 in MT Formulation: Part A
timeFrame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: Ratio of Cmax to C24hour of GSK2982772 in IR Formulation: Part A
timeFrame: Pre-dose 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
measure: Ratio of Cmax to C24hour of GSK2982772 in MT Formulation: Part A
timeFrame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: Time to Cmax (Tmax) of GSK2982772 in IR Formulation: Part A
timeFrame: Pre-dose 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
measure: Tmax of GSK2982772 in MT Formulation: Part A
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: AUC(0-inf) of GSK2982772 for IR Formulation in Part C: Fasted State
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: AUC(0-inf) of GSK2982772 for MM Formulation in Part C: Fasted State
timeFrame: Pre-dose, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: AUC(0-t) of GSK2982772 for IR Formulation in Part C: Fasted State
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: AUC(0-t) of GSK2982772 for MM Formulation in Part C: Fasted State
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: AUC(0-24) of GSK2982772 for IR Formulation in Part C: Fasted State
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: AUC(0-24) of GSK2982772 for MM Formulation in Part C: Fasted State
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours post-dose
measure: AUC (0-12) of GSK2982772 for IR Formulation in Part C: Fasted State
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose
measure: AUC (0-12) of GSK2982772 for MM Formulation in Part C: Fasted State
timeFrame: Pre-dose, 2, 4, 6, 8, 10, and 12 hours post-dose
measure: Cmax of GSK2982772 for IR Formulation in Part C: Fasted State
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Cmax of GSK2982772 for MM Formulation in Part C: Fasted State
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: C12 of GSK2982772 in Part C: Fasted State
timeFrame: 12 hours post-dose
measure: C24 of GSK2982772 in Part C: Fasted State
timeFrame: 24 hours post-dose
measure: Ratio of Cmax to C12hour of GSK2982772 for IR Formulation in Part C: Fasted State
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Ratio of Cmax to C12hour of GSK2982772 for MM Formulation in Part C: Fasted State
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: Ratio of Cmax to C24hour of GSK2982772 for IR Formulation in Part C: Fasted State
timeFrame: Pre-dose,0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Ratio of Cmax to C24hour of GSK2982772 for MM Formulation in Part C: Fasted State
timeFrame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: Frelformulation Based on AUC (0-t) of GSK2982772 in Part C: Fasted State
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose(reference); Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose(test)
measure: Frelformulation Based on AUC (0-24) of GSK2982772 in Part C: Fasted State
timeFrame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose(reference); Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours post-dose(test)
Secondary outcomes:
measure: Frelformulation Based on AUC (0-inf) of GSK2982772 After a High Fat Meal in Part A
timeFrame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: Frelformulation Based on Cmax of GSK2982772 After a High Fat Meal in Part A
timeFrame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose
measure: AUC(0-24) of GSK2982772 in Part B
timeFrame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3
measure: Cmax of GSK2982772 in Part B
timeFrame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3
measure: Tmax of GSK2982772 in Part B
timeFrame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3
measure: AUC (0-24) of GSK2982772 After Meal in Part C
timeFrame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose
measure: Cmax of GSK2982772 After Meal in Part C
timeFrame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours
measure: C12 of GSK2982772 After Meal in Part C
timeFrame: 12 hours post-dose
measure: AUC(0-t) of GSK2982772 After Meal in Part C
timeFrame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: AUC(0-inf) of GSK2982772 After Meal in Part C
timeFrame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: AUC(0-12) of GSK2982772 After Meal in Part C
timeFrame: Pre-dose and at 2, 4, 6, 8, 10, and 12 hours post-dose
measure: Frelformulation Based on AUC (0-t) of GSK2982772 After Meal in Part C
timeFrame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: Frelformulation Based on Cmax of GSK2982772 After Meal in Part C
timeFrame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: Tmax of GSK2982772 After Meal in Part C
timeFrame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose
measure: Number of Participants With Adverse Events (AE) and Serious AEs (SAE) in Part A
timeFrame: Up to Day 43
measure: Number of Participants With AE and SAE in Part B
timeFrame: Up to Day 22
measure: Number of Participants With AE and SAE in Part C
timeFrame: Up to Day 43
measure: Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part A
timeFrame: Up to Day 43
measure: Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part A
timeFrame: Up to Day 43
measure: Number of Participants Abnormal Urinalysis Dipstick Results: Part A
timeFrame: Up to Day 43
measure: Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part B
timeFrame: Up to Day 22
measure: Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part B
timeFrame: Up to Day 22
measure: Number of Participants Abnormal Urinalysis Dipstick Results: Part B
timeFrame: Up to Day 22
measure: Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part C
timeFrame: Up to Day 43
measure: Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part C
timeFrame: Up to Day 43
measure: Number of Participants Abnormal Urinalysis Dipstick Results: Part C
timeFrame: Up to Day 43
measure: Number of Participants Abnormal Electrocardiogram (ECG) Findings: Part A
timeFrame: Up to Day 43
measure: Number of Participants Abnormal ECG Findings: Part B
timeFrame: Up to Day 22
measure: Number of Participants Abnormal ECG Findings: Part C
timeFrame: Up to Day 43
measure: Change From Baseline in Blood Pressure: Part A
timeFrame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
measure: Change From Baseline in Heart Rate: Part A
timeFrame: Baseline (Day 1 Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
measure: Change From Baseline in Respiration Rate: Part A
timeFrame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
measure: Change From Baseline in Body Temperature: Part A
timeFrame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
measure: Change From Baseline in Blood Pressure: Part B
timeFrame: Baseline (Day 1, Pre-dose), Day 1 and Day 3: 2 and 12 hours; Pre-dose on Days 2 and 3; Day 4: 24 hours
measure: Change From Baseline in Heart Rate: Part B
timeFrame: Baseline (Day 1, Pre-dose), Day 1 and Day 3: 2 and 12 hours; Pre-dose on Days 2 and 3; Day 4: 24 hours
measure: Change From Baseline in Respiration Rate: Part B
timeFrame: Baseline (Day 1, Pre-dose), Day 1 and Day 3: 2 and 12 hours; Pre-dose on Days 2 and 3; Day 4 24 hours
measure: Change From Baseline in Body Temperature: Part B
timeFrame: Baseline (Day 1, Pre-dose), Day 1 and Day 3: 2 and 12 hours; Pre-dose on Days 2 and 3; Day 4: 24 hours
measure: Change From Baseline in Blood Pressure: Part C
timeFrame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
measure: Change From Baseline in Heart Rate: Part C
timeFrame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
measure: Change From Baseline in Respiration Rate: Part C
timeFrame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
measure: Change From Baseline in Body Temperature: Part C
timeFrame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Tompson DJ, Whitaker M, Pan R, Johnson G, Fuller T, McKenzie L, Zann V, Powell M, Abbott-Banner K, Hawkins S. Development of a Prototype, Once-Daily, Modified-Release Formulation for the Short Half-Life RIPK1 Inhibitor GSK2982772. Pharm Res. 2021 Jul;38(7):1235-1245. doi: 10.1007/s11095-021-03059-z. Epub 2021 Jun 16.