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Dose Escalation and Dose Expansion Study of GSK525762 in Combination With Androgen Deprivation Therapy in Participants With Castrate-resistant Prostate Cancer

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ClinicalTrials.gov Identifier: NCT03150056
Recruitment Status : Terminated (This study has been terminated due to meeting protocol defined futility.)
First Posted : May 11, 2017
Results First Posted : August 26, 2021
Last Update Posted : August 10, 2022
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Tumours
Interventions Drug: GSK525762
Drug: Abiraterone
Drug: Enzalutamide
Drug: Prednisone
Enrollment 73
Recruitment Details This was an open-label, dose escalation and expansion study to investigate safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in combination with abiraterone or enzalutamide in participants with castrate resistant prostate cancer (CRPC).
Pre-assignment Details This study has been terminated due to meeting protocol defined futility. A total of 73 participants were enrolled in the study.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months. Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months. Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Period Title: Overall Study
Started 10 6 4 10 22 21
Completed 0 1 1 2 9 3
Not Completed 10 5 3 8 13 18
Reason Not Completed
Withdrawal by Subject             0             0             0             0             0             2
Study terminated by Sponsor             1             3             1             1             5             6
Death             9             2             2             7             8             10
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg Total
Hide Arm/Group Description Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months. Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months. Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Total of all reporting groups
Overall Number of Baseline Participants 10 6 4 10 22 21 73
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants 6 participants 4 participants 10 participants 22 participants 21 participants 73 participants
70.4  (7.69) 68.0  (9.57) 76.3  (4.11) 69.3  (4.72) 71.0  (6.49) 69.1  (5.11) 70.2  (6.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 6 participants 4 participants 10 participants 22 participants 21 participants 73 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
10
 100.0%
6
 100.0%
4
 100.0%
10
 100.0%
22
 100.0%
21
 100.0%
73
 100.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 6 participants 4 participants 10 participants 22 participants 21 participants 73 participants
Asian-East Asian Heritage
2
  20.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.7%
Black or African American
1
  10.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.5%
1
   4.8%
3
   4.1%
White-Arabic/North African Heritage
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   4.8%
1
   1.4%
White-White/Caucasian/European Heritage
7
  70.0%
6
 100.0%
4
 100.0%
10
 100.0%
21
  95.5%
19
  90.5%
67
  91.8%
1.Primary Outcome
Title Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgement, or is associated with liver injury and impaired liver function.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population consisted of all participants who received at least one dose of GSK525762 or abiraterone or enzalutamide.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
Any AEs
10
 100.0%
6
 100.0%
4
 100.0%
10
 100.0%
22
 100.0%
21
 100.0%
Any SAEs
4
  40.0%
2
  33.3%
0
   0.0%
1
  10.0%
6
  27.3%
7
  33.3%
2.Primary Outcome
Title Number of Participants With AEs Leading to Any Dose Reduction or Delays
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to any dose reduction or delays have been presented.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
Dose reduction
4
  40.0%
1
  16.7%
0
   0.0%
7
  70.0%
10
  45.5%
7
  33.3%
Dose delay
5
  50.0%
2
  33.3%
4
 100.0%
8
  80.0%
15
  68.2%
12
  57.1%
3.Primary Outcome
Title Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment
Hide Description Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs have been presented.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
6
  60.0%
2
  33.3%
2
  50.0%
3
  30.0%
8
  36.4%
4
  19.0%
4.Primary Outcome
Title Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50)
Hide Description PSA50 response rate is defined as percentage of participants with a decrease of >=50% in the PSA concentration from the Baseline PSA value determined at least 12 weeks after start of treatment and confirmed >=4 weeks later by an additional PSA evaluation.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population comprised of all participants who received at least one dose of GSK525762 plus abiraterone/enzalutamide. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 19 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0.0 to 30.8)
0
(0.0 to 45.9)
0
(0.0 to 60.2)
0
(0.0 to 30.8)
0
(0.0 to 17.6)
0
(0.0 to 16.1)
5.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246
Hide Description Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK525762 and GSK3529246 (metabolite of GSK525762). PK parameters were calculated using standard non-compartmental analysis. PK Population consisted of all participants from the All Treated Safety Population for whom a PK sample was obtained and analyzed.
Time Frame Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 21 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
GSK525762:Week1 Day1,n=10,6,4,10,21,18 Number Analyzed 10 participants 6 participants 4 participants 10 participants 21 participants 18 participants
950.319
(19.18%)
993.154
(33.77%)
671.129
(30.44%)
427.580
(31.76%)
333.256
(48.86%)
336.296
(43.28%)
GSK525762:Week3 Day1,n=4,3,3,9,17,10 Number Analyzed 4 participants 3 participants 3 participants 9 participants 17 participants 10 participants
891.302
(36.79%)
735.171
(21.63%)
559.711
(40.59%)
284.298
(45.12%)
158.409
(153.45%)
171.527
(47.88%)
GSK3529246:Week1 Day1,n=10,6,4,10,21,18 Number Analyzed 10 participants 6 participants 4 participants 10 participants 21 participants 18 participants
280.892
(43.14%)
318.772
(31.13%)
199.456
(32.94%)
408.208
(39.86%)
321.750
(24.24%)
323.685
(25.77%)
GSK3529246:Week3 Day1,n=4,3,3,10,17,10 Number Analyzed 4 participants 3 participants 3 participants 10 participants 17 participants 10 participants
447.929
(39.30%)
444.232
(26.74%)
364.151
(15.46%)
449.614
(49.54%)
328.398
(39.74%)
356.615
(18.26%)
6.Secondary Outcome
Title Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246
Hide Description Blood samples were collected at indicated time points for PK analysis of GSK525762 and GSK3529246 (metabolite of GSK525762). PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 21 18
Median (Full Range)
Unit of Measure: Hours
GSK525762:Week1 Day1,n=10,6,4,10,21,18 Number Analyzed 10 participants 6 participants 4 participants 10 participants 21 participants 18 participants
0.800
(0.50 to 2.92)
0.558
(0.50 to 1.00)
1.000
(0.58 to 3.08)
0.508
(0.40 to 1.08)
1.000
(0.45 to 3.00)
0.742
(0.50 to 6.00)
GSK525762:Week3 Day1,n=4,3,3,9,17,10 Number Analyzed 4 participants 3 participants 3 participants 9 participants 17 participants 10 participants
0.500
(0.50 to 0.50)
1.000
(0.50 to 3.00)
0.950
(0.50 to 1.00)
0.583
(0.47 to 3.00)
0.933
(0.00 to 3.03)
0.517
(0.50 to 3.08)
GSK3529246:Week1 Day1,n=10,6,4,10,21,18 Number Analyzed 10 participants 6 participants 4 participants 10 participants 21 participants 18 participants
3.000
(1.18 to 6.00)
3.000
(0.53 to 6.00)
2.042
(1.00 to 3.08)
2.067
(1.00 to 3.00)
2.917
(0.53 to 6.05)
1.817
(0.95 to 6.00)
GSK3529246:Week3 Day1,n=4,3,3,10,17,10 Number Analyzed 4 participants 3 participants 3 participants 10 participants 17 participants 10 participants
1.000
(0.85 to 3.00)
3.000
(1.00 to 6.17)
3.000
(1.00 to 3.03)
1.042
(0.50 to 6.00)
1.017
(0.00 to 6.00)
1.875
(0.50 to 6.33)
7.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval (AUC[0-tau]) of GSK525762 and Its Active Metabolites GSK3529246
Hide Description Blood samples were collected at indicated time points for PK analysis of GSK525762 and GSK3529246 (metabolite of GSK525762). PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 8 2 3 6 12 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*nanogram per milliliter
GSK525762:Week1 Day1,n=8,2,2,6,9,8 Number Analyzed 8 participants 2 participants 2 participants 6 participants 9 participants 8 participants
4927.834
(71.78%)
4677.411
(21.59%)
4172.282
(31.08%)
1139.481
(34.32%)
1261.529
(102.14%)
959.452
(60.97%)
GSK525762:Week3 Day1,n=4,1,3,5,6,6 Number Analyzed 4 participants 1 participants 3 participants 5 participants 6 participants 6 participants
2697.923
(69.10%)
2580.877 [1] 
(NA%)
1561.908
(13.67%)
674.437
(57.10%)
660.607
(14.41%)
386.950
(37.03%)
GSK3529246:Week1 Day1,n=2,1,0,5,9,10 Number Analyzed 2 participants 1 participants 0 participants 5 participants 9 participants 10 participants
3765.196
(0.47%)
4918.549 [1] 
(NA%)
4379.342
(30.76%)
3373.990
(19.73%)
3306.018
(31.84%)
GSK3529246:Week3 Day1,n=2,2,2,4,12,7 Number Analyzed 2 participants 2 participants 2 participants 4 participants 12 participants 7 participants
4170.516
(6.55%)
5146.749
(9.99%)
4598.235
(16.28%)
3816.407
(37.02%)
3386.702
(30.44%)
3082.516
(33.36%)
[1]
Geometric coefficient of variation could not be calculated for a single participant.
8.Secondary Outcome
Title Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246
Hide Description Blood samples were collected at indicated time points for PK analysis of GSK525762 and GSK3529246 (metabolite of GSK525762). PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 8 3 3 9 20 17
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
GSK525762:Week1 Day1,n=8,2,3,1,3,4 Number Analyzed 8 participants 2 participants 3 participants 1 participants 3 participants 4 participants
22.418
(192.37%)
8.696
(72.93%)
13.664
(119.83%)
2.100 [1] 
(NA%)
5.053
(3035.92%)
1.660
(34.60%)
GSK525762:Week3 Day1,n=2,2,2,1,0,0 Number Analyzed 2 participants 2 participants 2 participants 1 participants 0 participants 0 participants
8.966
(93.46%)
4.555
(522.90%)
1.410
(48.34%)
3.540 [1] 
(NA%)
GSK3529246:Week1 Day1,n=8,3,3,9,20,17 Number Analyzed 8 participants 3 participants 3 participants 9 participants 20 participants 17 participants
58.995
(52.50%)
68.379
(47.51%)
42.107
(52.26%)
46.011
(38.73%)
37.765
(56.41%)
38.200
(53.15%)
GSK3529246:Week3 Day1,n=3,3,2,7,13,8 Number Analyzed 3 participants 3 participants 2 participants 7 participants 13 participants 8 participants
48.223
(99.09%)
48.291
(29.86%)
63.526
(3.90%)
50.882
(77.10%)
32.299
(60.18%)
26.165
(76.95%)
[1]
Geometric coefficient of variation could not be calculated for a single participant.
9.Secondary Outcome
Title Cmax of Abiraterone
Hide Description Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Overall Number of Participants Analyzed 10 5 4
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
Week 1 Day 1, n=10,5,4 Number Analyzed 10 participants 5 participants 4 participants
77.962
(57.07%)
63.369
(114.31%)
122.496
(131.30%)
Week 3 Day 1, n=4,4,2 Number Analyzed 4 participants 4 participants 2 participants
149.673
(65.39%)
87.554
(110.92%)
146.924
(76.98%)
10.Secondary Outcome
Title Tmax of Abiraterone
Hide Description Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Overall Number of Participants Analyzed 10 5 4
Median (Full Range)
Unit of Measure: Hours
Week 1 Day 1, n=10,5,4 Number Analyzed 10 participants 5 participants 4 participants
1.133
(0.17 to 3.13)
1.083
(0.53 to 3.00)
0.750
(0.00 to 1.08)
Week 3 Day 1, n=4,4,2 Number Analyzed 4 participants 4 participants 2 participants
1.000
(0.85 to 1.00)
2.000
(0.98 to 3.00)
3.017
(3.00 to 3.03)
11.Secondary Outcome
Title AUC(0-tau) of Abiraterone
Hide Description Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Overall Number of Participants Analyzed 5 2 1
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*nanogram per milliliter
Week 1 Day 1, n=5,1,1 Number Analyzed 5 participants 1 participants 1 participants
432.368
(56.74%)
148.871 [1] 
(NA%)
1405.809 [1] 
(NA%)
Week 3 Day 1, n=1,2,1 Number Analyzed 1 participants 2 participants 1 participants
1361.627 [1] 
(NA%)
595.686
(64.72%)
2185.039 [1] 
(NA%)
[1]
Geometric coefficient of variation could not be calculated for a single participant.
12.Secondary Outcome
Title Ctrough of Abiraterone
Hide Description Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Overall Number of Participants Analyzed 9 4 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanogram per milliliter
Week 1 Day 1, n=9,2,3 Number Analyzed 9 participants 2 participants 3 participants
7.603
(93.00%)
4.636
(1802.64%)
11.263
(86.21%)
Week 3 Day 1, n=2,4,1 Number Analyzed 2 participants 4 participants 1 participants
15.114
(9.84%)
7.697
(69.99%)
21.800 [1] 
(NA%)
[1]
Geometric coefficient of variation could not be calculated for a single participant.
13.Secondary Outcome
Title Cmax of Enzalutamide
Hide Description Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Cmax could not be derived as only pre-dose samples were collected.
Arm/Group Title GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 22 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Microgram per milliliter
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
[1]
Cmax could not be derived as only pre-dose samples were collected.
14.Secondary Outcome
Title Tmax of Enzalutamide
Hide Description Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Tmax could not be derived as only pre-dose samples were collected.
Arm/Group Title GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 22 21
Median (Full Range)
Unit of Measure: Hours
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Tmax could not be derived as only pre-dose samples were collected.
15.Secondary Outcome
Title AUC(0-tau) of Enzalutamide
Hide Description Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. AUC(0-tau) could not be derived as only pre-dose samples were collected.
Arm/Group Title GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 22 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Hours*microgram per milliliter
NA [1] 
(NA%)
NA [1] 
(NA%)
NA [1] 
(NA%)
[1]
AUC(0-tau) could not be derived as only pre-dose samples were collected
16.Secondary Outcome
Title Ctrough of Enzalutamide
Hide Description Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis.
Time Frame Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 20 18
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Microgram per milliliter
Week 1 Day 1, Pre-dose, n=9,20,18 Number Analyzed 9 participants 20 participants 18 participants
13.066
(21.74%)
13.313
(21.70%)
14.546
(30.34%)
Week 3 Day 1, Pre-dose, n=9,19,13 Number Analyzed 9 participants 19 participants 13 participants
10.385
(23.30%)
10.902
(24.96%)
11.497
(27.34%)
Week 5 Day 1, Pre-dose, n=10,15,18 Number Analyzed 10 participants 15 participants 18 participants
10.026
(21.80%)
9.814
(44.21%)
12.561
(31.27%)
Week 9 Day 1, Pre-dose, n=6,6,13 Number Analyzed 6 participants 6 participants 13 participants
10.021
(27.01%)
8.064
(85.90%)
12.056
(30.12%)
Week 17 Day 1, Pre-dose, n=4,2,4 Number Analyzed 4 participants 2 participants 4 participants
8.621
(22.86%)
12.568
(10.14%)
10.267
(58.45%)
Week 25 Day 1, Pre-dose, n=2,2,2 Number Analyzed 2 participants 2 participants 2 participants
10.103
(8.13%)
13.069
(9.75%)
13.791
(5.13%)
17.Secondary Outcome
Title Disease Control Rate at Week 24
Hide Description Disease control rate (DCR) is defined as the percentage of participants with >=1 post-Baseline disease assessment who showed either a confirmed complete response (CR), partial response (PR) or stable disease (SD) observed at >=24 weeks per prostate cancer working group 3 (PCWG3)-modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; where CR: disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeter in the short axis; PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters; SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive diseases. Confidence interval (CI) was computed using exact two sided 95% CI.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 9 5 4 10 19 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0.0 to 33.6)
40
(5.3 to 85.3)
50
(6.8 to 93.2)
40
(12.2 to 73.8)
11
(1.3 to 33.1)
29
(11.3 to 52.2)
18.Secondary Outcome
Title Composite Response Rate
Hide Description Composite response rate was defined as the percentage of participants with one of the following: a) Response based on PCWG3-modified RECIST version 1.1, b) PSA decrease of >=50% from Baseline at Week 12 and thereafter, or c) Circulating Tumor-cell Count Conversion from unfavorable (>=5/7.5 milliliter [mL]) at Baseline to favorable (<5/7.5 mL) confirmed by a second assessment at least 4 weeks later. If a participant met at least one of the above requirements, then that participant was considered a composite responder. CI was computed using exact two sided 95% CI.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0.0 to 30.8)
0
(0.0 to 45.9)
0
(0.0 to 60.2)
10
(0.3 to 44.5)
5
(0.1 to 22.8)
0
(0.0 to 16.1)
19.Secondary Outcome
Title Objective Response Rate
Hide Description Objective response rate (ORR) is defined as the percentage of participants with a confirmed CR or PR at any time as per PCWG3-modified RECIST version 1.1; where CR: Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeter (mm) in the short axis and PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 9 5 4 10 19 21
Measure Type: Number
Unit of Measure: Percentage of participants
0 0 0 0 0 0
20.Secondary Outcome
Title Circulating Tumor Cells (CTC) Response Rate
Hide Description CTC response rate is defined as the percentage of participants with a CTC conversion to <5/7.5 mL blood at nadir (confirmed by a second consecutive value obtained four or more weeks later) for participants with unfavourable CTC (>=5/7.5 mL) at Baseline. CI was computed using exact two sided 95% CI.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed. For GSK525762 40 mg+Abiraterone 1000 mg arm, there were no unfavorable values at Baseline, hence CTC response rate (change from unfavorable to favorable) could not be derived for this arm.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 7 3 0 3 12 11
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0.0 to 41.0)
0
(0.0 to 70.8)
33
(0.8 to 90.6)
8
(0.2 to 38.5)
0
(0.0 to 28.5)
21.Secondary Outcome
Title Prostate-specific Antigen (PSA) Response Rate at Week 4
Hide Description PSA Response Rate is defined as percentage of participants achieving >=30% decrease from Baseline PSA after 4 weeks of study treatment. The CI was calculated using exact two sided 95% CI for the percentage of participants with Baseline PSA values who show >=30% reduction in PSA at >=4 weeks post-Baseline.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
0
(0.0 to 30.8)
17
(0.4 to 64.1)
0
(0.0 to 60.2)
0
(0.0 to 30.8)
0
(0.0 to 17.6)
0
(0.0 to 16.1)
22.Secondary Outcome
Title Time to Disease Progression
Hide Description Time to disease progression is defined as the time from date of first dose of study treatment to date of disease progression defined as one or more of the following criteria: 1. Radiographic progression by PCWG3-modified RECIST version 1.1 for participants with measurable disease, 2. Bone progression on bone scan according to the PCGW3 criteria, 3. PSA progression according to the PCWG3 criteria accompanied by any one of the following: investigator-defined clinical progression or either of the above RECIST version 1.1 radiographic progression or bone progression.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Median (Inter-Quartile Range)
Unit of Measure: Days
88.0
(36.0 to 88.0)
NA [1] 
(86.0 to NA)
NA [1] 
(36.0 to NA)
87.0
(85.0 to 112.0)
86.0 [2] 
(56.0 to NA)
84.0
(52.0 to 330.0)
[1]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
[2]
<75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
23.Secondary Outcome
Title Radiographic Progression-free Survival (rPFS)
Hide Description rPFS is defined as the time from study treatment start until the first date of either disease progression or death due to any cause. The date of disease progression is defined as the earliest date of disease progression as assessed by the investigator using PCWG3-modified RECIST, version 1.1 or progression on bone scan. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time Frame Up to 21.3 montths
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Median (Inter-Quartile Range)
Unit of Measure: Days
53.0
(29.5 to 165.0)
NA [1] 
(NA to NA)
NA [2] 
(36.0 to NA)
416.0
(165.0 to 421.0)
141.0
(56.0 to 220.0)
330.0
(52.0 to 333.0)
[1]
<25% of participants experienced the event within the treatment arm. Hence, median and inter-quartile range could not be derived.
[2]
<50% of participants experienced the event within the treatment arm. Hence, median and third-quartile could not be derived.
24.Secondary Outcome
Title Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status
Hide Description Performance status assessments were based on 6-point ECOG scale (from 0 to 5), where 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work); 2=ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed or chair; and 5=dead. Data for worst case post-Baseline is presented.
Time Frame Up to 21.3 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 21 21
Measure Type: Count of Participants
Unit of Measure: Participants
0
2
  20.0%
0
   0.0%
0
   0.0%
2
  20.0%
1
   4.8%
1
   4.8%
1
7
  70.0%
4
  66.7%
3
  75.0%
5
  50.0%
16
  76.2%
13
  61.9%
2
1
  10.0%
2
  33.3%
0
   0.0%
3
  30.0%
3
  14.3%
6
  28.6%
3
0
   0.0%
0
   0.0%
1
  25.0%
0
   0.0%
1
   4.8%
1
   4.8%
4
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
5
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
25.Secondary Outcome
Title Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30): Global Health Status (GHS)
Hide Description EORTC QLQ-C30 includes 30-items with single and multi-item scales. These included 5 functional scales (physical functioning, role functioning, cognitive functioning, emotional functioning and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/ Quality-of-Life (QoL) scale, and six single items (constipation, diarrhea, insomnia, dyspnea, appetite loss and financial difficulties). Response options for GHS/QoL range from 1 to 4, where 1=not at all and 4=very much. Scores were averaged and transformed to a 0 to 100 scale, with higher scores representing a high QoL. Baseline is defined as the latest non-missing assessment time-point prior to the first study treatment dose. Change from Baseline was calculated as post-Baseline visit value minus Baseline value.
Time Frame Baseline (Week 1 Day 1, pre-dose) and on Day 1 of Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 61
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 6 1 2 4 6 10
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 1 Day 1,n=1,0,0,0,2,0 Number Analyzed 1 participants 0 participants 0 participants 0 participants 2 participants 0 participants
8.3 [1]   (NA) 4.2  (5.89)
Week 2 Day 1,n=6,1,2,4,4,8 Number Analyzed 6 participants 1 participants 2 participants 4 participants 4 participants 8 participants
-8.3  (12.91) 16.7 [1]   (NA) -12.5  (29.46) -2.1  (4.17) 0.0  (13.61) -1.0  (12.94)
Week 3 Day 1,n=6,0,1,4,3,7 Number Analyzed 6 participants 0 participants 1 participants 4 participants 3 participants 7 participants
-8.3  (23.57) -16.7 [1]   (NA) -4.2  (8.33) 2.8  (4.81) -1.2  (3.15)
Week 4 Day 1,n=6,1,2,3,6,10 Number Analyzed 6 participants 1 participants 2 participants 3 participants 6 participants 10 participants
-8.3  (10.54) 16.7 [1]   (NA) 0.0  (11.79) 5.6  (9.62) 1.4  (9.74) 2.5  (16.22)
Week 5 Day 1,n=3,0,1,3,5,9 Number Analyzed 3 participants 0 participants 1 participants 3 participants 5 participants 9 participants
-8.3  (14.43) 8.3 [1]   (NA) -5.6  (9.62) 0.0  (11.79) -0.0  (11.02)
Week 9 Day 1,n=2,0,1,2,3,6 Number Analyzed 2 participants 0 participants 1 participants 2 participants 3 participants 6 participants
-12.5  (17.68) -8.3 [1]   (NA) -20.8  (5.89) -30.6  (12.73) -12.5  (10.21)
Week 13 Day 1,n=1,1,1,1,2,3 Number Analyzed 1 participants 1 participants 1 participants 1 participants 2 participants 3 participants
-25.0 [1]   (NA) 8.3 [1]   (NA) 0.0 [1]   (NA) 0.0 [1]   (NA) -8.3  (11.79) 0.0  (0.00)
Week 17 Day 1,n=1,1,1,1,1,3 Number Analyzed 1 participants 1 participants 1 participants 1 participants 1 participants 3 participants
-25.0 [1]   (NA) -16.7 [1]   (NA) 16.7 [1]   (NA) 0.0 [1]   (NA) 0.0 [1]   (NA) -11.1  (19.25)
Week 21 Day 1,n=0,0,1,1,0,2 Number Analyzed 0 participants 0 participants 1 participants 1 participants 0 participants 2 participants
16.7 [1]   (NA) 0.0 [1]   (NA) -4.2  (5.89)
Week 25 Day 1,n=0,0,1,0,0,1 Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 1 participants
0.0 [1]   (NA) -8.3 [1]   (NA)
Week 29 Day 1,n=0,0,0,0,0,2 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 2 participants
-8.3  (11.79)
Week 33 Day 1,n=0,0,1,0,1,2 Number Analyzed 0 participants 0 participants 1 participants 0 participants 1 participants 2 participants
8.3 [1]   (NA) 0.0 [1]   (NA) -8.3  (11.79)
Week 37 Day 1,n=0,0,1,0,0,3 Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 3 participants
0.0 [1]   (NA) -2.8  (4.81)
Week 41 Day 1,n=0,0,1,0,0,0 Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 0 participants
8.3 [1]   (NA)
Week 45 Day 1,n=0,0,1,0,0,1 Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 1 participants
-8.3 [1]   (NA) 0.0 [1]   (NA)
Week 49 Day 1,n=0,0,1,0,0,2 Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 2 participants
16.7 [1]   (NA) -8.3  (0.00)
Week 61 Day 1,n=0,0,1,0,0,1 Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 1 participants
16.7 [1]   (NA) -16.7 [1]   (NA)
[1]
Standard deviation could not be calculated for single participant.
26.Secondary Outcome
Title Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours
Hide Description BPI-SF is 9-item self-administered questionnaire. Pain intensity score was calculated from the four items (items 3, 4, 5 and 6) for worst pain, least pain, average pain and current pain. Worst pain in last 24 hours was rated from 0 (no pain) to 10 (pain as bad as you can imagine). Baseline is defined as the latest non-missing assessment time-point prior to the first study treatment dose (latest up to Week 1 Day 1). Change from Baseline was calculated as post-Baseline visit value minus Baseline value.
Time Frame Baseline (Pre-dose on Week 1 Day 1) and on Day 1 of Weeks 2, 3, 4, 5, 9, 13, 17, 21, 25, 29, 33, 37, 41, 45, 49, 61, 73, 85, 97
Hide Outcome Measure Data
Hide Analysis Population Description
Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 9 5 4 10 19 17
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 2 Day 1,n=9,5,4,9,14,13 Number Analyzed 9 participants 5 participants 4 participants 9 participants 14 participants 13 participants
0.1  (2.62) 0.8  (2.86) -2.3  (1.71) 0.0  (1.12) 0.0  (2.91) 0.2  (1.48)
Week 3 Day 1,n=8,3,4,10,16,15 Number Analyzed 8 participants 3 participants 4 participants 10 participants 16 participants 15 participants
0.5  (1.77) -1.7  (1.53) -1.8  (1.89) -1.0  (2.05) 0.3  (3.26) 0.0  (1.51)
Week 4 Day 1,n=8,4,3,8,16,15 Number Analyzed 8 participants 4 participants 3 participants 8 participants 16 participants 15 participants
0.4  (1.92) 0.5  (1.91) -1.3  (1.15) -0.8  (1.28) 0.2  (2.81) 0.4  (1.76)
Week 5 Day 1,n=6,4,4,10,19,17 Number Analyzed 6 participants 4 participants 4 participants 10 participants 19 participants 17 participants
-0.8  (3.06) -0.3  (1.26) -1.0  (0.82) -0.9  (2.13) 0.7  (3.38) -0.2  (1.78)
Week 9 Day 1,n=3,4,3,8,10,13 Number Analyzed 3 participants 4 participants 3 participants 8 participants 10 participants 13 participants
1.3  (1.53) 1.3  (0.96) -0.3  (2.52) -0.5  (2.07) 0.2  (2.49) -0.4  (2.40)
Week 13 Day 1,n=2,3,1,5,7,7 Number Analyzed 2 participants 3 participants 1 participants 5 participants 7 participants 7 participants
0.5  (0.71) 2.0  (3.00) 2.0 [1]   (NA) 0.2  (1.92) -1.7  (2.21) -0.4  (2.15)
Week 17 Day 1,n=2,4,2,5,3,8 Number Analyzed 2 participants 4 participants 2 participants 5 participants 3 participants 8 participants
2.5  (7.78) 3.5  (4.36) -0.5  (4.95) -0.8  (3.11) -1.3  (1.15) -0.5  (2.20)
Week 21 Day 1,n=1,2,2,5,3,6 Number Analyzed 1 participants 2 participants 2 participants 5 participants 3 participants 6 participants
2.0 [1]   (NA) 0.5  (0.71) -2.5  (0.71) -0.2  (2.49) -2.3  (4.04) 1.0  (1.79)
Week 25 Day 1,n=0,0,1,2,3,4 Number Analyzed 0 participants 0 participants 1 participants 2 participants 3 participants 4 participants
3.0 [1]   (NA) 0.0  (0.00) -1.3  (5.69) -1.0  (1.15)
Week 29 Day 1,n=0,0,1,3,2,4 Number Analyzed 0 participants 0 participants 1 participants 3 participants 2 participants 4 participants
-3.0 [1]   (NA) -0.7  (1.15) -3.5  (0.71) 0.8  (4.19)
Week 33 Day 1,n=0,0,1,3,2,2 Number Analyzed 0 participants 0 participants 1 participants 3 participants 2 participants 2 participants
1.0 [1]   (NA) 0.7  (1.15) -1.5  (2.12) -1.0  (1.41)
Week 37 Day 1,n=0,0,1,3,0,4 Number Analyzed 0 participants 0 participants 1 participants 3 participants 0 participants 4 participants
0.0 [1]   (NA) 1.7  (2.08) 0.0  (1.41)
Week 41 Day 1,n=0,0,1,3,1,1 Number Analyzed 0 participants 0 participants 1 participants 3 participants 1 participants 1 participants
-1.0 [1]   (NA) 1.3  (1.53) -3.0 [1]   (NA) -1.0 [1]   (NA)
Week 45 Day 1,n=0,0,1,2,1,3 Number Analyzed 0 participants 0 participants 1 participants 2 participants 1 participants 3 participants
1.0 [1]   (NA) 2.5  (2.12) -1.0 [1]   (NA) 1.7  (1.15)
Week 49 Day 1,n=0,0,1,3,1,3 Number Analyzed 0 participants 0 participants 1 participants 3 participants 1 participants 3 participants
2.0 [1]   (NA) 0.3  (1.53) -3.0 [1]   (NA) 2.7  (2.52)
Week 61 Day 1,n=0,0,1,1,1,1 Number Analyzed 0 participants 0 participants 1 participants 1 participants 1 participants 1 participants
-2.0 [1]   (NA) 0.0 [1]   (NA) -3.0 [1]   (NA) 3.0 [1]   (NA)
Week 73 Day 1,n=0,0,0,1,1,0 Number Analyzed 0 participants 0 participants 0 participants 1 participants 1 participants 0 participants
0.0 [1]   (NA) -2.0 [1]   (NA)
Week 85 Day 1,n=0,0,0,1,1,0 Number Analyzed 0 participants 0 participants 0 participants 1 participants 1 participants 0 participants
3.0 [1]   (NA) -3.0 [1]   (NA)
Week 97 Day 1,n=0,0,0,0,1,0 Number Analyzed 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
-3.0 [1]   (NA)
[1]
Standard deviation could not be calculated for single participant.
27.Other Pre-specified Outcome
Title Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgement, or is associated with liver injury and impaired liver function. Number of Participants With any AEs and SAEs collected from start of the treatment until end of the study were reported.
Time Frame Up to 3 years and 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
Any AEs
10
 100.0%
6
 100.0%
4
 100.0%
10
 100.0%
22
 100.0%
21
 100.0%
Any SAEs
4
  40.0%
2
  33.3%
0
   0.0%
1
  10.0%
6
  27.3%
7
  33.3%
28.Other Pre-specified Outcome
Title Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of Participants with AEs leading to any dose reduction or delays from start of the treatment until end of the study were reported.
Time Frame Up to 3 years and 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
Dose reduction
4
  40.0%
1
  16.7%
0
   0.0%
7
  70.0%
10
  45.5%
7
  33.3%
Dose delay
5
  50.0%
2
  33.3%
4
 100.0%
8
  80.0%
15
  68.2%
12
  57.1%
29.Other Pre-specified Outcome
Title Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study
Hide Description Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs from start of the treatment until end of the study were reported.
Time Frame Up to 3 years and 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
All Treated Population
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description:
Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label.
Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
Overall Number of Participants Analyzed 10 6 4 10 22 21
Measure Type: Count of Participants
Unit of Measure: Participants
6
  60.0%
2
  33.3%
2
  50.0%
3
  30.0%
8
  36.4%
4
  19.0%
Time Frame All-cause mortality, non-serious adverse events (non-SAEs) and serious adverse events (SAEs) were collected up to 3 years and 11 months
Adverse Event Reporting Description All-cause mortality, non-SAES and SAEs were assessed using All Treated Population which consisted of all participants who received at least one dose of GSK525762 or abiraterone or enzalutamide.
 
Arm/Group Title GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Hide Arm/Group Description Participants received once daily oral dose of GSK525762 60 milligram (mg) in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received an alternate dosing schedule- once daily GSK525762 60 mg + abiraterone 1000 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received once daily oral dose of GSK525762 40 mg in combination with abiraterone 1000 mg up to maximum of 21.3 months. Participants received prednisone 5 mg orally twice daily as per abiraterone label. Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months. Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months. Participants received an alternate dosing schedule- once daily GSK525762 60 mg + enzalutamide 160 mg tablets via the oral route for 2 weeks followed by 1 week off-treatment up to maximum of 21.3 months.
All-Cause Mortality
GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/10 (90.00%)      2/6 (33.33%)      2/4 (50.00%)      7/10 (70.00%)      8/22 (36.36%)      10/21 (47.62%)    
Hide Serious Adverse Events
GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/10 (40.00%)      2/6 (33.33%)      0/4 (0.00%)      1/10 (10.00%)      6/22 (27.27%)      7/21 (33.33%)    
Blood and lymphatic system disorders             
Disseminated intravascular coagulation † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Thrombocytopenia † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Cardiac disorders             
Myocarditis † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Gastrointestinal disorders             
Diarrhoea † 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Gastric haemorrhage † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Nausea † 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Rectal haemorrhage † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Vomiting † 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
General disorders             
Fatigue † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Infections and infestations             
Myelitis † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Pneumonia † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Urinary tract infection † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Injury, poisoning and procedural complications             
Clavicle fracture † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Femur fracture † 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Subdural haemorrhage † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 1/10 (10.00%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Metabolism and nutrition disorders             
Dehydration † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Hypercalcaemia † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Musculoskeletal and connective tissue disorders             
Back pain † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Pathological fracture † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Spinal osteoarthritis † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Nervous system disorders             
Intraventricular haemorrhage † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Paraplegia † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Renal and urinary disorders             
Acute kidney injury † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 1/21 (4.76%)  1
Haematuria † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 1/21 (4.76%)  1
Renal impairment † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 0/22 (0.00%)  0 0/21 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Epistaxis † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
Skin and subcutaneous tissue disorders             
Rash † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
1
Term from vocabulary, MedDRA 23.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
GSK525762 60 mg+Abiraterone 1000 mg GSK525762 60 mg Alternate+Abiraterone 1000 mg GSK525762 40 mg+Abiraterone 1000 mg GSK525762 80 mg+Enzalutamide 160 mg GSK525762 60 mg+Enzalutamide 160 mg GSK525762 60 mg Alternate+Enzalutamide 160 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/10 (100.00%)      6/6 (100.00%)      4/4 (100.00%)      10/10 (100.00%)      22/22 (100.00%)      21/21 (100.00%)    
Blood and lymphatic system disorders             
Anaemia † 1  4/10 (40.00%)  4 2/6 (33.33%)  2 0/4 (0.00%)  0 3/10 (30.00%)  4 7/22 (31.82%)  8 3/21 (14.29%)  3
Thrombocytopenia † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 1/4 (25.00%)  1 3/10 (30.00%)  4 9/22 (40.91%)  14 4/21 (19.05%)  6
Gastrointestinal disorders             
Nausea † 1  7/10 (70.00%)  9 3/6 (50.00%)  3 1/4 (25.00%)  2 6/10 (60.00%)  7 8/22 (36.36%)  9 11/21 (52.38%)  17
Diarrhoea † 1  3/10 (30.00%)  3 2/6 (33.33%)  2 2/4 (50.00%)  5 2/10 (20.00%)  3 6/22 (27.27%)  10 7/21 (33.33%)  10
Vomiting † 1  5/10 (50.00%)  6 1/6 (16.67%)  1 0/4 (0.00%)  0 2/10 (20.00%)  2 6/22 (27.27%)  11 7/21 (33.33%)  10
Constipation † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 3/10 (30.00%)  3 1/22 (4.55%)  2 2/21 (9.52%)  2
Abdominal pain † 1  2/10 (20.00%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0 2/10 (20.00%)  2 1/22 (4.55%)  1 0/21 (0.00%)  0
Dry mouth † 1  2/10 (20.00%)  2 1/6 (16.67%)  1 0/4 (0.00%)  0 0/10 (0.00%)  0 1/22 (4.55%)  1 0/21 (0.00%)  0
General disorders             
Fatigue † 1  7/10 (70.00%)  8 2/6 (33.33%)  2 0/4 (0.00%)  0 3/10 (30.00%)  3 11/22 (50.00%)  18 7/21 (33.33%)  9
Asthenia † 1  0/10 (0.00%)  0 3/6 (50.00%)  4 4/4 (100.00%)  5 2/10 (20.00%)  7 8/22 (36.36%)  11 11/21 (52.38%)  14
Infections and infestations             
Urinary tract infection † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0 1/10 (10.00%)  1 2/22 (9.09%)  2 0/21 (0.00%)  0
Investigations             
Platelet count decreased † 1  4/10 (40.00%)  6 2/6 (33.33%)  5 1/4 (25.00%)  1 4/10 (40.00%)  17 4/22 (18.18%)  5 4/21 (19.05%)  8
Amylase increased † 1  3/10 (30.00%)  3 0/6 (0.00%)  0 2/4 (50.00%)  3 2/10 (20.00%)  3 1/22 (4.55%)  1 2/21 (9.52%)  2
International normalised ratio increased † 1  1/10 (10.00%)  1 1/6 (16.67%)  1 1/4 (25.00%)  1 2/10 (20.00%)  2 0/22 (0.00%)  0 1/21 (4.76%)  1
Blood alkaline phosphatase increased † 1  1/10 (10.00%)  1 1/6 (16.67%)  1 0/4 (0.00%)  0 1/10 (10.00%)  1 1/22 (4.55%)  1 1/21 (4.76%)  1
Blood bilirubin increased † 1  2/10 (20.00%)  2 0/6 (0.00%)  0 1/4 (25.00%)  1 1/10 (10.00%)  1 1/22 (4.55%)  1 0/21 (0.00%)  0
Lipase increased † 1  1/10 (10.00%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0 3/10 (30.00%)  7 0/22 (0.00%)  0 1/21 (4.76%)  1
Blood creatinine increased † 1  1/10 (10.00%)  2 1/6 (16.67%)  1 0/4 (0.00%)  0 0/10 (0.00%)  0 2/22 (9.09%)  2 0/21 (0.00%)  0
Troponin I increased † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 0/10 (0.00%)  0 3/22 (13.64%)  3 1/21 (4.76%)  1
Weight decreased † 1  2/10 (20.00%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0 1/10 (10.00%)  1 0/22 (0.00%)  0 1/21 (4.76%)  1
Metabolism and nutrition disorders             
Decreased appetite † 1  4/10 (40.00%)  4 4/6 (66.67%)  4 4/4 (100.00%)  6 4/10 (40.00%)  6 9/22 (40.91%)  15 13/21 (61.90%)  15
Hyperglycaemia † 1  4/10 (40.00%)  5 3/6 (50.00%)  4 0/4 (0.00%)  0 4/10 (40.00%)  5 0/22 (0.00%)  0 4/21 (19.05%)  6
Hypertriglyceridaemia † 1  2/10 (20.00%)  2 1/6 (16.67%)  2 0/4 (0.00%)  0 1/10 (10.00%)  1 1/22 (4.55%)  1 1/21 (4.76%)  1
Hypokalaemia † 1  4/10 (40.00%)  4 0/6 (0.00%)  0 0/4 (0.00%)  0 1/10 (10.00%)  1 0/22 (0.00%)  0 0/21 (0.00%)  0
Musculoskeletal and connective tissue disorders             
Back pain † 1  2/10 (20.00%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0 4/10 (40.00%)  4 3/22 (13.64%)  4 6/21 (28.57%)  7
Arthralgia † 1  0/10 (0.00%)  0 1/6 (16.67%)  1 2/4 (50.00%)  2 3/10 (30.00%)  3 4/22 (18.18%)  4 4/21 (19.05%)  5
Bone pain † 1  0/10 (0.00%)  0 1/6 (16.67%)  1 0/4 (0.00%)  0 0/10 (0.00%)  0 2/22 (9.09%)  2 3/21 (14.29%)  3
Pain in extremity † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 3/10 (30.00%)  3 0/22 (0.00%)  0 3/21 (14.29%)  3
Nervous system disorders             
Dysgeusia † 1  5/10 (50.00%)  7 2/6 (33.33%)  2 2/4 (50.00%)  3 2/10 (20.00%)  5 7/22 (31.82%)  11 10/21 (47.62%)  11
Dizziness † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 1/4 (25.00%)  1 4/10 (40.00%)  5 3/22 (13.64%)  3 3/21 (14.29%)  4
Headache † 1  2/10 (20.00%)  2 1/6 (16.67%)  1 0/4 (0.00%)  0 1/10 (10.00%)  1 3/22 (13.64%)  4 2/21 (9.52%)  2
Renal and urinary disorders             
Haematuria † 1  1/10 (10.00%)  1 0/6 (0.00%)  0 0/4 (0.00%)  0 1/10 (10.00%)  1 1/22 (4.55%)  1 2/21 (9.52%)  3
Respiratory, thoracic and mediastinal disorders             
Epistaxis † 1  3/10 (30.00%)  4 0/6 (0.00%)  0 0/4 (0.00%)  0 4/10 (40.00%)  4 3/22 (13.64%)  3 4/21 (19.05%)  5
Cough † 1  2/10 (20.00%)  2 0/6 (0.00%)  0 0/4 (0.00%)  0 2/10 (20.00%)  2 2/22 (9.09%)  2 3/21 (14.29%)  3
Dyspnoea † 1  3/10 (30.00%)  3 1/6 (16.67%)  1 0/4 (0.00%)  0 0/10 (0.00%)  0 2/22 (9.09%)  2 2/21 (9.52%)  4
Skin and subcutaneous tissue disorders             
Rash † 1  0/10 (0.00%)  0 1/6 (16.67%)  1 1/4 (25.00%)  1 2/10 (20.00%)  3 3/22 (13.64%)  4 2/21 (9.52%)  3
Pruritus † 1  1/10 (10.00%)  1 1/6 (16.67%)  1 1/4 (25.00%)  1 1/10 (10.00%)  2 2/22 (9.09%)  3 1/21 (4.76%)  1
Dry skin † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 0/4 (0.00%)  0 2/10 (20.00%)  2 0/22 (0.00%)  0 2/21 (9.52%)  2
Vascular disorders             
Hypertension † 1  1/10 (10.00%)  2 0/6 (0.00%)  0 1/4 (25.00%)  1 1/10 (10.00%)  1 1/22 (4.55%)  1 1/21 (4.76%)  1
Haematoma † 1  0/10 (0.00%)  0 0/6 (0.00%)  0 1/4 (25.00%)  2 0/10 (0.00%)  0 1/22 (4.55%)  1 2/21 (9.52%)  2
1
Term from vocabulary, MedDRA 23.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03150056    
Other Study ID Numbers: 204697
2016-003416-13 ( EudraCT Number )
First Submitted: May 9, 2017
First Posted: May 11, 2017
Results First Submitted: July 29, 2021
Results First Posted: August 26, 2021
Last Update Posted: August 10, 2022