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Completed

NCT Number: 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

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.

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Key information

Conditions

Autoimmune Diseases Immune System Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site

Nottingham, NG11 6JS, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

GSK2982772 Modified Release

Drug

GSK2982772 MR will be available as prototype MR minitablet in capsules with unit dose strength of 60 mg in Part A. In Part B, GSK2982772 MR minitablet in capsules with unit dose strength of 15, 30 or 60 mg will be administered by subjects for Days 1 to 3. In Part C, GSK2982772 MR tablet with unit dose strength of 240, 360 or 480 mg will be administered by subjects. GSK2982772 MR will be administered orally with 240 mL of water.

GSK2982772 Immediate Release

Drug

In part A, GSK2982772 IR tablet will be available with unit dose strength of 30 mg and the total dose administered by subjects will be 120 mg (4 tablets of dose strength 30 mg) orally with 240 mL of water. In part C, GSK2982772 IR tablet will be available with unit dose strength of 30 mg and the total dose administered by subjects will be 240 mg (8 tablets of dose strength 30 mg) orally with 240 mL of water.

Primary outcomes

  1. Area Under the Curve From Time Zero to Infinity (AUC[0-inf]) of GSK2982772 in IR Formulation: Part A

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf). Participants in the 'Safety Population' for whom a Pharmacokinetic (PK) sample was obtained and analyzed were part of PK Population.

  2. AUC(0-inf) of GSK2982772 in MT Formulation :Part A

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-inf).

  3. Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC[0-t]) of GSK2982772 in IR Formulation : Part A

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t)

  4. AUC(0-t) of GSK2982772 in MT Formulation: Part A

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-t)

  5. Area Under the Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK2982772 in IR Formulation: Part A

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24)

  6. AUC(0-24) of GSK2982772 in MT Formulation: Part A

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24)

  7. Area Under the Curve From Time Zero to 12 Hours (AUC[0-12]) of GSK2982772 in IR Formulation: Part A

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-12)

  8. AUC(0-12) of GSK2982772 in MT Formulation: Part A

    Time frame: Pre-dose, 2, 4, 6, 8, 10, and 12 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for AUC (0-12)

  9. Maximum Observed Concentration (Cmax) of GSK2982772 in IR Formulation: Part A

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for Cmax

  10. Cmax of GSK2982772 in MT Formulation: Part A

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for Cmax

  11. Concentration at 12 Hours Post-dose (C12hour) of GSK2982772 in Part A

    Time frame: 12 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for C12hour.

  12. Concentration at 24 Hours Post-dose (C24hour) of GSK2982772 in Part A

    Time frame: 24 hours post-dose

    Blood samples were collected from participants at indicated time points and analyzed for C24hour.

  13. Relative Bioavailability (Frelformulation) Based on AUC (0-inf) of GSK2982772 in Part A

    Time frame: 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)

    Blood samples were collected at indicated time points for analysis of Frelformulation. Frelformulation for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MT (test) / Geometric mean of AUC (0-inf) of IR Formulation (reference) multiplied by 100.

  14. Frelformulation Based on AUC (0-24) of GSK2982772 in Part A

    Time frame: 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)

    Blood samples were collected at indicated time points for analysis of Frelformulation. Frelformulation for AUC (0-24) was calculated as Geometric mean of AUC (0-24) of MT (test) / Geometric mean of AUC (0-24) of IR Formulation (reference) multiplied by 100.

  15. Frelformulation Based on Cmax of GSK2982772 in Part A

    Time frame: 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)

    Blood samples were collected at indicated time points for analysis of Frelformulation. Frel was calculated as Geometric mean of Cmax of MT Formulation (test)/ Geometric mean of Cmax of IR Formulation (reference) multiplied by 100.

  16. Ratio of Cmax to C12hour of GSK2982772 in IR Formulation: Part A

    Time frame: 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

    Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hour has been presented.

  17. Ratio of Cmax to C12hour of GSK2982772 in MT Formulation: Part A

    Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hour has been presented.

  18. Ratio of Cmax to C24hour of GSK2982772 in IR Formulation: Part A

    Time frame: Pre-dose 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hour has been presented.

  19. Ratio of Cmax to C24hour of GSK2982772 in MT Formulation: Part A

    Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hour has been presented.

  20. Time to Cmax (Tmax) of GSK2982772 in IR Formulation: Part A

    Time frame: Pre-dose 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of Tmax.

  21. Tmax of GSK2982772 in MT Formulation: Part A

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of Tmax.

  22. AUC(0-inf) of GSK2982772 for IR Formulation in Part C: Fasted State

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-inf)

  23. AUC(0-inf) of GSK2982772 for MM Formulation in Part C: Fasted State

    Time frame: Pre-dose, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-inf).

  24. AUC(0-t) of GSK2982772 for IR Formulation in Part C: Fasted State

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-t).

  25. AUC(0-t) of GSK2982772 for MM Formulation in Part C: Fasted State

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-t).

  26. AUC(0-24) of GSK2982772 for IR Formulation in Part C: Fasted State

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-24)

  27. AUC(0-24) of GSK2982772 for MM Formulation in Part C: Fasted State

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-24)

  28. AUC (0-12) of GSK2982772 for IR Formulation in Part C: Fasted State

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-12)

  29. AUC (0-12) of GSK2982772 for MM Formulation in Part C: Fasted State

    Time frame: Pre-dose, 2, 4, 6, 8, 10, and 12 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-12)

  30. Cmax of GSK2982772 for IR Formulation in Part C: Fasted State

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of Cmax

  31. Cmax of GSK2982772 for MM Formulation in Part C: Fasted State

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of Cmax

  32. C12 of GSK2982772 in Part C: Fasted State

    Time frame: 12 hours post-dose

    Blood samples was collected at indicated time point for analysis of C12

  33. C24 of GSK2982772 in Part C: Fasted State

    Time frame: 24 hours post-dose

    Blood samples was collected at indicated time point for analysis of C24

  34. Ratio of Cmax to C12hour of GSK2982772 for IR Formulation in Part C: Fasted State

    Time frame: Pre-dose, 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hours has been presented.

  35. Ratio of Cmax to C12hour of GSK2982772 for MM Formulation in Part C: Fasted State

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of ratio of Cmax to C12hour. Mean and standard deviation of ratio of Cmax to C12 hours has been presented.

  36. Ratio of Cmax to C24hour of GSK2982772 for IR Formulation in Part C: Fasted State

    Time frame: Pre-dose,0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hours has been presented.

  37. Ratio of Cmax to C24hour of GSK2982772 for MM Formulation in Part C: Fasted State

    Time frame: Pre-dose, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of ratio of Cmax to C24hour. Mean and standard deviation of ratio of Cmax to C24 hours has been presented.

  38. Frelformulation Based on AUC (0-t) of GSK2982772 in Part C: Fasted State

    Time frame: 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)

    Blood samples were collected at indicated time points for analysis of Frelformulation. Frel for AUC (0-t) was calculated as Geometric mean of AUC (0-t) of MM formulation (test) / Geometric mean of AUC (0-t) of IR Formulation (reference) multiplied by 100.

  39. Frelformulation Based on AUC (0-24) of GSK2982772 in Part C: Fasted State

    Time frame: 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)

    Blood samples were collected at indicated time points for analysis of Frelformulation. Frel for AUC (0-24) was calculated as Geometric mean of AUC (0-24) of MM Fasted formulation (test) / Geometric mean of AUC (0-24) of IR Formulation (reference) multiplied by 100.

Secondary outcomes

  1. Frelformulation Based on AUC (0-inf) of GSK2982772 After a High Fat Meal in Part A

    Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 after a high fat meal. Frel for AUC (0-inf) was calculated as Geometric mean of AUC (0-inf) of MT Fed formulation (test) / Geometric mean of AUC (0-inf) of MT Fasted Formulation (reference) multiplied by 100.

  2. Frelformulation Based on Cmax of GSK2982772 After a High Fat Meal in Part A

    Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of FrelFE based on AUC of GSK2982772 after a high fat meal. Frel for Cmax was calculated as Geometric mean of Cmax of MT Fed formulation (test) / Geometric mean of Cmax of MT Fasted Formulation (reference) multiplied by 100.

  3. AUC(0-24) of GSK2982772 in Part B

    Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3

    Blood samples were collected at indicated time points for analysis of AUC (0-24)

  4. Cmax of GSK2982772 in Part B

    Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3

    Blood samples were collected at indicated time points for analysis of Cmax

  5. Tmax of GSK2982772 in Part B

    Time frame: Pre-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 hours on Day 1 and Day 3

    Blood samples were collected at indicated time points for analysis of Tmax

  6. AUC (0-24) of GSK2982772 After Meal in Part C

    Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, and 24 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-24)

  7. Cmax of GSK2982772 After Meal in Part C

    Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours

    Blood samples were collected at indicated time points for analysis of Cmax

  8. C12 of GSK2982772 After Meal in Part C

    Time frame: 12 hours post-dose

    Blood samples were collected at indicated time points for analysis of C12

  9. AUC(0-t) of GSK2982772 After Meal in Part C

    Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-t)

  10. AUC(0-inf) of GSK2982772 After Meal in Part C

    Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-inf) after meal.

  11. AUC(0-12) of GSK2982772 After Meal in Part C

    Time frame: Pre-dose and at 2, 4, 6, 8, 10, and 12 hours post-dose

    Blood samples were collected at indicated time points for analysis of AUC (0-12) after meal.

  12. Frelformulation Based on AUC (0-t) of GSK2982772 After Meal in Part C

    Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of Frelformulation based on AUC of GSK2982772 after meal. Frel for Auc (0-t) was calculated as Geometric mean of AUC (0-t) of MM Fed formulation (fed) / Geometric mean of AUC (0-t) of MM Fasted Formulation (fasted) multiplied by 100.

  13. Frelformulation Based on Cmax of GSK2982772 After Meal in Part C

    Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of Frelformulation based on Cmax of GSK2982772 after meal. Frel for Cmax was calculated as Geometric mean of Cmax of MM Fed formulation (test) / Geometric mean of Cmax of MM Fasted Formulation (reference) multiplied by 100.

  14. Tmax of GSK2982772 After Meal in Part C

    Time frame: Pre-dose and at 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30 and 32 hours post-dose

    Blood samples were collected at indicated time points for analysis of Tmax of GSK2982772 after meal.

  15. Number of Participants With Adverse Events (AE) and Serious AEs (SAE) in Part A

    Time frame: Up to Day 43

    An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before. All participants who receive at least 1 dose of study treatment and were included in Safety Population. Participants will be analyzed according to the treatment they actually received.

  16. Number of Participants With AE and SAE in Part B

    Time frame: Up to Day 22

    An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before.

  17. Number of Participants With AE and SAE in Part C

    Time frame: Up to Day 43

    An AE is any untoward medical occurrence in a clinical study participants, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly or birth defect and important medical events may jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed before.

  18. Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part A

    Time frame: Up to Day 43

    Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin and calcium. Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal baseline value. Clinical chemistry parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.

  19. Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part A

    Time frame: Up to Day 43

    Blood samples were collected to analyze hematology parameters like platelet count, white blood cell (WBC) count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.

  20. Number of Participants Abnormal Urinalysis Dipstick Results: Part A

    Time frame: Up to Day 43

    Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.

  21. Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part B

    Time frame: Up to Day 22

    Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, AST, ALT, ALP, total bilirubin and calcium. Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.

  22. Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part B

    Time frame: Up to Day 22

    Blood samples were collected to analyze hematology parameters like platelet count, WBC count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the subject has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing baseline value are assumed to have normal baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.

  23. Number of Participants Abnormal Urinalysis Dipstick Results: Part B

    Time frame: Up to Day 22

    Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.

  24. Number of Participants With Emergent Clinical Chemistry Results by Potential Clinical Importance Criteria: Part C

    Time frame: Up to Day 43

    Blood samples were collected for analysis of clinical chemistry parameters like albumin, creatinine, glucose, potassium, sodium, AST, ALT, ALP, total bilirubin and calcium. Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal Baseline value. Clinical chemistry parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.

  25. Number of Participants With Emergent Hematology Results by Potential Clinical Importance Criteria: Part C

    Time frame: Up to Day 43

    Blood samples were collected to analyze hematology parameters like platelet count, WBC count, hemoglobin, hematocrit, total neutrophils, and lymphocytes. Participants are counted in the worst case category that their value changes to (Low, Normal or High), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants are counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. Participants with missing Baseline value are assumed to have normal Baseline value. Hematology parameters with potential clinical importance data has been reported. Data for worst-case post-Baseline has been reported.

  26. Number of Participants Abnormal Urinalysis Dipstick Results: Part C

    Time frame: Up to Day 43

    Urine samples were collected for analysis of specific gravity, potential of hydrogen ions, glucose, protein, blood and ketones by dipstick method. Microscopic examination were performed if blood or protein values were abnormal.

  27. Number of Participants Abnormal Electrocardiogram (ECG) Findings: Part A

    Time frame: Up to Day 43

    Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and Corrected QT (QTc) intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.

  28. Number of Participants Abnormal ECG Findings: Part B

    Time frame: Up to Day 22

    Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and QTc intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.

  29. Number of Participants Abnormal ECG Findings: Part C

    Time frame: Up to Day 43

    Single 12-lead ECGs was obtained using an ECG machine. PR, QRS, QT and QTc intervals were measured in semi-supine or supine position. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. Data for worst-case post-Baseline has been reported.

  30. Change From Baseline in Blood Pressure: Part A

    Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours

    Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  31. Change From Baseline in Heart Rate: Part A

    Time frame: Baseline (Day 1 Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours

    Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  32. Change From Baseline in Respiration Rate: Part A

    Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours

    Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value

  33. Change From Baseline in Body Temperature: Part A

    Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours

    Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  34. Change From Baseline in Blood Pressure: Part B

    Time frame: 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

    SBP and DBP was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  35. Change From Baseline in Heart Rate: Part B

    Time frame: 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

    Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  36. Change From Baseline in Respiration Rate: Part B

    Time frame: 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

    Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value

  37. Change From Baseline in Body Temperature: Part B

    Time frame: 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

    Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  38. Change From Baseline in Blood Pressure: Part C

    Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours

    SBP and DBP was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  39. Change From Baseline in Heart Rate: Part C

    Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours

    Heart rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  40. Change From Baseline in Respiration Rate: Part C

    Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours

    Respiration rate was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

  41. Change From Baseline in Body Temperature: Part C

    Time frame: Baseline (Day 1, Pre-dose), Day 1: 2 and 12 hours; Day 2: 24hours

    Body temperature was measured in semi-supine position. Baseline is defined as the latest pre-dose assessment before entering study. Change from Baseline was defined as post-dose visit value minus Baseline value.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Collaborators

  • Quotient Clinical

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Aug 30, 2017
Registry last updated
Aug 13, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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