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Trial record 20 of 181 for:    RET

A Phase 1, First Time in Human (FTIH) Study to Evaluate GSK3352589, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Volunteers

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: NCT03154086
Recruitment Status : Completed
First Posted : May 15, 2017
Results First Posted : August 9, 2019
Last Update Posted : August 9, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Irritable Bowel Syndrome
Interventions Drug: GSK3352589
Drug: Matching Placebo
Enrollment 68
Recruitment Details This was a two-part study. Part A was a single dose escalating and Part B was a repeat dose escalating. Participants participated in either Part A or Part B of the study. This was a single center study, conducted at one site in Australia.
Pre-assignment Details A total number of 28 participants were enrolled in Part A and 40 participants were enrolled in Part B of the study. Participants in Part A, participated in one of the 3 Cohorts in Part A and Part B participants participated in one of the 5 Cohorts in Part B.
Arm/Group Title Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg Part A:Cohort 1:GSK3352589 2mg/Placebo/GSK3352589 15mg/50mg Part A:Cohort 1: GSK3352589 2mg/ 5mg/Placebo/ GSK3352589 50mg Part A:Cohort 1:GSK3352589 2mg/5mg/15mg/Placebo Part A:Cohort 2:GSK3352589 25 mg Fasted/GSK3352589 25 mg Fed Part A: Cohort 2: Placebo Fasted/Placebo Fed Part A:Cohort 3: GSK3352589 150 mg/Placebo Part A:Cohort 3: Placebo /GSK3352589 400 mg Part A:Cohort 3: GSK3352589 150 mg/GSK3352589 400 mg Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description Participants received single oral dose of placebo tablet in Period 1 followed by GSK3352589 5 milligrams (mg) tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by Placebo tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by Placebo tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by Placebo tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 25 mg tablet in Period 1 (fasted state) and in Period 2 (fed state). Participants returned for their next scheduled dosing Period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of placebo tablet matching GSK3352589 25 mg in Period 1 (fasted state) and in Period 2 (fed state). Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 150 mg tablet in Period 1 followed by placebo tablet matching GSK3352589 150 mg in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of placebo tablet matching GSK3352589 400 mg in Period 1 followed by single oral dose of GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 150 mg tablet in Period 1 followed by GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received repeat oral doses of placebo BID (twice a day) tablet administered for 14 days in Part B of the study. Participants received repeat oral doses of GSK3352589 5 mg BID tablet administered for 14 days in Part B of the study. Participants received repeat oral doses of GSK3352589 15 mg BID tablet administered for 14 days in Part B of the study. Participants received repeat oral doses of GSK3352589 50 mg BID tablet administered for 14 days in Part B of the study. Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study. Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Period Title: Part A: Cohort1 Period1 (Up to 3 Days)
Started 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0
Completed 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Part A: Cohort1 Washout1 (Up to 14 Days)
Started 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0
Completed 2 2 2 1 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 1 0 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Protocol Violation             0             0             0             1             0             0             0             0             0             0             0             0             0             0             0
Period Title: Part A: Cohort1 Period2 (Up to 3 Days)
Started 2 2 2 2 [1] 0 0 0 0 0 0 0 0 0 0 0
Completed 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
[1]
One replacement participant (par) was enrolled and dosed
Period Title: PartA: Cohort1 Washout2 (Up to 14 Days)
Started 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0
Completed 2 1 2 2 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 1 0 0 0 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             1             0             0             0             0             0             0             0             0             0             0             0             0             0
Period Title: Part A: Cohort1 Period3 (Up to 3 Days)
Started 2 2 [1] 2 2 0 0 0 0 0 0 0 0 0 0 0
Completed 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
[1]
One replacement par was enrolled and dosed
Period Title: Part A: Cohort1 Washout3 (Up to 14 Days)
Started 2 2 2 2 0 0 0 0 0 0 0 0 0 0 0
Completed 2 2 1 2 0 0 0 0 0 0 0 0 0 0 0
Not Completed 0 0 1 0 0 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             0             0             1             0             0             0             0             0             0             0             0             0             0             0             0
Period Title: Part A: Cohort1 Period4 (Up to 3 Days)
Started 3 [1] 2 1 2 0 0 0 0 0 0 0 0 0 0 0
Completed 2 2 1 2 0 0 0 0 0 0 0 0 0 0 0
Not Completed 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Reason Not Completed
Protocol Violation             1             0             0             0             0             0             0             0             0             0             0             0             0             0             0
[1]
1 par was not dosed on day of dosing due to elevated lab; hence 1 replacement was enrolled and dosed
Period Title: Part A: Cohort2 Period1 (Up to 3 Days)
Started 0 0 0 0 6 2 0 0 0 0 0 0 0 0 0
Completed 0 0 0 0 6 2 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Part A: Cohort2 Washout1 (Up to 14 Days)
Started 0 0 0 0 6 2 0 0 0 0 0 0 0 0 0
Completed 0 0 0 0 6 2 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Part A: Cohort2 Period2 (Up to 3 Days)
Started 0 0 0 0 6 2 0 0 0 0 0 0 0 0 0
Completed 0 0 0 0 6 2 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Part A: Cohort3 Period1 (Up to 3 Days)
Started 0 0 0 0 0 0 2 2 4 0 0 0 0 0 0
Completed 0 0 0 0 0 0 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Part A: Cohort3 Washout1 (Up to 14 Days)
Started 0 0 0 0 0 0 2 2 4 0 0 0 0 0 0
Completed 0 0 0 0 0 0 2 2 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Period Title: Part A: Cohort3 Period2 (Up to 3 Days)
Started 0 0 0 0 0 0 2 2 5 [1] 0 0 0 0 0 0
Completed 0 0 0 0 0 0 2 1 4 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0
Reason Not Completed
Withdrawal by Subject             0             0             0             0             0             0             0             0             1             0             0             0             0             0             0
Protocol Violation             0             0             0             0             0             0             0             1             0             0             0             0             0             0             0
[1]
1 par was unwell on Day-1 of Period 2 and discontinued; hence,1 replacement was enrolled and dosed
Period Title: Part B (Up to 25 Days)
Started 0 0 0 0 0 0 0 0 0 10 6 6 6 6 6
Completed 0 0 0 0 0 0 0 0 0 10 5 6 6 6 6
Not Completed 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             0             0             0             0             0             1             0             0             0             0
Arm/Group Title Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg Part A:Cohort 1:GSK3352589 2mg/Placebo/GSK3352589 15mg/50mg Part A:Cohort 1: GSK3352589 2mg/ 5mg/Placebo/ GSK3352589 50mg Part A:Cohort 1:GSK3352589 2mg/5mg/15mg/Placebo Part A:Cohort 2:GSK3352589 25 mg Fasted/GSK3352589 25 mg Fed Part A: Cohort 2: Placebo Fasted/Placebo Fed Part A:Cohort 3: GSK3352589 150 mg/Placebo Part A:Cohort 3: Placebo /GSK3352589 400 mg Part A:Cohort 3: GSK3352589 150 mg/GSK3352589 400 mg Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID Total
Hide Arm/Group Description Participants received single oral dose of placebo tablet in Period 1 followed by GSK3352589 5 milligrams (mg) tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by Placebo tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by Placebo tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by Placebo tablet in Period 4 of Cohort 1 in Part A of the study. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 25 mg tablet in Period 1 (fasted state) and in Period 2 (fed state). Participants returned for their next scheduled dosing Period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of placebo tablet matching GSK3352589 25 mg in Period 1 (fasted state) and in Period 2 (fed state). Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 150 mg tablet in Period 1 followed by placebo tablet matching GSK3352589 150 mg in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of placebo tablet matching GSK3352589 400 mg in Period 1 followed by single oral dose of GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received single oral dose of GSK3352589 150 mg tablet in Period 1 followed by GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Participants returned for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Participants received repeat oral doses of placebo BID (twice a day) tablet administered for 14 days in Part B of the study. Participants received repeat oral doses of GSK3352589 5 mg BID tablet administered for 14 days in Part B of the study. Participants received repeat oral doses of GSK3352589 15 mg BID tablet administered for 14 days in Part B of the study. Participants received repeat oral doses of GSK3352589 50 mg BID tablet administered for 14 days in Part B of the study. Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study. Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study. Total of all reporting groups
Overall Number of Baseline Participants 3 3 2 3 6 2 2 2 5 10 6 6 6 6 6 68
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 3 participants 3 participants 2 participants 3 participants 6 participants 2 participants 2 participants 2 participants 5 participants 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants 68 participants
43.0  (14.00) 26.7  (4.73) 33.5  (9.19) 41.0  (5.20) 29.7  (8.57) 34.5  (3.54) 40.5  (7.78) 44.5  (0.71) 28.8  (7.43) 25.5  (5.40) 30.8  (8.11) 33.3  (8.45) 23.3  (2.88) 23.7  (4.59) 32.2  (11.20) 30.5  (8.95)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 2 participants 3 participants 6 participants 2 participants 2 participants 2 participants 5 participants 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants 68 participants
Female
0
   0.0%
0
   0.0%
1
  50.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
2
   2.9%
Male
3
 100.0%
3
 100.0%
1
  50.0%
3
 100.0%
6
 100.0%
2
 100.0%
2
 100.0%
2
 100.0%
5
 100.0%
10
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
6
 100.0%
5
  83.3%
66
  97.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 2 participants 3 participants 6 participants 2 participants 2 participants 2 participants 5 participants 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants 68 participants
Native-Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
  40.0%
2
  20.0%
1
  16.7%
1
  16.7%
2
  33.3%
1
  16.7%
1
  16.7%
10
  14.7%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.5%
White
3
 100.0%
3
 100.0%
1
  50.0%
2
  66.7%
6
 100.0%
2
 100.0%
2
 100.0%
1
  50.0%
3
  60.0%
8
  80.0%
5
  83.3%
5
  83.3%
4
  66.7%
5
  83.3%
5
  83.3%
55
  80.9%
Unknown
0
   0.0%
0
   0.0%
1
  50.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  50.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.9%
1.Primary Outcome
Title Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1
Hide Description An adverse event (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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Time Frame Up to 64 days in Cohort 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population comprised of all randomized participants who received at least one dose of study medication and was based on the actual treatment received, if this differed from that to which the participant was randomized.
Arm/Group Title Part A: Cohort 1: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 orally in one of the Periods of Cohort 1 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 8 6 6 6 5
Measure Type: Count of Participants
Unit of Measure: Participants
Any SAE
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Any non-SAE
3
  37.5%
5
  83.3%
3
  50.0%
2
  33.3%
2
  40.0%
2.Primary Outcome
Title Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2
Hide Description 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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Time Frame Up to 30 days in Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Any SAE
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Any non-SAE
1
  50.0%
0
   0.0%
3
  50.0%
1
  16.7%
3.Primary Outcome
Title Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3
Hide Description 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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Time Frame Up to 30 days in Cohort 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 3: Placebo Part A: Cohort 3: GSK3352589 150 mg Part A: Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 3 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 4 6 5
Measure Type: Count of Participants
Unit of Measure: Participants
Any SAE
0
   0.0%
0
   0.0%
0
   0.0%
Any non-SAE
2
  50.0%
3
  50.0%
1
  20.0%
4.Primary Outcome
Title Part B: Number of Participants With SAEs and Non-SAEs
Hide Description 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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Time Frame Up to 25 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description:
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Any SAE
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Any non-SAE
9
  90.0%
5
  83.3%
6
 100.0%
2
  33.3%
5
  83.3%
5
  83.3%
5.Primary Outcome
Title Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1
Hide Description A complete physical examination will include, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Time Frame Up to 64 days in Cohort 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 1: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 orally in one of the Periods of Cohort 1 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 8 6 6 6 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6.Primary Outcome
Title Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2
Hide Description A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Time Frame Up to 30 days in Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
7.Primary Outcome
Title Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3
Hide Description A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Time Frame Up to 30 days in Cohort 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 3: Placebo Part A: Cohort 3: GSK3352589 150 mg Part A: Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 3 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 4 6 5
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
1
  20.0%
8.Primary Outcome
Title Part B: Number of Participants With Abnormal Findings After Physical Examination
Hide Description A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Time Frame Up to 25 days
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description:
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
9.Primary Outcome
Title Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3
Hide Description Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) findings for ECG parameters have been presented.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
Arm/Group Title Part A: Cohort 1 and 3: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg Part A:Cohort 3: GSK3352589 150 mg Part A:Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 12 6 6 6 5 6 5
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline (Day 1; Pre-dose); Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Baseline (Day 1; Pre-dose); Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 1 Hour Post-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 1 Hour Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 4 Hours Post-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 4 Hours Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 12 Hours Post-dose; Abnormal NCS
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
Day 1; 12 Hours Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 2; Abnormal NCS
1
   8.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
  20.0%
0
   0.0%
0
   0.0%
Day 2; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
10.Primary Outcome
Title Part A: Number of Participants With Abnormal ECG Findings in Cohort 2
Hide Description Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline (Day 1; Pre-dose); Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Baseline; (Day 1;pre dose); Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 1 Hour Post-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 1 Hour Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 4 Hours Post-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 4 Hours Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 12 Hours Post-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 12 Hours Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 2; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 2; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
11.Primary Outcome
Title Part B: Number of Participants With Abnormal ECG Findings
Hide Description Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. 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. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug. The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 7 (Pre-dose, 4 Hours Post-dose), Day 14 (Pre-dose, 4 Hours Post-dose), Follow-up (Day 25)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description:
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline (Day 1; Pre-dose); Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Baseline (Day 1; Pre-dose); Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 1; 4 Hours Post-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
Day 1; 4 Hours Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 7; Pre-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Day 7; Pre-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 7; 4 Hours Post-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 7; 4 Hours Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 14; Pre-dose; Abnormal NCS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 14; Pre-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 14; 4 Hours Post-dose; Abnormal NCS
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Day 14; 4 Hours Post-dose; Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Follow-up (Day 25); Abnormal NCS
1
  10.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
0
   0.0%
Follow-up (Day 25); Abnormal CS
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
12.Primary Outcome
Title Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3
Hide Description Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
Arm/Group Title Part A: Cohort 1 and 3: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg Part A:Cohort 3: GSK3352589 150 mg Part A:Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 12 6 6 6 5 6 5
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury
SBP; Day 1; 1 Hour Post dose -1.25  (9.61) -1.75  (4.71) -2.08  (11.72) 3.00  (9.72) -2.70  (12.26) 1.58  (5.55) -0.10  (3.45)
SBP; Day 1; 4 Hours Post dose -1.29  (11.32) -5.83  (5.86) -1.33  (13.56) 3.75  (11.04) -3.60  (14.72) -1.75  (3.27) 1.40  (1.29)
SBP; Day 1; 12 Hours Post dose 2.21  (8.65) -3.83  (10.11) 1.08  (11.33) 3.00  (10.39) 3.10  (9.15) 1.33  (4.07) 3.90  (6.69)
SBP; Day 2 -2.42  (10.00) -4.50  (5.74) -1.42  (9.77) -2.17  (10.87) -3.40  (7.54) 1.50  (2.53) -5.00  (5.78)
SBP; Day 3 -3.63  (11.05) -8.67  (5.12) -0.42  (16.59) 1.92  (7.05) -3.30  (10.12) 0.67  (4.17) 0.60  (5.90)
DBP; Day 1; 1 Hour Post dose -0.54  (5.62) -0.67  (3.89) 1.75  (4.71) 1.08  (7.34) 1.00  (10.31) 0.33  (4.01) 4.20  (2.59)
DBP; Day 1; 4 Hours Post dose 2.04  (5.87) -0.42  (5.33) -1.83  (5.39) 2.25  (9.95) -2.10  (6.07) 1.17  (4.77) 6.50  (2.06)
DBP; Day 1; 12 Hours Post dose -2.92  (5.67) -4.42  (6.58) -3.08  (5.29) -5.75  (5.33) -4.10  (8.13) -1.08  (5.30) 0.40  (7.99)
DBP; Day 2 -2.13  (4.71) -2.58  (7.91) -2.25  (4.10) -1.17  (4.01) -5.40  (3.44) -0.17  (5.34) 3.60  (4.92)
DBP; Day 3 1.13  (6.30) -2.67  (7.72) 2.67  (5.65) -1.50  (6.43) -2.20  (4.27) 0.75  (4.97) 3.80  (4.91)
13.Primary Outcome
Title Part A: Change From Baseline in SBP and DBP in Cohort 2
Hide Description Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury
SBP; Day 1; 1 Hour Post dose 3.75  (3.89) 6.00  (8.49) 3.75  (9.68) -6.58  (9.91)
SBP; Day 1; 4 Hours Post dose -1.75  (1.06) -6.50  (9.19) -5.17  (11.44) -6.25  (10.30)
SBP; Day 1; 12 Hours Post dose 1.75  (9.55) 10.75  (15.91) 1.50  (10.84) 1.50  (11.66)
SBP; Day 2 -6.75  (5.30) -3.75  (4.60) -7.58  (5.18) -5.00  (9.77)
SBP; Day 3 -0.25  (0.35) 6.75  (10.96) -4.50  (8.06) 1.00  (7.54)
DBP; Day 1; 1 Hour Post dose 1.25  (3.89) -5.75  (2.47) 1.67  (6.23) -4.25  (5.67)
DBP; Day 1; 4 Hours Post dose -3.25  (3.18) -5.00  (3.54) -1.67  (7.10) -4.75  (5.99)
DBP; Day 1; 12 Hours Post dose -5.25  (2.47) -3.00  (2.83) -2.67  (6.92) -6.00  (6.87)
DBP; Day 2 -3.50  (2.12) -5.25  (6.72) -1.92  (4.41) -2.75  (3.49)
DBP; Day 3 1.50  (8.49) 0.75  (7.42) 3.58  (6.94) 2.08  (5.01)
14.Primary Outcome
Title Part B: Change From Baseline in SBP and DBP
Hide Description Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
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Hide Analysis Population Description
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description:
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury
SBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-4.70  (7.00) -1.83  (6.59) -2.33  (6.01) 1.17  (10.69) -2.33  (11.79) -8.08  (7.39)
SBP; Day 2; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-7.35  (5.61) -6.25  (5.37) -5.75  (7.37) -2.33  (13.01) -4.08  (12.69) -9.42  (11.58)
SBP; Day 3; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-5.90  (6.50) -5.25  (13.97) -1.42  (6.42) -9.83  (18.11) -6.83  (11.57) -5.58  (5.24)
SBP; Day 4; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-7.75  (6.91) -5.83  (9.23) 0.83  (8.88) -0.08  (15.46) -9.08  (11.13) -9.42  (6.26)
SBP; Day 5; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-8.55  (8.39) -7.00  (5.85) -1.08  (5.39) -9.33  (18.90) -3.92  (14.39) -11.17  (8.52)
SBP; Day 6; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-9.65  (6.93) -5.33  (8.52) -5.42  (4.25) -6.50  (13.10) -4.08  (16.53) -10.33  (15.03)
SBP; Day 7, Pre-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-7.25  (8.36) -9.75  (6.57) -7.83  (5.85) -7.83  (14.75) -3.50  (10.48) -3.92  (13.91)
SBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-9.00  (5.61) -6.92  (6.50) -6.67  (7.93) -6.92  (10.58) -5.92  (15.81) -7.50  (14.55)
SBP; Day 8; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-8.95  (5.71) -6.00  (9.87) -7.67  (14.50) -4.50  (10.31) -8.00  (9.98) -4.75  (10.01)
SBP; Day 9; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-11.90  (9.74) 0.67  (11.89) -5.83  (5.19) -11.08  (15.23) -8.33  (11.99) -9.00  (13.70)
SBP; Day 10; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-7.15  (7.34) -5.67  (7.15) -1.67  (6.25) -7.67  (15.08) -9.50  (13.57) -15.67  (18.97)
SBP; Day 11; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-8.60  (8.03) -5.00  (9.42) -3.83  (14.31) -7.25  (16.23) -8.42  (10.95) -9.50  (10.31)
SBP; Day 12; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-8.50  (9.06) -5.58  (10.74) -0.08  (10.03) -4.00  (18.10) -9.33  (13.52) -4.25  (12.50)
SBP; Day 13; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-9.15  (7.63) -5.33  (10.30) -1.58  (6.96) -6.67  (17.26) -8.08  (16.69) -6.58  (9.84)
SBP; Day 14, Pre-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-6.90  (9.73) -5.42  (7.64) -0.25  (3.76) -1.83  (15.28) 0.83  (10.93) -9.50  (6.98)
SBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
-5.15  (9.48) -8.50  (8.12) 0.50  (7.13) -13.00  (13.90) -0.25  (13.15) -5.67  (8.64)
SBP; Day 15; n=10,5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
-6.05  (10.20) -1.00  (6.78) 8.08  (8.11) -5.92  (14.17) 2.67  (13.53) -5.42  (8.46)
SBP; Follow-up (Day 25); n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-6.85  (9.32) -4.42  (11.63) -3.67  (7.74) 0.08  (11.00) -1.08  (12.64) -2.83  (7.81)
DBP; Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-4.90  (5.78) -2.17  (5.27) -1.42  (6.92) -2.08  (5.56) -5.00  (7.06) -3.33  (6.77)
DBP; Day 2; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-6.05  (4.83) 1.50  (9.84) -1.67  (5.60) -3.67  (8.22) -3.17  (7.47) -2.25  (8.85)
DBP; Day 3; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-3.30  (5.30) 0.08  (6.64) -2.75  (4.91) -3.50  (6.19) -5.00  (6.54) -2.17  (7.16)
DBP; Day 4; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-7.05  (6.89) -0.58  (10.28) -1.33  (4.54) -3.00  (5.93) -3.33  (2.82) -3.67  (6.68)
DBP; Day 5; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-7.80  (9.26) -1.67  (5.67) -4.17  (3.92) -8.25  (7.90) -3.58  (6.44) -3.33  (9.36)
DBP; Day 6; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-10.20  (7.37) -1.67  (4.83) -3.25  (6.02) -7.25  (5.82) -3.00  (7.54) -6.67  (7.94)
DBP; Day 7, Pre-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-7.20  (7.52) -4.17  (4.67) -6.75  (7.76) -5.17  (5.83) 4.58  (3.99) 0.33  (8.68)
DBP; Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-8.65  (7.04) -3.75  (4.12) -5.92  (4.62) -6.83  (6.12) -2.75  (7.06) -3.67  (10.24)
DBP; Day 8; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-8.20  (6.86) -1.75  (9.42) -5.50  (9.49) -2.75  (8.93) -1.25  (4.47) -4.42  (7.49)
DBP; Day 9; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-10.00  (8.36) -1.08  (8.67) -3.08  (4.19) -8.00  (9.17) -6.75  (7.13) -4.42  (6.73)
DBP; Day 10; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-5.35  (8.93) 1.50  (4.71) -3.00  (7.22) -5.25  (6.26) -2.42  (8.75) -6.50  (12.08)
DBP; Day 11; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-6.80  (10.14) -1.25  (8.60) -4.58  (7.37) -6.25  (7.01) -5.08  (4.73) -3.92  (7.21)
DBP; Day 12; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-6.95  (5.44) -2.67  (8.65) -1.42  (4.44) -5.42  (7.81) -2.00  (3.79) -0.50  (7.62)
DBP; Day 13; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-7.55  (8.26) -1.42  (10.70) -2.50  (5.13) -2.92  (8.23) -1.08  (5.70) -2.67  (8.17)
DBP; Day 14, Pre-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-6.10  (7.05) -4.25  (6.19) 0.17  (5.69) -3.58  (5.10) 2.67  (3.66) -0.83  (7.77)
DBP; Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
-6.65  (7.12) -6.80  (8.25) -3.58  (4.87) -8.83  (7.45) 5.00  (5.68) 0.33  (8.85)
DBP; Day 15; n=10,5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
-6.75  (10.22) 1.30  (7.13) 2.00  (7.47) -5.67  (6.47) 2.00  (8.40) -4.08  (7.28)
DBP; Follow-up (Day 25); n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-5.85  (8.87) -3.92  (7.56) -1.75  (5.10) -1.75  (8.62) 1.00  (5.06) -1.17  (10.63)
15.Primary Outcome
Title Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3
Hide Description Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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Hide Analysis Population Description
Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
Arm/Group Title Part A: Cohort 1 and 3: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg Part A:Cohort 3: GSK3352589 150 mg Part A:Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 12 6 6 6 5 6 5
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Day 1; 1 Hour Post dose -3.79  (6.30) -3.25  (4.39) -3.00  (6.66) -3.25  (6.93) -4.00  (7.44) -2.75  (5.69) -3.20  (5.38)
Day 1; 4 Hours Post dose -6.42  (5.91) -4.92  (5.98) -4.67  (6.59) -0.75  (7.96) -6.90  (5.03) -3.67  (4.70) -3.40  (3.17)
Day 1; 12 Hours Post dose 2.38  (6.34) 0.75  (3.40) 5.83  (6.04) 6.00  (3.10) 0.40  (8.93) 2.33  (3.88) 2.40  (6.44)
Day 2 -1.46  (9.11) -3.33  (7.77) -2.42  (6.90) 2.08  (4.57) -3.60  (7.21) -2.83  (2.14) -1.60  (3.60)
Day 3 0.54  (7.17) -0.08  (10.84) -1.75  (9.49) 0.50  (7.06) -2.50  (10.62) -2.08  (5.44) 0.50  (5.15)
16.Primary Outcome
Title Part A: Change From Baseline in Pulse Rate in Cohort 2
Hide Description Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Day 1; 1 Hour Post dose 1.50  (1.41) 7.50  (0.71) 0.42  (4.98) 9.08  (4.33)
Day 1; 4 Hours Post dose 1.75  (2.47) -1.00  (2.12) -1.33  (3.87) 2.75  (3.95)
Day 1; 12 Hours Post dose 7.00  (2.12) 9.25  (0.35) 9.33  (3.42) 7.92  (2.76)
Day 2 1.25  (3.89) 3.00  (4.24) 4.33  (4.74) 3.17  (5.39)
Day 3 8.00  (4.95) 4.75  (3.18) 6.92  (7.12) 7.58  (8.29)
17.Primary Outcome
Title Part B: Change From Baseline in Pulse Rate
Hide Description Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description:
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-1.55  (4.75) -0.42  (8.65) -2.25  (4.16) -3.58  (4.90) -1.17  (7.13) -3.42  (5.74)
Day 2; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
3.35  (7.07) 2.50  (10.80) -0.25  (5.52) 0.50  (8.63) -2.67  (7.28) 0.08  (6.41)
Day 3; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
4.85  (4.53) 3.33  (7.05) 0.58  (5.62) 1.08  (8.34) -6.92  (8.45) -2.25  (5.35)
Day 4; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
3.25  (8.47) 2.42  (10.53) -1.67  (3.80) 1.33  (9.10) 2.58  (9.16) -0.17  (6.77)
Day 5; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.25  (6.03) -1.17  (9.03) 2.75  (6.83) 1.92  (9.09) -0.25  (9.96) 3.92  (10.11)
Day 6; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.50  (5.33) 5.42  (11.74) -0.33  (8.94) -1.33  (8.24) 0.08  (9.04) -2.67  (8.05)
Day 7, Pre-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-1.55  (5.23) 0.25  (8.30) -0.25  (10.24) -0.75  (5.66) 0.50  (9.44) -0.25  (5.40)
Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.20  (4.82) 3.75  (10.14) -5.08  (5.38) -0.58  (5.52) -1.25  (7.29) 1.17  (6.63)
Day 8; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.55  (7.37) 1.42  (9.06) 1.42  (6.15) 2.08  (7.28) -0.17  (10.75) 5.83  (6.93)
Day 9; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
1.05  (8.59) 2.58  (7.01) 0.83  (5.91) 2.50  (5.59) -4.42  (12.73) 2.67  (10.35)
Day 10; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.10  (5.64) -1.83  (10.52) -4.33  (5.82) -0.25  (7.62) -3.33  (8.30) -2.17  (7.82)
Day 11; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
1.45  (7.98) -2.58  (10.12) -1.75  (6.33) 0.00  (6.75) 0.42  (12.46) -3.58  (7.01)
Day 12; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.50  (5.48) -1.17  (12.30) -2.33  (8.68) 0.17  (4.69) 1.75  (10.11) 3.25  (11.02)
Day 13; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
2.45  (5.83) 2.00  (9.70) -0.08  (8.63) 2.92  (11.59) -2.25  (11.49) -2.08  (9.58)
Day 14, Pre-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-2.35  (3.93) 0.25  (10.12) -1.50  (10.11) -2.17  (7.81) -0.17  (7.75) 0.42  (4.89)
Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
0.40  (5.00) 0.90  (11.06) -5.75  (4.26) -2.58  (7.39) 3.83  (9.11) -0.08  (6.67)
Day 15; n=10,5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
0.85  (4.34) 4.00  (5.28) 6.17  (9.68) 4.00  (6.57) 5.58  (8.03) 7.67  (6.05)
Follow-up (Day 25); n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
6.25  (8.77) 0.00  (6.67) 4.25  (4.41) 10.58  (8.44) 5.83  (13.14) 6.92  (6.85)
18.Primary Outcome
Title Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3
Hide Description Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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Hide Analysis Population Description
Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
Arm/Group Title Part A: Cohort 1 and 3: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg Part A:Cohort 3: GSK3352589 150 mg Part A:Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 12 6 6 6 5 6 5
Mean (Standard Deviation)
Unit of Measure: Celsius
Day 1; 1 Hour Post dose -0.09  (0.29) 0.00  (0.00) -0.22  (0.43) -0.15  (0.31) -0.12  (0.34) 0.00  (0.00) -0.20  (0.24)
Day 1; 4 Hours Post dose -0.09  (0.29) 0.00  (0.00) -0.22  (0.43) -0.15  (0.31) -0.12  (0.34) 0.00  (0.00) -0.20  (0.24)
Day 1; 12 Hours Post dose -0.09  (0.29) 0.00  (0.00) -0.22  (0.43) -0.15  (0.31) -0.12  (0.34) 0.00  (0.00) -0.20  (0.24)
Day 2 -0.04  (0.38) -0.13  (0.37) -0.27  (0.28) -0.30  (0.42) -0.58  (0.30) -0.22  (0.29) 0.00  (0.25)
Day 3 -0.07  (0.41) -0.18  (0.26) -0.45  (0.58) 0.00  (0.49) -0.16  (0.59) 0.10  (0.48) 0.26  (0.48)
19.Primary Outcome
Title Part A: Change From Baseline in Body Temperature in Cohort 2
Hide Description Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
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Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Mean (Standard Deviation)
Unit of Measure: Celsius
Day 1; 1 Hour Post dose 0.00  (0.00) -0.10  (0.00) 0.00  (0.00) 0.00  (0.47)
Day 1; 4 Hours Post dose 0.00  (0.00) -0.10  (0.00) 0.00  (0.00) 0.00  (0.47)
Day 1; 12 Hours Post dose 0.00  (0.00) -0.10  (0.00) 0.00  (0.00) 0.00  (0.47)
Day 2 -0.15  (0.07) -0.15  (0.21) -0.33  (0.73) 0.03  (0.39)
Day 3 -0.20  (0.14) -0.35  (0.07) -0.10  (0.49) -0.22  (0.56)
20.Primary Outcome
Title Part B: Change From Baseline in Body Temperature
Hide Description Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description:
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Celsius
Day 1; 4 Hours Post dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.00  (0.00) 0.00  (0.00) 0.00  (0.00) 0.00  (0.00) 0.00  (0.00) 0.00  (0.00)
Day 2; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.05  (0.32) -0.03  (0.37) 0.05  (0.30) -0.02  (0.43) 0.13  (0.47) -0.20  (0.39)
Day 3; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.09  (0.55) -0.10  (0.15) 0.05  (0.49) 0.45  (0.33) 0.13  (0.52) 0.03  (0.42)
Day 4; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.07  (0.31) -0.10  (0.36) -0.07  (0.49) 0.05  (0.20) 0.07  (0.35) 0.03  (0.36)
Day 5; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.16  (0.32) 0.18  (0.13) 0.23  (0.38) 0.05  (0.21) 0.27  (0.38) -0.45  (0.38)
Day 6; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.17  (0.51) 0.33  (0.28) -0.05  (0.48) 0.53  (0.21) 0.13  (0.57) 0.05  (0.49)
Day 7, Pre-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.18  (0.45) 0.12  (0.30) 0.08  (0.38) 0.23  (0.18) 0.02  (0.29) -0.08  (0.42)
Day 7, 4 Hours Post-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.18  (0.45) 0.12  (0.30) 0.08  (0.38) 0.23  (0.18) 0.02  (0.29) -0.08  (0.42)
Day 8; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.17  (0.34) -0.02  (0.34) 0.40  (0.37) 0.08  (0.56) 0.02  (0.54) -0.15  (0.61)
Day 9; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.08  (0.40) 0.15  (0.32) 0.30  (0.23) 0.15  (0.39) 0.23  (0.45) -0.20  (0.62)
Day 10; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.07  (0.51) 0.17  (0.26) 0.08  (0.45) -0.10  (0.49) -0.48  (0.60) -0.02  (0.32)
Day 11; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.05  (0.47) 0.05  (0.39) -0.02  (0.38) 0.07  (0.42) 0.00  (0.50) -0.02  (0.39)
Day 12; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.04  (0.67) 0.00  (0.39) -0.23  (0.45) 0.55  (0.26) -0.07  (0.45) -0.08  (0.41)
Day 13; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.07  (0.42) 0.03  (0.37) 0.15  (0.48) -0.08  (0.18) 0.05  (0.38) -0.12  (0.40)
Day 14, Pre-dose; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.17  (0.45) 0.48  (0.31) 0.27  (0.44) 0.25  (0.31) -0.10  (0.31) -0.12  (0.48)
Day 14, 4 Hours Post-dose; n=10,5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
0.17  (0.45) 0.42  (0.29) 0.27  (0.44) 0.25  (0.31) -0.10  (0.31) -0.12  (0.48)
Day 15; n=10,5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
0.27  (0.35) 0.10  (0.24) 0.47  (0.46) 0.30  (0.55) 0.28  (0.47) 0.03  (0.31)
Follow-up (Day 25); n=10,6,5,6,6,6 Number Analyzed 10 participants 6 participants 5 participants 6 participants 6 participants 6 participants
0.18  (0.58) 0.17  (0.52) 0.24  (0.61) 0.68  (0.34) 0.47  (0.32) 0.08  (0.36)
21.Primary Outcome
Title Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1
Hide Description The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Time Frame Up to 64 days in Cohort 1
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 1: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 orally in one of the Periods of Cohort 1 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 8 6 6 6 5
Measure Type: Count of Participants
Unit of Measure: Participants
Type 1
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Type 2
3
  37.5%
3
  50.0%
2
  33.3%
0
   0.0%
0
   0.0%
Type 3
3
  37.5%
1
  16.7%
2
  33.3%
3
  50.0%
1
  20.0%
Type 4
1
  12.5%
1
  16.7%
2
  33.3%
1
  16.7%
3
  60.0%
Type 5
4
  50.0%
3
  50.0%
2
  33.3%
3
  50.0%
1
  20.0%
Type 6
3
  37.5%
0
   0.0%
2
  33.3%
2
  33.3%
1
  20.0%
Type 7
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
0
   0.0%
22.Primary Outcome
Title Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2
Hide Description The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Time Frame Up to 30 days in Cohort 2
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Measure Type: Count of Participants
Unit of Measure: Participants
Type 1
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Type 2
0
   0.0%
0
   0.0%
3
  50.0%
1
  16.7%
Type 3
1
  50.0%
1
  50.0%
2
  33.3%
3
  50.0%
Type 4
1
  50.0%
1
  50.0%
3
  50.0%
1
  16.7%
Type 5
0
   0.0%
0
   0.0%
1
  16.7%
0
   0.0%
Type 6
0
   0.0%
0
   0.0%
0
   0.0%
1
  16.7%
Type 7
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
23.Primary Outcome
Title Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3
Hide Description The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Time Frame Up to 30 days in Cohort 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 3: Placebo Part A: Cohort 3: GSK3352589 150 mg Part A: Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 3 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 4 6 5
Measure Type: Count of Participants
Unit of Measure: Participants
Type 1
0
   0.0%
0
   0.0%
1
  20.0%
Type 2
0
   0.0%
1
  16.7%
0
   0.0%
Type 3
2
  50.0%
4
  66.7%
3
  60.0%
Type 4
2
  50.0%
5
  83.3%
5
 100.0%
Type 5
0
   0.0%
3
  50.0%
2
  40.0%
Type 6
1
  25.0%
0
   0.0%
0
   0.0%
Type 7
0
   0.0%
0
   0.0%
0
   0.0%
24.Primary Outcome
Title Part B: Average BSFS at Indicated Time Points
Hide Description The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Time Frame Day -1, Days 1-3, Days 4-7, Days 1-7, Days 8-14
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description:
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Day -1; n=7,4, 6,6,4,5 Number Analyzed 7 participants 4 participants 6 participants 6 participants 4 participants 5 participants
3.17  (1.30) 3.88  (0.63) 3.92  (0.49) 3.92  (1.43) 4.13  (1.03) 4.30  (0.84)
Days 1-3; n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
3.93  (1.14) 3.55  (1.57) 3.97  (1.06) 3.62  (0.71) 3.75  (1.33) 3.37  (0.91)
Days 4-7;n=9,6,6,6,6,6 Number Analyzed 9 participants 6 participants 6 participants 6 participants 6 participants 6 participants
4.32  (1.14) 3.78  (1.30) 3.68  (1.14) 3.37  (0.47) 3.85  (0.95) 3.45  (0.34)
Days 1-7;n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
4.14  (0.99) 3.75  (1.36) 3.77  (0.86) 3.48  (0.50) 3.78  (1.08) 3.38  (0.34)
Days 8-14;n=10,6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
4.12  (0.97) 3.63  (1.12) 3.93  (0.77) 3.10  (0.63) 3.63  (1.29) 3.48  (0.48)
25.Primary Outcome
Title Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3
Hide Description Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Day -1) and Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
Arm/Group Title Part A: Cohort 1 and 3: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg Part A:Cohort 3: GSK3352589 150 mg Part A:Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 12 6 6 6 5 6 5
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter
Basophils; Day 3 0.01  (0.05) 0.00  (0.06) 0.02  (0.04) 0.00  (0.06) 0.04  (0.05) -0.03  (0.05) -0.05  (0.05)
Eosinophils; Day 3 0.02  (0.06) 0.02  (0.08) 0.05  (0.14) -0.03  (0.05) 0.02  (0.05) 0.02  (0.04) 0.04  (0.05)
Lymphocytes; Day 3 -0.37  (0.40) -0.10  (0.40) -0.32  (0.46) -0.43  (0.36) -0.50  (0.34) 0.03  (0.31) -0.16  (0.29)
Monocytes; Day 3 -0.05  (0.12) -0.08  (0.10) -0.13  (0.08) -0.08  (0.12) -0.04  (0.21) 0.03  (0.08) 0.02  (0.04)
Neutrophils; Day 3 -0.66  (1.05) -0.73  (1.06) -0.60  (1.55) -0.23  (0.70) -0.16  (2.76) -0.60  (0.85) -0.36  (0.90)
Platelets; Day 3 -15.0  (34.6) -4.8  (34.1) -22.5  (45.6) 2.2  (32.4) -8.0  (43.7) -23.3  (13.9) -46.6  (36.5)
Leukocytes ;Day 3 -1.01  (1.06) -0.88  (0.95) -0.95  (1.33) -0.82  (0.80) -0.58  (2.64) -0.53  (0.94) -0.52  (0.94)
26.Primary Outcome
Title Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2
Hide Description Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Day -1) and Day 3
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Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter
Basophils; Day 3 0.00  (0.00) 0.00  (0.00) 0.00  (0.00) 0.02  (0.04)
Eosinophils; Day 3 0.05  (0.08) 0.05  (0.07) 0.00  (0.06) 0.03  (0.06)
Lymphocytes; Day 3 0.10  (0.14) 0.10  (0.14) 0.25  (0.65) 0.12  (0.58)
Monocytes; Day 3 -0.05  (0.07) -0.05  (0.07) -0.02  (0.15) -0.08  (0.10)
Neutrophils; Day 3 -1.00  (0.42) -0.85  (0.35) -1.25  (1.97) -1.73  (1.84)
Platelets; Day 3 -7.0  (11.3) -45.0  (26.9) -7.2  (5.9) -29.2  (27.0)
Leukocytes ;Day 3 -0.90  (0.57) -0.75  (0.35) -1.00  (2.44) -1.68  (2.30)
27.Primary Outcome
Title Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes
Hide Description Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID
Hide Arm/Group Description:
Participants received repeat doses of placebo BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 5 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 15 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 50 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 100 mg BID administered for 14 days in Part B of the study.
Participants received repeat doses of GSK3352589 200 mg BID administered for 14 days in Part B of the study.
Overall Number of Participants Analyzed 10 6 6 6 6 6
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter
Basophils; Day 7;n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.03  (0.06) 0.00  (0.06) 0.05  (0.05) 0.03  (0.05) 0.02  (0.04) 0.02  (0.04)
Basophils; Day 15;n=10, 5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
0.03  (0.06) 0.04  (0.05) 0.05  (0.05) 0.05  (0.05) 0.03  (0.05) 0.02  (0.04)
Basophils; Follow-up (Day 25) ; n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.05  (0.05) 0.00  (0.06) 0.06  (0.05) 0.05  (0.05) 0.02  (0.07) 0.00  (0.00)
Eosinophils; Day 7;n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.01  (0.09) 0.03  (0.05) -0.02  (0.04) 0.03  (0.08) 0.05  (0.05) 0.04  (0.08)
Eosinophils, Day 15;n=10, 5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
0.02  (0.10) 0.04  (0.11) 0.02  (0.04) 0.03  (0.08) 0.05  (0.05) -0.03  (0.08)
Eosinophils; Follow-up (Day 25); n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.01  (0.09) 0.05  (0.09) 0.04  (0.05) 0.03  (0.10) 0.05  (0.08) -0.03  (0.11)
Lymphocytes; Day 7 ;n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.09  (0.35) -0.35  (0.26) -0.18  (0.24) -0.10  (0.30) 0.23  (0.19) -0.22  (0.40)
Lymphocytes; Day 15; n=10, 5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
0.04  (0.32) 0.02  (0.22) 0.10  (0.20) -0.05  (0.36) 0.40  (0.25) -0.10  (0.19)
Lymphocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
0.14  (0.25) -0.12  (0.33) 0.25  (0.35) 0.00  (0.13) 0.07  (0.23) -0.32  (0.17)
Monocytes; Day 7;n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.03  (0.09) -0.03  (0.05) -0.08  (0.12) -0.10  (0.06) 0.05  (0.10) 0.02  (0.08)
Monocytes; Day 15;n=10, 5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
-0.09  (0.11) -0.02  (0.04) -0.02  (0.08) -0.10  (0.09) 0.05  (0.05) -0.07  (0.08)
Monocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.04  (0.12) -0.05  (0.10) 0.03  (0.08) -0.10  (0.06) 0.17  (0.27) -0.07  (0.10)
Neutrophils; Day 7;n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.08  (1.05) 0.05  (0.57) -0.42  (0.34) -0.65  (0.98) -0.82  (0.79) -0.88  (0.57)
Neutrophils; Day 15;n=10, 5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
-0.31  (0.74) -0.02  (0.39) -0.22  (0.77) -0.72  (0.87) -0.58  (0.50) -0.95  (0.75)
Neutrophils; Follow-up (Day 25); n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.55  (0.94) 0.05  (0.42) 0.07  (0.66) -0.37  (1.33) 0.73  (3.34) -0.58  (1.05)
Platelets; Day 7;n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
10.4  (25.0) 9.7  (21.9) 8.3  (20.8) 26.7  (12.1) -11.0  (12.1) 4.5  (21.1)
Platelets; Day 15;n=10, 5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
12.3  (28.5) 24.2  (26.7) -3.0  (23.9) 3.7  (16.6) 7.3  (25.5) 7.5  (21.3)
Platelets; Follow-up (Day 25); n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
17.5  (34.5) 37.3  (24.3) 26.2  (24.2) 27.3  (37.0) 2.5  (20.9) 2.5  (9.0)
Leukocytes; Day 7;n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.18  (1.13) -0.32  (0.52) -0.65  (0.60) -0.82  (1.00) -0.53  (0.92) -1.08  (0.67)
Leukocytes ;Day 15;n=10, 5,6,6,6,6 Number Analyzed 10 participants 5 participants 6 participants 6 participants 6 participants 6 participants
-0.32  (0.79) 0.10  (0.47) -0.13  (0.76) -0.82  (0.85) -0.08  (0.45) -1.10  (0.62)
Leukocytes; Follow-up (Day 25); n=10, 6,6,6,6,6 Number Analyzed 10 participants 6 participants 6 participants 6 participants 6 participants 6 participants
-0.39  (0.72) -0.12  (0.59) 0.43  (0.88) -0.45  (1.24) 0.98  (3.38) -1.00  (1.01)
28.Primary Outcome
Title Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3
Hide Description Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Day -1) and Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. In Cohort 1 and 3, participants were dosed in similar single ascending doses, cross-over sequences. Hence, combined totals for placebo arm is presented as pre-specified in protocol and reporting and analysis plan.
Arm/Group Title Part A: Cohort 1 and 3: Placebo Part A: Cohort 1: GSK3352589 2 mg Part A: Cohort 1: GSK3352589 5 mg Part A: Cohort 1: GSK3352589 15 mg Part A: Cohort 1: GSK3352589 50 mg Part A:Cohort 3: GSK3352589 150 mg Part A:Cohort 3: GSK3352589 400 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 in one of the Periods of Cohort 1 and Cohort 3 in Part A of the study.
Participants received GSK3352589 2 mg tablet orally in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 5 mg tablet orally in Period 2 of Cohort 1 in Part A of the study.
Participants received GSK3352589 15 mg tablet orally in Period 3 of Cohort 1 in Part A of the study.
Participants received GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study.
Participants received GSK3352589 150 mg tablet in Period 1 of Cohort 3 in Part A of the study.
Participants received GSK3352589 400 mg tablet in Period 2 of Cohort 3 in Part A of the study.
Overall Number of Participants Analyzed 12 6 6 6 5 6 5
Mean (Standard Deviation)
Unit of Measure: 10^12 cells per liter
0.029  (0.260) 0.275  (0.321) -0.073  (0.310) 0.112  (0.390) 0.120  (0.373) 0.063  (0.094) -0.132  (0.132)
29.Primary Outcome
Title Part A: Change From Baseline in Erythrocytes in Cohort 2
Hide Description Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Day -1) and Day 3
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Part A: Cohort 2: Fasted Placebo Part A: Cohort 2: Fed Placebo Part A: Cohort 2: GSK3352589 Fasted 25 mg Part A: Cohort 2: GSK3352589 Fed 25 mg
Hide Arm/Group Description:
Participants received placebo tablet matching GSK3352589 without food in Period 1 of Cohort 2 in Part A of the study.
Participants received placebo tablet matching GSK3352589 with food in Period 2 of Cohort 2 in Part A of the study.
Participants received GSK3352589 25 mg tablet without food in Period 1 of Cohort 1 in Part A of the study.
Participants received GSK3352589 25 mg tablet with food in Period 2 of Cohort 1 in Part A of the study.
Overall Number of Participants Analyzed 2 2 6 6
Mean (Standard Deviation)
Unit of Measure: 10^12 cells per liter
0.110  (0.156) 0.150  (0.269) 0.167  (0.118) 0.042  (0.157)
30.Primary Outcome
Title Part B: Change From Baseline in Erythrocytes
Hide Description Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Time Frame Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population. Only those participants with data available at specified time point were analyzed (reported by n=X in category titles).
Arm/Group Title Part B: Placebo BID Part B: GSK3352589 5 mg BID Part B: GSK3352589 15 mg BID Part B: GSK3352589 50 mg BID Part B: GSK3352589 100 mg BID Part B: GSK3352589 200 mg BID