Dose Escalation and Dose Expansion Study of GSK525762 in... | NCT03150056

ID	Type	Description	Link
2016-003416-13	EudraCT Number

Label	Type	Description	Intervention Names
GSK525762 + Abiraterone (+ Prednisone) (Arm A)	Experimental		Drug: GSK525762 Drug: Abiraterone Drug: Prednisone
GSK525762 + Enzalutamide (Arm B)	Experimental		Drug: GSK525762 Drug: Enzalutamide

Name	Type	Description	Arm Group Labels	Other Names
GSK525762	Drug	GSK525762 will be administered.	GSK525762 + Abiraterone (+ Prednisone) (Arm A) GSK525762 + Enzalutamide (Arm B)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Up to 21.3 months
Number of Participants With AEs Leading to Any Dose Reduction or Delays	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.	Up to 21.3 months
Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment	Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs have been presented.	Up to 21.3 months
Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50)	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.	Up to 21.3 months

Secondary Outcomes

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246	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.

Other Outcomes

Measure	Description	Time Frame
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Written informed consent provided.
Males >=18 years of age (at the time written consent is obtained for screening).
Histologically confirmed adenocarcinoma of the prostate: screening and on-treatment biopsy is mandatory. If adequate number of paired biopsy samples are collected (>=20 paired samples for each dose level in each Arm, unless an Arm is closed early), then further biopsy sampling will be considered based on available data; screening biopsy can be waived if participant had a recent biopsy after failure of the most recent therapy (within 30 days) and the biopsy sample is secured to be sent as screening biopsy for this study.
Surgically or medically castrated, with testosterone levels of less than or equal to (<=)50 nanograms per deciliter (ng/dL) (<2.0 nanometer [nM]). If the participant is being treated with luteinizing hormone-releasing hormone (LHRH) agonists/antagonists (participant who have not undergone orchiectomy) this therapy must have been initiated at least 4 weeks prior to Week 1 Day 1 and must be continued throughout the study.
Participants must have failed prior therapy with abiraterone, enzalutamide, or both:
1. Has completed at least 12 weeks of prior continuous therapy with abiraterone or enzalutamide in any prior line.
2. Lead-in dosing period for enzalutamide only will be required under the following circumstance:
(i) If the participant has enzalutamide discontinuation for >7 days prior to dosing start with GSK525762 plus enzalutamide on trial, then a enzalutamide only lead-in dosing of 28 days is required.

(ii) If the participant has enzalutamide discontinuation for <=7 days prior to dosing start with GSK525762 plus enzalutamide on trial, then an enzalutamide only lead-in dosing of 14 days is required.

(iii) If the participant is on continuous dosing with enzalutamide prior to dosing start with GSK525762 plus enzalutamide on trial, then participant can start on combined dosing at end of screening period.

(c) Lead-in dosing period for abiraterone only will be required: if the participant has abiraterone discontinuation for more than 3 days prior to dosing start with GSK525762 plus abiraterone on trial, then abiraterone only lead-in dosing of 7 days is required.

One to two line(s) of prior taxane-based chemotherapy allowed. If docetaxel chemotherapy is used more than once, this will be considered as one regimen. Participants who have not received prior chemotherapy in any setting will qualify for study if they are ineligible for or refuse chemotherapy.
Documented prostate cancer progression as assessed by the investigator with one of the following:
1. PSA progression defined by a minimum of 3 rising PSA levels with an interval of >=1 week between each determination. The PSA value at screening must be >=5 microgram (µg)/Liter (L) (5 ng/mL) if PSA is the only indication of progression; participants on systemic glucocorticoids for control of symptoms must have documented PSA progression by PCWG3 while on systemic glucocorticoids prior to commencing Week 1 Day 1 treatment.
2. Radiographic progression of soft tissue disease by PCWG3-modified RECIST 1.1 criteria or bone metastasis with 2 or more documented new bone lesions on a bone scan with or without PSA progression.
ECOG performance status of 0 or 1.
Life expectancy >12 weeks.
Able to swallow and retain orally administered medication.
Must have adequate organ function.
Male participants are eligible to participate if they agree to use contraceptive methods.

Exclusion Criteria:

Surgery or local prostatic intervention (excluding a prostatic biopsy) less than 28 days of Week 1 Day 1.
Participants with neuroendocrine and/or small cell CRPC.
Recent prior therapy, defined as:
1. Any investigational or approved non-biologic anti-cancer drug within 14 days prior to the first dose of GSK525762 and abiraterone/enzalutamide.
2. Any nitrosoureas or mitomycin C within 42 days prior to the first dose of GSK525762 and abiraterone/enzalutamide.
3. Any anti-cancer biologic agents within five half-lives prior to the first dose of GSK525762 and abiraterone/enzalutamide.
4. If the participant received radiotherapy <90 days prior to study treatment, the irradiated lesion cannot be the only lesion used for evaluating response.
5. Any major surgery within 28 days prior to the first dose of GSK525762 and abiraterone/enzalutamide.
Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, cardiac disease, or clinically significant bleeding episodes). Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric disorder, or other conditions that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator; systolic blood pressure higher than 150 millimeter of mercury (mmHg) or diastolic blood pressure higher than 90 mmHg found on 2 separate occasions separated by 1 week, despite adequate therapy, will be defined as uncontrolled hypertension; uncontrolled diabetes mellitus (despite therapeutic, compliance intervention) as defined by a hemoglobin A1c (HbA1c) level more than 8% and/or occurrence of more than 2 episodes of ketoacidosis in the 12 months prior to the first dose of study drug.
Cardiac abnormalities as evidenced by any of the following:
1. Baseline QT interval corrected for heart rate by Fridericia's formula (QTcF) interval >=480 milliseconds (msec).
2. Clinically significant conduction abnormalities or arrhythmias, such as participants with second degree (Type II) or third degree atrio-ventricular block.
3. History or evidence of current >=Class II congestive heart failure as defined by New York Heart Association (NYHA).
4. History of acute coronary syndromes (including unstable angina and myocardial infarction), coronary angioplasty, or stenting within the past 3 months. Participants with a history of stent placement requiring ongoing anti-coagulant therapy (e.g., clopidogrel, prasugrel) will not be permitted to enroll.
5. Known cardiac metastasis.
Participants with history of known bleeding disorder(s) or history of clinically significant hemorrhage (e.g., gastrointestinal, neurologic), within the past 6 months.
Therapeutic-dose anticoagulation (e.g., warfarin, low-molecular weight heparin [LMWH], or novel oral anticoagulants) must be discontinued and coagulation parameters must be normalized prior to the first dose of GSK525762 and abiraterone/enzalutimide. Prophylactic anticoagulation, with low doses (per standard practice) of agents such as LMWH, direct thrombin inhibitors, or factor Xa inhibitors is permitted.
Concurrent use of high dose aspirin (doses up to 81 milligrams (mg) oral dose daily allowed, or 100 mg, as per country standards) and non-steroidal anti-inflammatory drugs (NSAIDS), except for where NSAIDs provide documented benefit over other analgesics, and then to be used with caution including concomitant use of proton pump inhibitors).
Any acute toxicities due to prior chemotherapy and / or radiotherapy that have not resolved to a National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0 grade <=1 with the exception of chemotherapy induced alopecia and grade 2 peripheral neuropathy.
The participant has an active second malignancy other than curatively resected basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the bladder, or other cancers for which they are treated with curative intent with no active disease in the 3 years prior to enrollment.
Participants with known symptomatic brain metastasis are not suitable for enrolment. Participants with asymptomatic, stable, treated brain metastases are eligible for study entry.
History of seizure within 6 months of study treatment initiation or any condition that may predispose participant to seizure (e.g., prior cortical stroke or significant brain trauma) or who are currently being treated with cytochrome P450 enzyme inducing anti-epileptic drugs for seizures (use of anti-epileptic drugs to control pain is allowed in participants not suffering from seizures unless drug is excluded due to Cytochrome (CY)P3A4 induction - phenytoin, carbamazepine, phenobarbital).
History of loss of consciousness or transient ischemic attack within 12 months prior to enrollment.
Participants with symptomatic or impending cord compression unless appropriately treated beforehand and clinically stable and asymptomatic.
Current use of a prohibited medication or planned use of any forbidden medications during treatment with GSK525762 and abiraterone/enzalutamide. This includes medications that are potent inducers or inhibitors of CYP3A4 enzymes or strong inhibitors of CYP2C8.
Participants with gastrointestinal disorders likely to interfere with absorption of the study medication.
Participants with known bleeding diathesis.
Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment).
Initiating bisphosphonate or denosumab therapy or adjusting dose/regimen within 3 months prior to Week 1 Day 1. Participants on a stable bisphosphonate or denosumab therapy are eligible and may continue.
Any serious known immediate or delayed hypersensitivity reaction to GSK525762 or idiosyncrasy to drugs chemically related to the investigational drugs. Additionally, any known hypersensitivity to either enzalutamide, abiraterone or any excipients would be excluded.
Known history of human immunodeficiency virus (HIV).
Presence of hepatitis B surface antigen (HBsAg) or positive hepatitis C antibody test result at screening.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Los Angeles	California	90033	United States
GSK Investigational Site

ID	Title	Description
FG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
FG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 6, 2020	May 21, 2021

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)

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.

All Treated Population consisted of all participants who received at least one dose of GSK525762 or abiraterone or enzalutamide.

Posted

Count of Participants

Participants

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.
OG003	GSK525762 80 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG004	GSK525762 60 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG005	GSK525762 60 mg Alternate+Enzalutamide 160 mg	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.

Units	Counts
Participants	OG00010 OG0016 OG0024 OG003

Title

Denominators

Categories

Any AEs

Title	Measurements
	OG00010 OG0016 OG0024 OG003

Primary

Number of Participants With AEs Leading to Any Dose Reduction or Delays

All Treated Population.

Posted

Count of Participants

Participants

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.

Primary

Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment

Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs have been presented.

All Treated Population.

Posted

Count of Participants

Participants

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.

Primary

Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50)

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.

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.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002

Secondary

Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246

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.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter

Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.

Secondary

Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246

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.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Median

Full Range

Hours

Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg

Secondary

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

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.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*nanogram per milliliter

Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002

Secondary

Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246

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.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter

Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg

Secondary

Cmax of Abiraterone

Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter

Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.

Secondary

Tmax of Abiraterone

Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Median

Full Range

Hours

Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.

Secondary

AUC(0-tau) of Abiraterone

Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*nanogram per milliliter

Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.

Secondary

Ctrough of Abiraterone

Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter

Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.

Secondary

Cmax of Enzalutamide

Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis.

PK Population. Cmax could not be derived as only pre-dose samples were collected.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25

ID	Title	Description
OG000	GSK525762 80 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG001	GSK525762 60 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG002	GSK525762 60 mg Alternate+Enzalutamide 160 mg	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.

Secondary

Tmax of Enzalutamide

Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis.

PK Population. Tmax could not be derived as only pre-dose samples were collected.

Posted

Median

Full Range

Hours

Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25

ID	Title	Description
OG000	GSK525762 80 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG001	GSK525762 60 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG002	GSK525762 60 mg Alternate+Enzalutamide 160 mg	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.

Secondary

AUC(0-tau) of Enzalutamide

Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis.

PK Population. AUC(0-tau) could not be derived as only pre-dose samples were collected.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*microgram per milliliter

Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25

ID	Title	Description
OG000	GSK525762 80 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG001	GSK525762 60 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG002	GSK525762 60 mg Alternate+Enzalutamide 160 mg	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.

Secondary

Ctrough of Enzalutamide

Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis.

PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25

ID	Title	Description
OG000	GSK525762 80 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG001	GSK525762 60 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
OG002	GSK525762 60 mg Alternate+Enzalutamide 160 mg	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.

Secondary

Disease Control Rate at Week 24

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.

Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed.

Posted

Number

95% Confidence Interval

Percentage of participants

Week 24

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.

Secondary

Composite Response Rate

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.

Modified All Treated Population.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002

Secondary

Objective Response Rate

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.

Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed.

Posted

Number

Percentage of participants

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg

Secondary

Circulating Tumor Cells (CTC) Response Rate

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.

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.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.

Secondary

Prostate-specific Antigen (PSA) Response Rate at Week 4

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.

Modified All Treated Population.

Posted

Number

95% Confidence Interval

Percentage of participants

Week 4

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.

Secondary

Time to Disease Progression

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.

Modified All Treated Population.

Posted

Median

Inter-Quartile Range

Days

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002

Secondary

Radiographic Progression-free Survival (rPFS)

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.

Modified All Treated Population.

Posted

Median

Inter-Quartile Range

Days

Up to 21.3 montths

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg

Secondary

Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status

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.

All Treated Population. Only those participants with data available at the indicated time points were analyzed.

Posted

Count of Participants

Participants

Up to 21.3 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.

Secondary

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)

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.

Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Mean

Standard Deviation

Scores on a scale

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

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001

Secondary

Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours

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.

Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).

Posted

Mean

Standard Deviation

Scores on a scale

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

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.

Other Pre-specified

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study

All Treated Population

Posted

Count of Participants

Participants

Up to 3 years and 11 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.

Other Pre-specified

Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study

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.

All Treated Population

Posted

Count of Participants

Participants

Up to 3 years and 11 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg

Other Pre-specified

Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study

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.

All Treated Population

Posted

Count of Participants

Participants

Up to 3 years and 11 months

ID	Title	Description
OG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
OG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
OG002	GSK525762 40 mg+Abiraterone 1000 mg	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.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute kidney injury	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG0030 events0 affected10 at risk EG0040 events0 affected22 at risk EG0051 events1 affected21 at risk
Haematuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Clavicle fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Disseminated intravascular coagulation	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Femur fracture	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Intraventricular haemorrhage	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Myelitis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Myocarditis	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Paraplegia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Pneumonia	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0004 events4 affected10 at risk EG0014 events4 affected6 at risk EG0026 events4 affected4 at risk EG0036 events4 affected10 at risk EG00415 events9 affected22 at risk EG00515 events13 affected21 at risk
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0009 events7 affected10 at risk EG0013 events3 affected6 at risk EG0022 events1 affected4 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0008 events7 affected10 at risk EG0012 events2 affected6 at risk EG0020 events0 affected4 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0007 events5 affected10 at risk EG0012 events2 affected6 at risk EG0023 events2 affected4 at risk EG003
Asthenia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0014 events3 affected6 at risk EG0025 events4 affected4 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected10 at risk EG0012 events2 affected6 at risk EG0025 events2 affected4 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0006 events5 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0004 events4 affected10 at risk EG0012 events2 affected6 at risk EG0020 events0 affected4 at risk EG003
Platelet count decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0006 events4 affected10 at risk EG0015 events2 affected6 at risk EG0021 events1 affected4 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0021 events1 affected4 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0005 events4 affected10 at risk EG0014 events3 affected6 at risk EG0020 events0 affected4 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected6 at risk EG0022 events2 affected4 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0004 events3 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0021 events1 affected4 at risk EG003
Amylase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected10 at risk EG0010 events0 affected6 at risk EG0023 events2 affected4 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected6 at risk EG0021 events1 affected4 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 events3 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected6 at risk EG0021 events1 affected4 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected10 at risk EG0012 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
International normalised ratio increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected6 at risk EG0021 events1 affected4 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected10 at risk EG0010 events0 affected6 at risk EG0021 events1 affected4 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected10 at risk EG0010 events0 affected6 at risk EG0021 events1 affected4 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0004 events4 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Lipase increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Blood creatinine increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0002 events1 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected10 at risk EG0011 events1 affected6 at risk EG0020 events0 affected4 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Haematoma	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0022 events1 affected4 at risk EG003
Troponin I increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003
Weight decreased	Investigations	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected10 at risk EG0010 events0 affected6 at risk EG0020 events0 affected4 at risk EG003

ID	Term
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds

ID	Title	Description
BG000	GSK525762 60 mg+Abiraterone 1000 mg	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.
BG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.
BG002	GSK525762 40 mg+Abiraterone 1000 mg	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.
BG003	GSK525762 80 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
BG004	GSK525762 60 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.
BG005	GSK525762 60 mg Alternate+Enzalutamide 160 mg	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.
BG006	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	GSK525762 60 mg+Abiraterone 1000 mg	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.	9	10	4	10	10	10
EG001	GSK525762 60 mg Alternate+Abiraterone 1000 mg	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.	2	6	2	6	6	6
EG002	GSK525762 40 mg+Abiraterone 1000 mg	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.	2	4	0	4	4	4
EG003	GSK525762 80 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 80 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.	7	10	1	10	10	10
EG004	GSK525762 60 mg+Enzalutamide 160 mg	Participants received once daily oral dose of GSK525762 60 mg in combination with enzalutamide 160 mg up to maximum of 21.3 months.	8	22	6	22	22	22
EG005	GSK525762 60 mg Alternate+Enzalutamide 160 mg	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.	10	21	7	21	21	21

ID	Term
C554645	molibresib
C089740	abiraterone
C540278	enzalutamide
D011241	Prednisone