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A Safety and Pharmacokinetic (PK) Study of GSK2982772 in Healthy Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03305419
Recruitment Status : Completed
First Posted : October 10, 2017
Results First Posted : November 1, 2019
Last Update Posted : November 1, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This study is designed to evaluate the safety, tolerability and PK of GSK2982772, in repeat oral doses in healthy subjects. This study is being conducted to support administration of higher dose levels of GSK2982772 than initially studied in the First Time in Human (FTiH) study. This study will also assess the impact of food during the repeat doses of GSK2982772. This will be a two part study; Part A and Part B. Part A (cohort 1) - single ascending dose, randomized, placebo-controlled, 3-way crossover. Part B (cohorts 2, 3, 4 and 5) - repeat dose, randomized, placebo-controlled, sequential-group. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in crossover manner on Day 1 of each of the three periods in Part A. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohort 2 of Part B and in 9:5 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohorts 3, 4 and 5 of Part B. Approximately 66 subjects will be included in this study. The study duration, including screening and follow-up, will not be expected to exceed 13 weeks for Part A and 8 weeks for Part B.

Condition or disease Intervention/treatment Phase
Autoimmune Diseases Drug: GSK2982772 capsule Drug: Placebo capsule Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 62 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: This study will consist of two parts; Part A and Part B. Part A will be a 3-way crossover design and Part B will be a sequential-group design.
Masking: Double (Participant, Investigator)
Masking Description: This will be a double-blind study. Subjects and investigator will be masked.
Primary Purpose: Treatment
Official Title: A Single-centre, Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK2982772 in Repeat Oral Doses in Healthy Subjects
Actual Study Start Date : October 11, 2017
Actual Primary Completion Date : October 15, 2018
Actual Study Completion Date : October 15, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Subjects receiving treatment sequence ABC in cohort 1: Part A
Eligible subjects will be randomized to receive treatment sequence ABC in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens.
Drug: GSK2982772 capsule
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.

Drug: Placebo capsule
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.

Experimental: Subjects receiving treatment sequence ABP in cohort 1: Part A
Eligible subjects will be randomized to receive treatment sequence ABP in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and P= Placebo. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens.
Drug: GSK2982772 capsule
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.

Drug: Placebo capsule
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.

Experimental: Subjects receiving treatment sequence APC in cohort 1: Part A
Eligible subjects will be randomized to receive treatment sequence APC in Part A; A= GSK2982772 120 mg TID, P= Placebo and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens.
Drug: GSK2982772 capsule
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.

Drug: Placebo capsule
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.

Experimental: Subjects receiving treatment sequence PBC in cohort 1: Part A
Eligible subjects will be randomized to receive treatment sequence PBC in Part A; P= Placebo, B= GSK2982772 240 mg TID and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens.
Drug: GSK2982772 capsule
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.

Drug: Placebo capsule
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.

Experimental: Subjects receiving GSK2982772 120 mg TID in cohort 2 : Part B
Eligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B.
Drug: GSK2982772 capsule
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.

Experimental: Subjects receiving GSK2982772 120 mg TID in cohort 3 : Part B
Eligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B.
Drug: GSK2982772 capsule
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.

Experimental: Subjects receiving GSK2982772 240 mg TID in cohort 4: Part B
Eligible subjects will receive GSK2982772 oral capsule with a dose of 240 mg TID for 14 days in Part B.
Drug: GSK2982772 capsule
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.

Experimental: Subjects receiving GSK2982772 360 mg BID in cohort 5: Part B
Eligible subjects will receive GSK2982772 oral capsule with a dose of 360 mg BID for 14 days in Part B.
Drug: GSK2982772 capsule
GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.

Placebo Comparator: Subjects receiving placebo in cohort 2 : Part B
Subjects will receive placebo oral capsule for 14 days in Part B.
Drug: Placebo capsule
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.

Placebo Comparator: Subjects receiving placebo in cohort 3 : Part B
Subjects will receive placebo oral capsule for 14 days in Part B.
Drug: Placebo capsule
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.

Placebo Comparator: Subjects receiving placebo in cohort 4 : Part B
Subjects will receive placebo oral capsule for 14 days in Part B.
Drug: Placebo capsule
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.

Placebo Comparator: Subjects receiving placebo in cohort 5: Part B
Subjects will receive placebo oral capsule for 14 days in Part B.
Drug: Placebo capsule
Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.




Primary Outcome Measures :
  1. Number of Subjects With Adverse Events (AEs) and Serious AEs (SAEs): Part A [ Time Frame: Up to Day 14 ]
    An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.

  2. Number of Participants With AEs and SAEs: Part B [ Time Frame: Up to Day 28 ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.

  3. Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part A [ Time Frame: Up to Week 9 ]
    Blood samples were collected from participants for the analysis of following clinical chemistry parameters: alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times Upper Limit of Normal (ULN) units per liter (U/L) for ALT, <30 grams per liter (g/L) for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 millimoles per liter (mmol/L) for calcium, >44.2 micromoles per liter (µmol/L) for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.

  4. Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part B [ Time Frame: Up to Week 4 ]
    Blood samples were collected from participants for the analysis of following clinical chemistry parameters: ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times ULN U/L for ALT, <30 g/L for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 mmol/L for calcium, >44.2 µmol/L for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.

  5. Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part A [ Time Frame: Up to Week 9 ]
    Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and white blood cell (WBC) counts. PCI ranges were >0.54 or < 0.075 proportion of red blood cells (RBC) in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.

  6. Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part B [ Time Frame: Up to Week 4 ]
    Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and WBC counts. PCI ranges were >0.54 or < 0.075 proportion of RBC in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.

  7. Number of Participants With Worst Case Urinalysis Results: Part A [ Time Frame: Up to Week 9 ]
    Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.

  8. Number of Participants With Worst Case Urinalysis Results: Part B [ Time Frame: Up to Week 4 ]
    Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.

  9. Number of Participants With Abnormal Vital Signs: Part A [ Time Frame: Up to Week 9 ]
    Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 millimeters of mercury [mmHg]), diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.

  10. Number of Participants With Abnormal Vital Signs: Part B [ Time Frame: Up to Week 4 ]
    Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 mmHg, diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.

  11. Number of Participants With Abnormal Electrocardiogram (ECG) Findings: Part A [ Time Frame: Up to Day 4 ]
    12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. 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.

  12. Number of Participants With Abnormal ECG Findings: Part B [ Time Frame: Up to Week 4 ]
    12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. 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.


Secondary Outcome Measures :
  1. Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC[0-24]) Following TID Dosing of GSK2982772: Part A [ Time Frame: Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day1 ]
    Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  2. AUC(0-24) Following BID Dosing of GSK2982772: Part A [ Time Frame: Pre-dose, 20min, 40min, 1hr, 1hr 30min, 2hr, 3hr, 4hr, 6hr, 8hr, 10hr, 12hr, 12hr 20min, 12hr 40min, 13hr, 13hr 30min, 14hr, 15hr, 16hr, 19hr, 22hr, 24hr post dose on Day 1. ]
    Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  3. AUC[0-24] Following TID Dosing of GSK2982772: Part B [ Time Frame: Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day14 ]
    Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  4. AUC (0-7) Following TID Dosing of GSK2982772 : Part A [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Day 1 ]
    Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  5. AUC (7-14) Following TID Dosing of GSK2982772 : Part A [ Time Frame: 7 hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 1 ]
    Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  6. AUC (14-24) Following TID Dosing of GSK2982772 : Part A [ Time Frame: 14 hours, 14 hours 20 and 40 minutes, 15 hours ,15 hours 30 minutes, 16, 19, 22 and 24 hours on Day 1 ]
    Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  7. AUC (0-12) Following BID Dosing of GSK2982772 in Part A [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours,12 hours on Day 1 ]
    Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  8. AUC (12-24) Following BID Dosing of GSK2982772 in Part A [ Time Frame: 12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours on Day 1 ]
    Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  9. AUC(0-7) Following TID Dosing of GSK2982772 in Part B [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 1 and 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  10. AUC (7-14) Following TID Dosing of GSK2982772 in Part B [ Time Frame: 7 and 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  11. AUC (14-24) Following TID Dosing of GSK2982772 in Part B [ Time Frame: 14 hours, 14 hours 20 minutes, 14 hours 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  12. Maximum Observed Plasma Drug Concentration Cmax (0-7) Following TID Dosing of GSK2982772 in Part A [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  13. Cmax (7-14) Following TID Dosing of GSK2982772 in Part A [ Time Frame: 7 hours, 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  14. Cmax (14-24) Following TID Dosing of GSK2982772 in Part A [ Time Frame: 14 hours, 14 hours 20 and 40 minutes, 15 and 15 hours 30 minutes, 16, 19, 22 and 24 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  15. Cmax (0-12) Following BID Dosing of GSK2982772 in Part A [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  16. Cmax (12-24) Following BID Dosing of GSK2982772 in Part A [ Time Frame: 12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  17. Cmax (0-7) Following TID Dosing of GSK2982772 in Part B [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  18. Cmax (7-14) Following TID Dosing of GSK2982772 in Part B [ Time Frame: 7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  19. Cmax (14-24) Following TID Dosing of GSK2982772 in Part B [ Time Frame: 14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  20. Time to Cmax (Tmax) (0-7) Following TID Dosing of GSK2982772 in Part A [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  21. Tmax (7-14) Following TID Dosing of GSK2982772 in Part A [ Time Frame: 7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  22. Tmax (14-24) Following TID Dosing of GSK2982772 in Part A [ Time Frame: 14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  23. Tmax (0-12) Following BID Dosing of GSK2982772 in Part A [ Time Frame: Pre-dose, 20 and 40 minutes, 1hour, 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  24. Tmax (12-24) Following BID Dosing of GSK2982772 in Part A [ Time Frame: 12 hours, 12 hours 20 and 40 minutes, 13 hours, 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  25. Tmax (0-7) Following TID Dosing of GSK2982772 Part B [ Time Frame: Pre-dose, 20 and 40 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  26. Tmax (7-14) Following TID Dosing of GSK2982772 in Part B [ Time Frame: 7hours and 7 hours 20 and 40 minutes, 8hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  27. Tmax (14-24) Following TID Dosing of GSK2982772 in Part B [ Time Frame: 14hours, 14 hours 20 and 40 minutes, 15 hours and 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  28. Observed Trough Plasma Drug Concentration at 7 Hour (C7),Following TID Dosing of GSK2982772 in Part A [ Time Frame: 7 hours post-dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  29. Observed Trough Plasma Drug Concentration at 14 Hours (C14) Following TID Dosing of GSK2982772 in Part A [ Time Frame: 14 hours post-dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  30. C24 Following TID Dosing of GSK2982772 in Part A [ Time Frame: 24 hours post-dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  31. C12 Following BID Dosing of GSK2982772 in Part A [ Time Frame: 12 hours post-dose on Day 1 ]

    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

    Pharmacokinetic parameters were calculated by standard non-compartmental analysis.


  32. C24 Following BID Dosing of GSK2982772 in Part A [ Time Frame: 24 hours post-dose on Day 1 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  33. C0 Following TID Dosing of GSK2982772 in Part B [ Time Frame: Pre-dose on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  34. C7 Following TID Dosing of GSK2982772 in Part B [ Time Frame: 7 hours post-dose on Days 1 and 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  35. C14 Following TID Dosing of GSK2982772 in Part B [ Time Frame: 14 hours post-dose on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  36. C24 Following TID Dosing of GSK2982772 in Part B [ Time Frame: 24 hours post-dose on Day 14 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  37. AUC([0-7] Following TID Dosing of GSK2982772 in Fed State of Part B [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  38. Cmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  39. Tmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B [ Time Frame: Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11 ]
    Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.

  40. Ratio of Plasma 4 Beta-hydroxycholesterol to Cholesterol: Part B [ Time Frame: Pre-dose on Day 1 and 24 hours post first dose on Day 14 ]
    Blood samples were collected into EDTA tubes and processed to plasma for 4 beta-hydroxycholesterol and cholesterol. Ratio of 4 beta-hydroxycholesterol to cholesterol is presented



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
  • Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor (if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 30 kg per square meter (kg/m^2) (inclusive).
  • A male subject with a female partner of reproductive potential must agree to use 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, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance for a minimum of 28 days prior to the treatment period and for at least 30 days after the last administration of study drug. A WOCBP using a hormonal method of highly effective contraception must also agree to partner use of a male condom during the treatment period and for at least 30 days after the last administration of study drug.
  • Capable of giving signed informed consent.

Exclusion Criteria:

  • History or presence 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 of herpes zoster (shingles) reactivation.
  • Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration >5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
  • ALT >1.5 times upper limit of normal (ULN).
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • ECG QT interval corrected for heart rate (QTc) >450 millisecond (msec).
  • History of serious or recurrent infections or has had an active infection within 14 days of receiving study medication.
  • History of diagnosis of obstructive sleep apnoea or significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
  • Part A: History of active suicidal ideation behavior (SIB) within the past 6 months or any history of attempted suicide in a subject's lifetime.
  • History of current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
  • Past or intended use of over-the-counter or prescription medication, including herbal medications, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing.
  • Subject received a vaccine (either live attenuated or now-live) within 30 days prior to randomization, or plans to receive a live attenuated vaccine within 30 days + 5 half-lives (32 days) of the last dose of study medication.
  • Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within a 56-day period.
  • Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
  • Positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV1 and 2) antibody test.
  • Regular use of known drugs of abuse.
  • Subjects with impaired renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKS-EPI) Creatinine > 1.6 mg/deciliter (mg/dL) with an age appropriate glomerular filtration rate (GFR) <= 60 (mL/minute/1.73 m^2) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
  • An elevated C-reactive protein (CRP) outside of the normal reference range.
  • Regular alcohol consumption within 6 months prior to the study defined as: For United Kingdom (UK) - an average weekly intake of >14 units for males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
  • Cotinine or carbon monoxide levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • 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 00 capsules as part of study participation.

PART B Specific exclusion criteria:

  • History of SIB as measured using the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted suicide.
  • A positive anti-nuclear antibody (ANA) outside of the normal reference range.
  • Fasting total cholesterol >=300 mg/dL or triglycerides >=250 mg/dL.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03305419


Locations
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United Kingdom
GSK Investigational Site
Cambridge, United Kingdom, CB2 2GG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] February 26, 2018
Statistical Analysis Plan  [PDF] November 30, 2018

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03305419    
Other Study ID Numbers: 205184
2017-002662-45 ( EudraCT Number )
First Posted: October 10, 2017    Key Record Dates
Results First Posted: November 1, 2019
Last Update Posted: November 1, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Crossover
Sequential
GSK2982772
Safety
Pharmacokinetics
Healthy subjects
Additional relevant MeSH terms:
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Autoimmune Diseases
Immune System Diseases