Solid Tumours
Conditions
Keywords
Abiraterone, Castrate-resistant prostate cancer, Androgen receptor targeted therapy, RP2D, Enzalutamide, GSK525762
Brief summary
This study aims to evaluate the combination of GSK525762 with other agents that have been shown to be effective in the treatment of CRPC or metastatic (m)CRPC. This study is designed to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) based on safety, tolerability, pharmacokinetic, and efficacy profiles of GSK525762 in combination with either abiraterone (Arm A) or enzalutamide (Arm B).
Interventions
DRUGGSK525762
GSK525762 will be administered.
DRUGAbiraterone
Abiraterone will be administered.
DRUGEnzalutamide
Enzalutamide will be administered.
DRUGPrednisone
Prednisone will be administered as a concomitant medication in combination with abiraterone
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This will be a two-arm, open-label dose escalation and dose expansion cohort study.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50) | Up to 21.3 months | 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. |
| Number of Participants With AEs Leading to Any Dose Reduction or Delays | Up to 21.3 months | 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. |
| Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment | Up to 21.3 months | Number of participants who withdrew due to toxicity and changes in safety assessment including laboratory parameters and vital signs have been presented. |
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 21.3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3 | 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. |
| Cmax of Abiraterone | Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3 | Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis. |
| Tmax of Abiraterone | Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3 | Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis. |
| AUC(0-tau) of Abiraterone | Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3 | Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis. |
| Ctrough of Abiraterone | Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3 | Blood samples were collected at indicated time points for PK analysis of abiraterone. PK parameters were calculated using standard non-compartmental analysis. |
| Cmax of Enzalutamide | Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25 | Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis. |
| Tmax of Enzalutamide | Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25 | Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis. |
| AUC(0-tau) of Enzalutamide | Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25 | Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis. |
| Objective Response Rate | Up to 21.3 months | 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. |
| Disease Control Rate at Week 24 | 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. |
| Composite Response Rate | Up to 21.3 months | 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. |
| Circulating Tumor Cells (CTC) Response Rate | Up to 21.3 months | 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. |
| Prostate-specific Antigen (PSA) Response Rate at Week 4 | 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. |
| Time to Disease Progression | Up to 21.3 months | 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. |
| Radiographic Progression-free Survival (rPFS) | Up to 21.3 montths | 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. |
| Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | Up to 21.3 months | 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. |
| 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) | 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 | 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. |
| Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | 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 | 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. |
| Ctrough of Enzalutamide | Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25 | Blood samples were collected at indicated time points for PK analysis of enzalutamide. PK parameters were calculated using standard non-compartmental analysis. |
| Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3 | 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 to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3 | 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. |
| 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 | Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3 | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Up to 3 years and 11 months | 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. |
| Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study | Up to 3 years and 11 months | 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. |
| Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Up to 3 years and 11 months | 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. |
Countries
Australia, Spain, United Kingdom, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 10 |
| 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. | 6 |
| 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. | 4 |
| 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. | 10 |
| 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. | 22 |
| 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. | 21 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 9 | 2 | 2 | 7 | 8 | 10 |
| Overall Study | Study terminated by Sponsor | 1 | 3 | 1 | 1 | 5 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 70.4 Years STANDARD_DEVIATION 7.69 | 68.0 Years STANDARD_DEVIATION 9.57 | 76.3 Years STANDARD_DEVIATION 4.11 | 69.3 Years STANDARD_DEVIATION 4.72 | 71.0 Years STANDARD_DEVIATION 6.49 | 69.1 Years STANDARD_DEVIATION 5.11 | 70.2 Years STANDARD_DEVIATION 6.32 |
| Race/Ethnicity, Customized Asian-East Asian Heritage | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White-Arabic/North African Heritage | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White-White/Caucasian/European Heritage | 7 Participants | 6 Participants | 4 Participants | 10 Participants | 21 Participants | 19 Participants | 67 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 10 Participants | 6 Participants | 4 Participants | 10 Participants | 22 Participants | 21 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 9 / 10 | 2 / 6 | 2 / 4 | 7 / 10 | 8 / 22 | 10 / 21 |
| other Total, other adverse events | 10 / 10 | 6 / 6 | 4 / 4 | 10 / 10 | 22 / 22 | 21 / 21 |
| serious Total, serious adverse events | 4 / 10 | 2 / 6 | 0 / 4 | 1 / 10 | 6 / 22 | 7 / 21 |
Outcome results
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.
Time frame: Up to 21.3 months
Population: All Treated Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment | 6 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment | 2 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment | 2 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment | 3 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment | 8 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment | 4 Participants |
Primary
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.
Time frame: Up to 21.3 months
Population: All Treated Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose reduction | 4 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose delay | 5 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose reduction | 1 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose delay | 2 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose reduction | 0 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose delay | 4 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose reduction | 7 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose delay | 8 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose reduction | 10 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose delay | 15 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose reduction | 7 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays | Dose delay | 12 Participants |
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.
Time frame: Up to 21.3 months
Population: All Treated Population consisted of all participants who received at least one dose of GSK525762 or abiraterone or enzalutamide.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 10 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 4 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 6 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 2 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 4 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 0 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 10 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 1 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 22 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 6 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AEs | 21 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAEs | 7 Participants |
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.
Time frame: Up to 21.3 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50) | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50) | 0 Percentage of participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50) | 0 Percentage of participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50) | 0 Percentage of participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50) | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Percentage of Participants With Greater Than or Equals to (>=)50 Percent (%) Decrease in Prostate-specific Antigen From Baseline (PSA50) | 0 Percentage of participants |
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.
Time frame: Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | 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 | GSK525762:Week3 Day1,n=4,1,3,5,6,6 | 2697.923 Hours*nanogram per milliliter | Geometric Coefficient of Variation 69.1 |
| GSK525762 60 mg+Abiraterone 1000 mg | 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 | GSK525762:Week1 Day1,n=8,2,2,6,9,8 | 4927.834 Hours*nanogram per milliliter | Geometric Coefficient of Variation 71.78 |
| GSK525762 60 mg+Abiraterone 1000 mg | 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 | GSK3529246:Week1 Day1,n=2,1,0,5,9,10 | 3765.196 Hours*nanogram per milliliter | Geometric Coefficient of Variation 0.47 |
| GSK525762 60 mg+Abiraterone 1000 mg | 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 | GSK3529246:Week3 Day1,n=2,2,2,4,12,7 | 4170.516 Hours*nanogram per milliliter | Geometric Coefficient of Variation 6.55 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | 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 | GSK3529246:Week1 Day1,n=2,1,0,5,9,10 | 4918.549 Hours*nanogram per milliliter | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | 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 | GSK3529246:Week3 Day1,n=2,2,2,4,12,7 | 5146.749 Hours*nanogram per milliliter | Geometric Coefficient of Variation 9.99 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | 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 | GSK525762:Week3 Day1,n=4,1,3,5,6,6 | 2580.877 Hours*nanogram per milliliter | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | 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 | GSK525762:Week1 Day1,n=8,2,2,6,9,8 | 4677.411 Hours*nanogram per milliliter | Geometric Coefficient of Variation 21.59 |
| GSK525762 40 mg+Abiraterone 1000 mg | 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 | GSK3529246:Week3 Day1,n=2,2,2,4,12,7 | 4598.235 Hours*nanogram per milliliter | Geometric Coefficient of Variation 16.28 |
| GSK525762 40 mg+Abiraterone 1000 mg | 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 | GSK525762:Week3 Day1,n=4,1,3,5,6,6 | 1561.908 Hours*nanogram per milliliter | Geometric Coefficient of Variation 13.67 |
| GSK525762 40 mg+Abiraterone 1000 mg | 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 | GSK525762:Week1 Day1,n=8,2,2,6,9,8 | 4172.282 Hours*nanogram per milliliter | Geometric Coefficient of Variation 31.08 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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 | GSK525762:Week1 Day1,n=8,2,2,6,9,8 | 1139.481 Hours*nanogram per milliliter | Geometric Coefficient of Variation 34.32 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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 | GSK3529246:Week1 Day1,n=2,1,0,5,9,10 | 4379.342 Hours*nanogram per milliliter | Geometric Coefficient of Variation 30.76 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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 | GSK525762:Week3 Day1,n=4,1,3,5,6,6 | 674.437 Hours*nanogram per milliliter | Geometric Coefficient of Variation 57.1 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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 | GSK3529246:Week3 Day1,n=2,2,2,4,12,7 | 3816.407 Hours*nanogram per milliliter | Geometric Coefficient of Variation 37.02 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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 | GSK3529246:Week3 Day1,n=2,2,2,4,12,7 | 3386.702 Hours*nanogram per milliliter | Geometric Coefficient of Variation 30.44 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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 | GSK525762:Week1 Day1,n=8,2,2,6,9,8 | 1261.529 Hours*nanogram per milliliter | Geometric Coefficient of Variation 102.14 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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 | GSK525762:Week3 Day1,n=4,1,3,5,6,6 | 660.607 Hours*nanogram per milliliter | Geometric Coefficient of Variation 14.41 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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 | GSK3529246:Week1 Day1,n=2,1,0,5,9,10 | 3373.990 Hours*nanogram per milliliter | Geometric Coefficient of Variation 19.73 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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 | GSK3529246:Week1 Day1,n=2,1,0,5,9,10 | 3306.018 Hours*nanogram per milliliter | Geometric Coefficient of Variation 31.84 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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 | GSK525762:Week3 Day1,n=4,1,3,5,6,6 | 386.950 Hours*nanogram per milliliter | Geometric Coefficient of Variation 37.03 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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 | GSK525762:Week1 Day1,n=8,2,2,6,9,8 | 959.452 Hours*nanogram per milliliter | Geometric Coefficient of Variation 60.97 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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 | GSK3529246:Week3 Day1,n=2,2,2,4,12,7 | 3082.516 Hours*nanogram per milliliter | Geometric Coefficient of Variation 33.36 |
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.
Time frame: Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | AUC(0-tau) of Abiraterone | Week 1 Day 1, n=5,1,1 | 432.368 Hours*nanogram per milliliter | Geometric Coefficient of Variation 56.74 |
| GSK525762 60 mg+Abiraterone 1000 mg | AUC(0-tau) of Abiraterone | Week 3 Day 1, n=1,2,1 | 1361.627 Hours*nanogram per milliliter | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | AUC(0-tau) of Abiraterone | Week 1 Day 1, n=5,1,1 | 148.871 Hours*nanogram per milliliter | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | AUC(0-tau) of Abiraterone | Week 3 Day 1, n=1,2,1 | 595.686 Hours*nanogram per milliliter | Geometric Coefficient of Variation 64.72 |
| GSK525762 40 mg+Abiraterone 1000 mg | AUC(0-tau) of Abiraterone | Week 1 Day 1, n=5,1,1 | 1405.809 Hours*nanogram per milliliter | — |
| GSK525762 40 mg+Abiraterone 1000 mg | AUC(0-tau) of Abiraterone | Week 3 Day 1, n=1,2,1 | 2185.039 Hours*nanogram per milliliter | — |
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.
Time frame: Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25
Population: PK Population. AUC(0-tau) could not be derived as only pre-dose samples were collected.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | AUC(0-tau) of Enzalutamide | NA Hours*microgram per milliliter |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | AUC(0-tau) of Enzalutamide | NA Hours*microgram per milliliter |
| GSK525762 40 mg+Abiraterone 1000 mg | AUC(0-tau) of Enzalutamide | NA Hours*microgram per milliliter |
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.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 13 Day 1,n=2,3,1,5,7,7 | 0.5 Scores on a scale | Standard Deviation 0.71 |
| GSK525762 60 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 17 Day 1,n=2,4,2,5,3,8 | 2.5 Scores on a scale | Standard Deviation 7.78 |
| GSK525762 60 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 3 Day 1,n=8,3,4,10,16,15 | 0.5 Scores on a scale | Standard Deviation 1.77 |
| GSK525762 60 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 2 Day 1,n=9,5,4,9,14,13 | 0.1 Scores on a scale | Standard Deviation 2.62 |
| GSK525762 60 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 4 Day 1,n=8,4,3,8,16,15 | 0.4 Scores on a scale | Standard Deviation 1.92 |
| GSK525762 60 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 5 Day 1,n=6,4,4,10,19,17 | -0.8 Scores on a scale | Standard Deviation 3.06 |
| GSK525762 60 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 9 Day 1,n=3,4,3,8,10,13 | 1.3 Scores on a scale | Standard Deviation 1.53 |
| GSK525762 60 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 21 Day 1,n=1,2,2,5,3,6 | 2.0 Scores on a scale | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 4 Day 1,n=8,4,3,8,16,15 | 0.5 Scores on a scale | Standard Deviation 1.91 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 13 Day 1,n=2,3,1,5,7,7 | 2.0 Scores on a scale | Standard Deviation 3 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 9 Day 1,n=3,4,3,8,10,13 | 1.3 Scores on a scale | Standard Deviation 0.96 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 5 Day 1,n=6,4,4,10,19,17 | -0.3 Scores on a scale | Standard Deviation 1.26 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 2 Day 1,n=9,5,4,9,14,13 | 0.8 Scores on a scale | Standard Deviation 2.86 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 17 Day 1,n=2,4,2,5,3,8 | 3.5 Scores on a scale | Standard Deviation 4.36 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 3 Day 1,n=8,3,4,10,16,15 | -1.7 Scores on a scale | Standard Deviation 1.53 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 21 Day 1,n=1,2,2,5,3,6 | 0.5 Scores on a scale | Standard Deviation 0.71 |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 61 Day 1,n=0,0,1,1,1,1 | -2.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 5 Day 1,n=6,4,4,10,19,17 | -1.0 Scores on a scale | Standard Deviation 0.82 |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 2 Day 1,n=9,5,4,9,14,13 | -2.3 Scores on a scale | Standard Deviation 1.71 |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 25 Day 1,n=0,0,1,2,3,4 | 3.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 13 Day 1,n=2,3,1,5,7,7 | 2.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 49 Day 1,n=0,0,1,3,1,3 | 2.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 17 Day 1,n=2,4,2,5,3,8 | -0.5 Scores on a scale | Standard Deviation 4.95 |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 21 Day 1,n=1,2,2,5,3,6 | -2.5 Scores on a scale | Standard Deviation 0.71 |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 45 Day 1,n=0,0,1,2,1,3 | 1.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 3 Day 1,n=8,3,4,10,16,15 | -1.8 Scores on a scale | Standard Deviation 1.89 |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 41 Day 1,n=0,0,1,3,1,1 | -1.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 37 Day 1,n=0,0,1,3,0,4 | 0.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 9 Day 1,n=3,4,3,8,10,13 | -0.3 Scores on a scale | Standard Deviation 2.52 |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 4 Day 1,n=8,4,3,8,16,15 | -1.3 Scores on a scale | Standard Deviation 1.15 |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 33 Day 1,n=0,0,1,3,2,2 | 1.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 29 Day 1,n=0,0,1,3,2,4 | -3.0 Scores on a scale | — |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 37 Day 1,n=0,0,1,3,0,4 | 1.7 Scores on a scale | Standard Deviation 2.08 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 2 Day 1,n=9,5,4,9,14,13 | 0.0 Scores on a scale | Standard Deviation 1.12 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 3 Day 1,n=8,3,4,10,16,15 | -1.0 Scores on a scale | Standard Deviation 2.05 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 4 Day 1,n=8,4,3,8,16,15 | -0.8 Scores on a scale | Standard Deviation 1.28 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 5 Day 1,n=6,4,4,10,19,17 | -0.9 Scores on a scale | Standard Deviation 2.13 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 9 Day 1,n=3,4,3,8,10,13 | -0.5 Scores on a scale | Standard Deviation 2.07 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 13 Day 1,n=2,3,1,5,7,7 | 0.2 Scores on a scale | Standard Deviation 1.92 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 17 Day 1,n=2,4,2,5,3,8 | -0.8 Scores on a scale | Standard Deviation 3.11 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 21 Day 1,n=1,2,2,5,3,6 | -0.2 Scores on a scale | Standard Deviation 2.49 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 25 Day 1,n=0,0,1,2,3,4 | 0.0 Scores on a scale | Standard Deviation 0 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 29 Day 1,n=0,0,1,3,2,4 | -0.7 Scores on a scale | Standard Deviation 1.15 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 33 Day 1,n=0,0,1,3,2,2 | 0.7 Scores on a scale | Standard Deviation 1.15 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 41 Day 1,n=0,0,1,3,1,1 | 1.3 Scores on a scale | Standard Deviation 1.53 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 45 Day 1,n=0,0,1,2,1,3 | 2.5 Scores on a scale | Standard Deviation 2.12 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 49 Day 1,n=0,0,1,3,1,3 | 0.3 Scores on a scale | Standard Deviation 1.53 |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 61 Day 1,n=0,0,1,1,1,1 | 0.0 Scores on a scale | — |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 73 Day 1,n=0,0,0,1,1,0 | 0.0 Scores on a scale | — |
| GSK525762 80 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 85 Day 1,n=0,0,0,1,1,0 | 3.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 73 Day 1,n=0,0,0,1,1,0 | -2.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 33 Day 1,n=0,0,1,3,2,2 | -1.5 Scores on a scale | Standard Deviation 2.12 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 45 Day 1,n=0,0,1,2,1,3 | -1.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 97 Day 1,n=0,0,0,0,1,0 | -3.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 2 Day 1,n=9,5,4,9,14,13 | 0.0 Scores on a scale | Standard Deviation 2.91 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 29 Day 1,n=0,0,1,3,2,4 | -3.5 Scores on a scale | Standard Deviation 0.71 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 13 Day 1,n=2,3,1,5,7,7 | -1.7 Scores on a scale | Standard Deviation 2.21 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 85 Day 1,n=0,0,0,1,1,0 | -3.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 17 Day 1,n=2,4,2,5,3,8 | -1.3 Scores on a scale | Standard Deviation 1.15 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 25 Day 1,n=0,0,1,2,3,4 | -1.3 Scores on a scale | Standard Deviation 5.69 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 3 Day 1,n=8,3,4,10,16,15 | 0.3 Scores on a scale | Standard Deviation 3.26 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 9 Day 1,n=3,4,3,8,10,13 | 0.2 Scores on a scale | Standard Deviation 2.49 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 61 Day 1,n=0,0,1,1,1,1 | -3.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 49 Day 1,n=0,0,1,3,1,3 | -3.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 21 Day 1,n=1,2,2,5,3,6 | -2.3 Scores on a scale | Standard Deviation 4.04 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 5 Day 1,n=6,4,4,10,19,17 | 0.7 Scores on a scale | Standard Deviation 3.38 |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 41 Day 1,n=0,0,1,3,1,1 | -3.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 4 Day 1,n=8,4,3,8,16,15 | 0.2 Scores on a scale | Standard Deviation 2.81 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 21 Day 1,n=1,2,2,5,3,6 | 1.0 Scores on a scale | Standard Deviation 1.79 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 49 Day 1,n=0,0,1,3,1,3 | 2.7 Scores on a scale | Standard Deviation 2.52 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 25 Day 1,n=0,0,1,2,3,4 | -1.0 Scores on a scale | Standard Deviation 1.15 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 4 Day 1,n=8,4,3,8,16,15 | 0.4 Scores on a scale | Standard Deviation 1.76 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 29 Day 1,n=0,0,1,3,2,4 | 0.8 Scores on a scale | Standard Deviation 4.19 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 33 Day 1,n=0,0,1,3,2,2 | -1.0 Scores on a scale | Standard Deviation 1.41 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 3 Day 1,n=8,3,4,10,16,15 | 0.0 Scores on a scale | Standard Deviation 1.51 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 37 Day 1,n=0,0,1,3,0,4 | 0.0 Scores on a scale | Standard Deviation 1.41 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 41 Day 1,n=0,0,1,3,1,1 | -1.0 Scores on a scale | — |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 2 Day 1,n=9,5,4,9,14,13 | 0.2 Scores on a scale | Standard Deviation 1.48 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 61 Day 1,n=0,0,1,1,1,1 | 3.0 Scores on a scale | — |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 45 Day 1,n=0,0,1,2,1,3 | 1.7 Scores on a scale | Standard Deviation 1.15 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 13 Day 1,n=2,3,1,5,7,7 | -0.4 Scores on a scale | Standard Deviation 2.15 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 17 Day 1,n=2,4,2,5,3,8 | -0.5 Scores on a scale | Standard Deviation 2.2 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 9 Day 1,n=3,4,3,8,10,13 | -0.4 Scores on a scale | Standard Deviation 2.4 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Change From Baseline in Brief Pain Inventory - Short Form (BPI-SF): Pain Intensity- Pain at Worst in Last 24 Hours | Week 5 Day 1,n=6,4,4,10,19,17 | -0.2 Scores on a scale | Standard Deviation 1.78 |
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.
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | 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) | Week 3 Day 1,n=6,0,1,4,3,7 | -8.3 Scores on a scale | Standard Deviation 23.57 |
| GSK525762 60 mg+Abiraterone 1000 mg | 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) | Week 4 Day 1,n=6,1,2,3,6,10 | -8.3 Scores on a scale | Standard Deviation 10.54 |
| GSK525762 60 mg+Abiraterone 1000 mg | 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) | Week 2 Day 1,n=6,1,2,4,4,8 | -8.3 Scores on a scale | Standard Deviation 12.91 |
| GSK525762 60 mg+Abiraterone 1000 mg | 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) | Week 17 Day 1,n=1,1,1,1,1,3 | -25.0 Scores on a scale | — |
| GSK525762 60 mg+Abiraterone 1000 mg | 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) | Week 13 Day 1,n=1,1,1,1,2,3 | -25.0 Scores on a scale | — |
| GSK525762 60 mg+Abiraterone 1000 mg | 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) | Week 9 Day 1,n=2,0,1,2,3,6 | -12.5 Scores on a scale | Standard Deviation 17.68 |
| GSK525762 60 mg+Abiraterone 1000 mg | 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) | Week 5 Day 1,n=3,0,1,3,5,9 | -8.3 Scores on a scale | Standard Deviation 14.43 |
| GSK525762 60 mg+Abiraterone 1000 mg | 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) | Week 1 Day 1,n=1,0,0,0,2,0 | 8.3 Scores on a scale | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | 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) | Week 4 Day 1,n=6,1,2,3,6,10 | 16.7 Scores on a scale | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | 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) | Week 2 Day 1,n=6,1,2,4,4,8 | 16.7 Scores on a scale | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | 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) | Week 13 Day 1,n=1,1,1,1,2,3 | 8.3 Scores on a scale | — |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | 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) | Week 17 Day 1,n=1,1,1,1,1,3 | -16.7 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 37 Day 1,n=0,0,1,0,0,3 | 0.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 33 Day 1,n=0,0,1,0,1,2 | 8.3 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 17 Day 1,n=1,1,1,1,1,3 | 16.7 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 45 Day 1,n=0,0,1,0,0,1 | -8.3 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 9 Day 1,n=2,0,1,2,3,6 | -8.3 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 41 Day 1,n=0,0,1,0,0,0 | 8.3 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 2 Day 1,n=6,1,2,4,4,8 | -12.5 Scores on a scale | Standard Deviation 29.46 |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 61 Day 1,n=0,0,1,0,0,1 | 16.7 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 13 Day 1,n=1,1,1,1,2,3 | 0.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 3 Day 1,n=6,0,1,4,3,7 | -16.7 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 49 Day 1,n=0,0,1,0,0,2 | 16.7 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 25 Day 1,n=0,0,1,0,0,1 | 0.0 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 21 Day 1,n=0,0,1,1,0,2 | 16.7 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 5 Day 1,n=3,0,1,3,5,9 | 8.3 Scores on a scale | — |
| GSK525762 40 mg+Abiraterone 1000 mg | 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) | Week 4 Day 1,n=6,1,2,3,6,10 | 0.0 Scores on a scale | Standard Deviation 11.79 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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) | Week 17 Day 1,n=1,1,1,1,1,3 | 0.0 Scores on a scale | — |
| GSK525762 80 mg+Enzalutamide 160 mg | 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) | Week 3 Day 1,n=6,0,1,4,3,7 | -4.2 Scores on a scale | Standard Deviation 8.33 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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) | Week 4 Day 1,n=6,1,2,3,6,10 | 5.6 Scores on a scale | Standard Deviation 9.62 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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) | Week 2 Day 1,n=6,1,2,4,4,8 | -2.1 Scores on a scale | Standard Deviation 4.17 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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) | Week 21 Day 1,n=0,0,1,1,0,2 | 0.0 Scores on a scale | — |
| GSK525762 80 mg+Enzalutamide 160 mg | 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) | Week 13 Day 1,n=1,1,1,1,2,3 | 0.0 Scores on a scale | — |
| GSK525762 80 mg+Enzalutamide 160 mg | 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) | Week 5 Day 1,n=3,0,1,3,5,9 | -5.6 Scores on a scale | Standard Deviation 9.62 |
| GSK525762 80 mg+Enzalutamide 160 mg | 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) | Week 9 Day 1,n=2,0,1,2,3,6 | -20.8 Scores on a scale | Standard Deviation 5.89 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 3 Day 1,n=6,0,1,4,3,7 | 2.8 Scores on a scale | Standard Deviation 4.81 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 4 Day 1,n=6,1,2,3,6,10 | 1.4 Scores on a scale | Standard Deviation 9.74 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 2 Day 1,n=6,1,2,4,4,8 | 0.0 Scores on a scale | Standard Deviation 13.61 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 5 Day 1,n=3,0,1,3,5,9 | 0.0 Scores on a scale | Standard Deviation 11.79 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 9 Day 1,n=2,0,1,2,3,6 | -30.6 Scores on a scale | Standard Deviation 12.73 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 13 Day 1,n=1,1,1,1,2,3 | -8.3 Scores on a scale | Standard Deviation 11.79 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 1 Day 1,n=1,0,0,0,2,0 | 4.2 Scores on a scale | Standard Deviation 5.89 |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 17 Day 1,n=1,1,1,1,1,3 | 0.0 Scores on a scale | — |
| GSK525762 60 mg+Enzalutamide 160 mg | 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) | Week 33 Day 1,n=0,0,1,0,1,2 | 0.0 Scores on a scale | — |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 17 Day 1,n=1,1,1,1,1,3 | -11.1 Scores on a scale | Standard Deviation 19.25 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 25 Day 1,n=0,0,1,0,0,1 | -8.3 Scores on a scale | — |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 29 Day 1,n=0,0,0,0,0,2 | -8.3 Scores on a scale | Standard Deviation 11.79 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 61 Day 1,n=0,0,1,0,0,1 | -16.7 Scores on a scale | — |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 3 Day 1,n=6,0,1,4,3,7 | -1.2 Scores on a scale | Standard Deviation 3.15 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 33 Day 1,n=0,0,1,0,1,2 | -8.3 Scores on a scale | Standard Deviation 11.79 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 13 Day 1,n=1,1,1,1,2,3 | 0.0 Scores on a scale | Standard Deviation 0 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 37 Day 1,n=0,0,1,0,0,3 | -2.8 Scores on a scale | Standard Deviation 4.81 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 9 Day 1,n=2,0,1,2,3,6 | -12.5 Scores on a scale | Standard Deviation 10.21 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 5 Day 1,n=3,0,1,3,5,9 | -0.0 Scores on a scale | Standard Deviation 11.02 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 45 Day 1,n=0,0,1,0,0,1 | 0.0 Scores on a scale | — |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 4 Day 1,n=6,1,2,3,6,10 | 2.5 Scores on a scale | Standard Deviation 16.22 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 49 Day 1,n=0,0,1,0,0,2 | -8.3 Scores on a scale | Standard Deviation 0 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 2 Day 1,n=6,1,2,4,4,8 | -1.0 Scores on a scale | Standard Deviation 12.94 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | 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) | Week 21 Day 1,n=0,0,1,1,0,2 | -4.2 Scores on a scale | Standard Deviation 5.89 |
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.
Time frame: Up to 21.3 months
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Circulating Tumor Cells (CTC) Response Rate | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Circulating Tumor Cells (CTC) Response Rate | 0 Percentage of participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Circulating Tumor Cells (CTC) Response Rate | 33 Percentage of participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Circulating Tumor Cells (CTC) Response Rate | 8 Percentage of participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Circulating Tumor Cells (CTC) Response Rate | 0 Percentage of participants |
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.
Time frame: Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Cmax of Abiraterone | Week 1 Day 1, n=10,5,4 | 77.962 Nanogram per milliliter | Geometric Coefficient of Variation 57.07 |
| GSK525762 60 mg+Abiraterone 1000 mg | Cmax of Abiraterone | Week 3 Day 1, n=4,4,2 | 149.673 Nanogram per milliliter | Geometric Coefficient of Variation 65.39 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Cmax of Abiraterone | Week 1 Day 1, n=10,5,4 | 63.369 Nanogram per milliliter | Geometric Coefficient of Variation 114.31 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Cmax of Abiraterone | Week 3 Day 1, n=4,4,2 | 87.554 Nanogram per milliliter | Geometric Coefficient of Variation 110.92 |
| GSK525762 40 mg+Abiraterone 1000 mg | Cmax of Abiraterone | Week 1 Day 1, n=10,5,4 | 122.496 Nanogram per milliliter | Geometric Coefficient of Variation 131.3 |
| GSK525762 40 mg+Abiraterone 1000 mg | Cmax of Abiraterone | Week 3 Day 1, n=4,4,2 | 146.924 Nanogram per milliliter | Geometric Coefficient of Variation 76.98 |
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.
Time frame: Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25
Population: PK Population. Cmax could not be derived as only pre-dose samples were collected.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Cmax of Enzalutamide | NA Microgram per milliliter |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Cmax of Enzalutamide | NA Microgram per milliliter |
| GSK525762 40 mg+Abiraterone 1000 mg | Cmax of Enzalutamide | NA Microgram per milliliter |
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.
Time frame: Up to 21.3 months
Population: Modified All Treated Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Composite Response Rate | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Composite Response Rate | 0 Percentage of participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Composite Response Rate | 0 Percentage of participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Composite Response Rate | 10 Percentage of participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Composite Response Rate | 5 Percentage of participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Composite Response Rate | 0 Percentage of participants |
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.
Time frame: Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Ctrough of Abiraterone | Week 1 Day 1, n=9,2,3 | 7.603 Nanogram per milliliter | Geometric Coefficient of Variation 93 |
| GSK525762 60 mg+Abiraterone 1000 mg | Ctrough of Abiraterone | Week 3 Day 1, n=2,4,1 | 15.114 Nanogram per milliliter | Geometric Coefficient of Variation 9.84 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Ctrough of Abiraterone | Week 1 Day 1, n=9,2,3 | 4.636 Nanogram per milliliter | Geometric Coefficient of Variation 1802.64 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Ctrough of Abiraterone | Week 3 Day 1, n=2,4,1 | 7.697 Nanogram per milliliter | Geometric Coefficient of Variation 69.99 |
| GSK525762 40 mg+Abiraterone 1000 mg | Ctrough of Abiraterone | Week 1 Day 1, n=9,2,3 | 11.263 Nanogram per milliliter | Geometric Coefficient of Variation 86.21 |
| GSK525762 40 mg+Abiraterone 1000 mg | Ctrough of Abiraterone | Week 3 Day 1, n=2,4,1 | 21.800 Nanogram per milliliter | — |
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.
Time frame: Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 25 Day 1, Pre-dose, n=2,2,2 | 10.103 Microgram per milliliter | Geometric Coefficient of Variation 8.13 |
| GSK525762 60 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 5 Day 1, Pre-dose, n=10,15,18 | 10.026 Microgram per milliliter | Geometric Coefficient of Variation 21.8 |
| GSK525762 60 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 17 Day 1, Pre-dose, n=4,2,4 | 8.621 Microgram per milliliter | Geometric Coefficient of Variation 22.86 |
| GSK525762 60 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 1 Day 1, Pre-dose, n=9,20,18 | 13.066 Microgram per milliliter | Geometric Coefficient of Variation 21.74 |
| GSK525762 60 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 9 Day 1, Pre-dose, n=6,6,13 | 10.021 Microgram per milliliter | Geometric Coefficient of Variation 27.01 |
| GSK525762 60 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 3 Day 1, Pre-dose, n=9,19,13 | 10.385 Microgram per milliliter | Geometric Coefficient of Variation 23.3 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 9 Day 1, Pre-dose, n=6,6,13 | 8.064 Microgram per milliliter | Geometric Coefficient of Variation 85.9 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 17 Day 1, Pre-dose, n=4,2,4 | 12.568 Microgram per milliliter | Geometric Coefficient of Variation 10.14 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 3 Day 1, Pre-dose, n=9,19,13 | 10.902 Microgram per milliliter | Geometric Coefficient of Variation 24.96 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 25 Day 1, Pre-dose, n=2,2,2 | 13.069 Microgram per milliliter | Geometric Coefficient of Variation 9.75 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 1 Day 1, Pre-dose, n=9,20,18 | 13.313 Microgram per milliliter | Geometric Coefficient of Variation 21.7 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 5 Day 1, Pre-dose, n=10,15,18 | 9.814 Microgram per milliliter | Geometric Coefficient of Variation 44.21 |
| GSK525762 40 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 5 Day 1, Pre-dose, n=10,15,18 | 12.561 Microgram per milliliter | Geometric Coefficient of Variation 31.27 |
| GSK525762 40 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 1 Day 1, Pre-dose, n=9,20,18 | 14.546 Microgram per milliliter | Geometric Coefficient of Variation 30.34 |
| GSK525762 40 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 3 Day 1, Pre-dose, n=9,19,13 | 11.497 Microgram per milliliter | Geometric Coefficient of Variation 27.34 |
| GSK525762 40 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 25 Day 1, Pre-dose, n=2,2,2 | 13.791 Microgram per milliliter | Geometric Coefficient of Variation 5.13 |
| GSK525762 40 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 9 Day 1, Pre-dose, n=6,6,13 | 12.056 Microgram per milliliter | Geometric Coefficient of Variation 30.12 |
| GSK525762 40 mg+Abiraterone 1000 mg | Ctrough of Enzalutamide | Week 17 Day 1, Pre-dose, n=4,2,4 | 10.267 Microgram per milliliter | Geometric Coefficient of Variation 58.45 |
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.
Time frame: Week 24
Population: Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Disease Control Rate at Week 24 | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Disease Control Rate at Week 24 | 40 Percentage of participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Disease Control Rate at Week 24 | 50 Percentage of participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Disease Control Rate at Week 24 | 40 Percentage of participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Disease Control Rate at Week 24 | 11 Percentage of participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Disease Control Rate at Week 24 | 29 Percentage of participants |
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.
Time frame: Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 950.319 Nanogram per milliliter | Geometric Coefficient of Variation 19.18 |
| GSK525762 60 mg+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 891.302 Nanogram per milliliter | Geometric Coefficient of Variation 36.79 |
| GSK525762 60 mg+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 280.892 Nanogram per milliliter | Geometric Coefficient of Variation 43.14 |
| GSK525762 60 mg+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 447.929 Nanogram per milliliter | Geometric Coefficient of Variation 39.3 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 318.772 Nanogram per milliliter | Geometric Coefficient of Variation 31.13 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 735.171 Nanogram per milliliter | Geometric Coefficient of Variation 21.63 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 993.154 Nanogram per milliliter | Geometric Coefficient of Variation 33.77 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 444.232 Nanogram per milliliter | Geometric Coefficient of Variation 26.74 |
| GSK525762 40 mg+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 364.151 Nanogram per milliliter | Geometric Coefficient of Variation 15.46 |
| GSK525762 40 mg+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 199.456 Nanogram per milliliter | Geometric Coefficient of Variation 32.94 |
| GSK525762 40 mg+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 559.711 Nanogram per milliliter | Geometric Coefficient of Variation 40.59 |
| GSK525762 40 mg+Abiraterone 1000 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 671.129 Nanogram per milliliter | Geometric Coefficient of Variation 30.44 |
| GSK525762 80 mg+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 427.580 Nanogram per milliliter | Geometric Coefficient of Variation 31.76 |
| GSK525762 80 mg+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 449.614 Nanogram per milliliter | Geometric Coefficient of Variation 49.54 |
| GSK525762 80 mg+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 284.298 Nanogram per milliliter | Geometric Coefficient of Variation 45.12 |
| GSK525762 80 mg+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 408.208 Nanogram per milliliter | Geometric Coefficient of Variation 39.86 |
| GSK525762 60 mg+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 321.750 Nanogram per milliliter | Geometric Coefficient of Variation 24.24 |
| GSK525762 60 mg+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 328.398 Nanogram per milliliter | Geometric Coefficient of Variation 39.74 |
| GSK525762 60 mg+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 158.409 Nanogram per milliliter | Geometric Coefficient of Variation 153.45 |
| GSK525762 60 mg+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 333.256 Nanogram per milliliter | Geometric Coefficient of Variation 48.86 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 171.527 Nanogram per milliliter | Geometric Coefficient of Variation 47.88 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 323.685 Nanogram per milliliter | Geometric Coefficient of Variation 25.77 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 356.615 Nanogram per milliliter | Geometric Coefficient of Variation 18.26 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Maximum Observed Plasma Concentration (Cmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 336.296 Nanogram per milliliter | Geometric Coefficient of Variation 43.28 |
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.
Time frame: Up to 21.3 months
Population: All Treated Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 0 | 2 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 1 | 7 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 2 | 1 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 3 | 0 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 4 | 0 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 5 | 0 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 1 | 4 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 3 | 0 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 5 | 0 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 0 | 0 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 2 | 2 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 4 | 0 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 5 | 0 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 4 | 0 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 3 | 1 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 2 | 0 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 0 | 0 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 1 | 3 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 3 | 0 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 1 | 5 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 2 | 3 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 5 | 0 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 4 | 0 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 0 | 2 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 0 | 1 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 4 | 0 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 1 | 16 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 2 | 3 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 3 | 1 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 5 | 0 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 3 | 1 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 2 | 6 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 4 | 0 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 5 | 0 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 1 | 13 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Worst-Case Post Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status | 0 | 1 Participants |
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.
Time frame: Up to 21.3 months
Population: Modified All Treated Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Objective Response Rate | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Objective Response Rate | 0 Percentage of participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Objective Response Rate | 0 Percentage of participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Objective Response Rate | 0 Percentage of participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Objective Response Rate | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Objective Response Rate | 0 Percentage of participants |
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.
Time frame: Week 4
Population: Modified All Treated Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Prostate-specific Antigen (PSA) Response Rate at Week 4 | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Prostate-specific Antigen (PSA) Response Rate at Week 4 | 17 Percentage of participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Prostate-specific Antigen (PSA) Response Rate at Week 4 | 0 Percentage of participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Prostate-specific Antigen (PSA) Response Rate at Week 4 | 0 Percentage of participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Prostate-specific Antigen (PSA) Response Rate at Week 4 | 0 Percentage of participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Prostate-specific Antigen (PSA) Response Rate at Week 4 | 0 Percentage of participants |
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.
Time frame: Up to 21.3 montths
Population: Modified All Treated Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Radiographic Progression-free Survival (rPFS) | 53.0 Days |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Radiographic Progression-free Survival (rPFS) | NA Days |
| GSK525762 40 mg+Abiraterone 1000 mg | Radiographic Progression-free Survival (rPFS) | NA Days |
| GSK525762 80 mg+Enzalutamide 160 mg | Radiographic Progression-free Survival (rPFS) | 416.0 Days |
| GSK525762 60 mg+Enzalutamide 160 mg | Radiographic Progression-free Survival (rPFS) | 141.0 Days |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Radiographic Progression-free Survival (rPFS) | 330.0 Days |
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.
Time frame: Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 3.000 Hours |
| GSK525762 60 mg+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 1.000 Hours |
| GSK525762 60 mg+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 0.800 Hours |
| GSK525762 60 mg+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 0.500 Hours |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 0.558 Hours |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 3.000 Hours |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 1.000 Hours |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 3.000 Hours |
| GSK525762 40 mg+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 3.000 Hours |
| GSK525762 40 mg+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 1.000 Hours |
| GSK525762 40 mg+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 0.950 Hours |
| GSK525762 40 mg+Abiraterone 1000 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 2.042 Hours |
| GSK525762 80 mg+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 1.042 Hours |
| GSK525762 80 mg+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 0.508 Hours |
| GSK525762 80 mg+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 2.067 Hours |
| GSK525762 80 mg+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 0.583 Hours |
| GSK525762 60 mg+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 0.933 Hours |
| GSK525762 60 mg+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 1.000 Hours |
| GSK525762 60 mg+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 2.917 Hours |
| GSK525762 60 mg+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 1.017 Hours |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=4,3,3,10,17,10 | 1.875 Hours |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=10,6,4,10,21,18 | 0.742 Hours |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=10,6,4,10,21,18 | 1.817 Hours |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Time to Cmax (Tmax) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=4,3,3,9,17,10 | 0.517 Hours |
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.
Time frame: Up to 21.3 months
Population: Modified All Treated Population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Time to Disease Progression | 88.0 Days |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Time to Disease Progression | NA Days |
| GSK525762 40 mg+Abiraterone 1000 mg | Time to Disease Progression | NA Days |
| GSK525762 80 mg+Enzalutamide 160 mg | Time to Disease Progression | 87.0 Days |
| GSK525762 60 mg+Enzalutamide 160 mg | Time to Disease Progression | 86.0 Days |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Time to Disease Progression | 84.0 Days |
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.
Time frame: Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Tmax of Abiraterone | Week 1 Day 1, n=10,5,4 | 1.133 Hours |
| GSK525762 60 mg+Abiraterone 1000 mg | Tmax of Abiraterone | Week 3 Day 1, n=4,4,2 | 1.000 Hours |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Tmax of Abiraterone | Week 1 Day 1, n=10,5,4 | 1.083 Hours |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Tmax of Abiraterone | Week 3 Day 1, n=4,4,2 | 2.000 Hours |
| GSK525762 40 mg+Abiraterone 1000 mg | Tmax of Abiraterone | Week 1 Day 1, n=10,5,4 | 0.750 Hours |
| GSK525762 40 mg+Abiraterone 1000 mg | Tmax of Abiraterone | Week 3 Day 1, n=4,4,2 | 3.017 Hours |
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.
Time frame: Pre-dose on Day 1 of Weeks 1, 3, 5, 9, 17 and 25
Population: PK Population. Tmax could not be derived as only pre-dose samples were collected.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Tmax of Enzalutamide | NA Hours |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Tmax of Enzalutamide | NA Hours |
| GSK525762 40 mg+Abiraterone 1000 mg | Tmax of Enzalutamide | NA Hours |
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.
Time frame: Pre-dose, 30 minutes, 1, 3, 6 to 12, 24 hours post-dose on Day 1 of Weeks 1 and 3
Population: PK Population. Only those participants with data available at the indicated time points were analyzed (indicated by n=X in category titles).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=8,3,3,9,20,17 | 58.995 Nanogram per milliliter | Geometric Coefficient of Variation 52.5 |
| GSK525762 60 mg+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=2,2,2,1,0,0 | 8.966 Nanogram per milliliter | Geometric Coefficient of Variation 93.46 |
| GSK525762 60 mg+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=3,3,2,7,13,8 | 48.223 Nanogram per milliliter | Geometric Coefficient of Variation 99.09 |
| GSK525762 60 mg+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=8,2,3,1,3,4 | 22.418 Nanogram per milliliter | Geometric Coefficient of Variation 192.37 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=8,3,3,9,20,17 | 68.379 Nanogram per milliliter | Geometric Coefficient of Variation 47.51 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=8,2,3,1,3,4 | 8.696 Nanogram per milliliter | Geometric Coefficient of Variation 72.93 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=2,2,2,1,0,0 | 4.555 Nanogram per milliliter | Geometric Coefficient of Variation 522.9 |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=3,3,2,7,13,8 | 48.291 Nanogram per milliliter | Geometric Coefficient of Variation 29.86 |
| GSK525762 40 mg+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=2,2,2,1,0,0 | 1.410 Nanogram per milliliter | Geometric Coefficient of Variation 48.34 |
| GSK525762 40 mg+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=3,3,2,7,13,8 | 63.526 Nanogram per milliliter | Geometric Coefficient of Variation 3.9 |
| GSK525762 40 mg+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=8,3,3,9,20,17 | 42.107 Nanogram per milliliter | Geometric Coefficient of Variation 52.26 |
| GSK525762 40 mg+Abiraterone 1000 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=8,2,3,1,3,4 | 13.664 Nanogram per milliliter | Geometric Coefficient of Variation 119.83 |
| GSK525762 80 mg+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week3 Day1,n=2,2,2,1,0,0 | 3.540 Nanogram per milliliter | — |
| GSK525762 80 mg+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=3,3,2,7,13,8 | 50.882 Nanogram per milliliter | Geometric Coefficient of Variation 77.1 |
| GSK525762 80 mg+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=8,3,3,9,20,17 | 46.011 Nanogram per milliliter | Geometric Coefficient of Variation 38.73 |
| GSK525762 80 mg+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=8,2,3,1,3,4 | 2.100 Nanogram per milliliter | — |
| GSK525762 60 mg+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=3,3,2,7,13,8 | 32.299 Nanogram per milliliter | Geometric Coefficient of Variation 60.18 |
| GSK525762 60 mg+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=8,2,3,1,3,4 | 5.053 Nanogram per milliliter | Geometric Coefficient of Variation 3035.92 |
| GSK525762 60 mg+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=8,3,3,9,20,17 | 37.765 Nanogram per milliliter | Geometric Coefficient of Variation 56.41 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week3 Day1,n=3,3,2,7,13,8 | 26.165 Nanogram per milliliter | Geometric Coefficient of Variation 76.95 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK525762:Week1 Day1,n=8,2,3,1,3,4 | 1.660 Nanogram per milliliter | Geometric Coefficient of Variation 34.6 |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Trough Concentration (Ctrough) of GSK525762 and Its Active Metabolites GSK3529246 | GSK3529246:Week1 Day1,n=8,3,3,9,20,17 | 38.200 Nanogram per milliliter | Geometric Coefficient of Variation 53.15 |
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.
Time frame: Up to 3 years and 11 months
Population: All Treated Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study | 6 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study | 2 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study | 2 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study | 3 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study | 8 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants Who Withdrew Due to Toxicity and Changes in Safety Assessment Until End of the Study | 4 Participants |
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.
Time frame: Up to 3 years and 11 months
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose reduction | 4 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose delay | 5 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose reduction | 1 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose delay | 2 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose reduction | 0 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose delay | 4 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose reduction | 7 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose delay | 8 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose reduction | 10 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose delay | 15 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose reduction | 7 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With AEs Leading to Any Dose Reduction or Delays Until End of the Study | Dose delay | 12 Participants |
Other Pre-specified
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.
Time frame: Up to 3 years and 11 months
Population: All Treated Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any AEs | 10 Participants |
| GSK525762 60 mg+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any SAEs | 4 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any AEs | 6 Participants |
| GSK525762 60 mg Alternate+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any SAEs | 2 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any AEs | 4 Participants |
| GSK525762 40 mg+Abiraterone 1000 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any SAEs | 0 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any AEs | 10 Participants |
| GSK525762 80 mg+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any SAEs | 1 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any AEs | 22 Participants |
| GSK525762 60 mg+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any SAEs | 6 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any AEs | 21 Participants |
| GSK525762 60 mg Alternate+Enzalutamide 160 mg | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Until End of the Study | Any SAEs | 7 Participants |