Dose-finding Study of GSK2636771 When Administered in Combination With Enzalutamide in Male Subjects With Metastatic Castration-Resistant Prostate Cancer

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02215096
• Collaborator: (none)
• Enrollment: 37
• Locations: 9
• Arms: 2
• Actual Duration (Months): 58.6
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This Phase I, open-label, dose-finding, multicenter study is designed to determine the recommended Phase II dose (RP2D) for the combination of an orally administered Phosphatidylinositol-4,5-bisphosphate 3-kinase beta (PI3K-beta) inhibitor (GSK2636771) with enzalutamide. Subjects with phosphatase and tensin homolog (PTEN)-deficient metastatic castration-resistant prostate cancer (mCRPC) who are receiving a stable dose of enzalutamide with a recently demonstrated progression (either by RECIST [Response Evaluation Criteria In Solid Tumors] version 1.1, prostate-specific antigen [PSA] progression, and/or progression in bone) per the Prostate Cancer Working Group 2 (PCWG2) criteria will be enrolled. Eligible subjects will be enrolled in the Dose-Escalation Phase to determine the maximum tolerated dose (MTD) of the combination therapy using a modified 3+3 dose escalation procedure. The safety, pharmacokinetics (PK) and clinical efficacy will also be assessed to guide the selection of the RP2D. The starting dose will be GSK2636771 300 mg once daily in combination with the recommended dose (160 milligram [mg] once daily) of oral enzalutamide. Once the RP2D has been established, additional subjects will be enrolled in the Dose Expansion Phase to further evaluate the safety, PK and preliminary clinical activity. Safety assessments will be performed throughout the study including physical examinations, vital signs, clinical laboratory tests, 12 lead electrocardiograms and monitoring of adverse events. Blood samples will be collected for pharmacokinetic analysis. Subjects will continue treatment until an unacceptable toxicity, disease progression, withdrawal of consent or death occurs. A post-treatment follow-up visit will be performed within 30 days of the last dose of study treatment. Xtandi is a registered trademark of Astellas Pharma Inc

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: GSK2636771; Drug: Enzalutamide	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Open-label, Dose-finding Study of GSK2636771 Administered in Combination With Enzalutamide (Xtandi^TM ) in Male Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
• Actual Study Start Date: Nov 13, 2014
• Actual Primary Completion Date: Oct 3, 2019
• Actual Study Completion Date: Oct 3, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1-Dose Escalation Subject receiving a stable dose of enzalutamide 160 mg once daily will receive GSK2636771 following a modified 3+3 dose escalation procedure (Cohort -1: 200 mg, Cohort 1: 300 mg and Cohort 2: 400 mg) to evaluate the safety and PK for each combination dose level and to guide selection of the RP2D of the combination. If the combination doses in Cohort 1 are not tolerable, lower doses as defined in the de-escalation cohort (Cohort -1) will be evaluated. If the de-escalation cohort (Cohort -1) is not tolerable, further dose-escalation using a continuous daily dosing schedule for both compounds simultaneously will be terminated. Additional dose levels of GSK2636771 or alternative dosing schedules may be explored based upon ongoing assessment of safety and PK. Dose modification decisions will be made utilizing all available data at the end of each DLT determination period (28 days).	Drug: GSK2636771; GSK is available as 100 mg hard gelatin oral capsule to be taken once daily/continuous until treatment withdrawal under fasting conditions for at least 1hour (h) before and 2h after dosing with approximately 200 mL of water; Drug: Enzalutamide; Enzalutamide will be sourced locally from commercial stock for sites in countries where it is approved
Experimental: Phase 2- Dose Expansion Additional 20 subjects will be assigned to receive GSK2636771 at the MTD or RP2D determined in the Dose-Escalation Phase while continuing treatment with enzalutamide to evaluate the long-term safety of the combination as well as the 12-week non-PD rate	Drug: GSK2636771; GSK is available as 100 mg hard gelatin oral capsule to be taken once daily/continuous until treatment withdrawal under fasting conditions for at least 1hour (h) before and 2h after dosing with approximately 200 mL of water; Drug: Enzalutamide; Enzalutamide will be sourced locally from commercial stock for sites in countries where it is approved

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period [Up to Week 2]

   An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is 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, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as alanine aminotransferase (ALT) >=3 times upper limit of normal (ULN), and bilirubin >=2 times ULN (>35 percent [%] direct) (or ALT >=3 times ULN and international normalized ratio (INR) >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.

2. Number of Participants With Non-SAEs and SAEs During Combination Treatment Period [Up to maximum 675 days]

   An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is 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, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as ALT >=3 times ULN, and bilirubin >=2 times ULN (>35% direct) (or ALT >=3 times ULN and INR >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.

3. Number of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period [Up to Day 28]

   An event was considered as DLT if the event was attributed (definitely, probably or possibly) to study treatment, occured within the first 28 days of combination treatment (DLT reporting period), and met one of the following criteria: Febrile neutropenia of any grade or duration as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 4 neutropenia lasting >5 days, Grade 3 or greater non-hematologic toxicity that cannot be controlled with routine supportive measures, Grade 4 thrombocytopenia, ALT >3 times ULN with bilirubin >2 times ULN or ALT >=3 times ULN and >=1.5 times Baseline ALT value, if enrolled with liver metastases/tumor infiltration at Baseline), together with bilirubin >=2 times ULN.

4. Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, MCH, MCV, Monocytes, Total Neutrophils, Platelet Count, WBC Count [Baseline (Day 1), Weeks 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88]

   Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, total neutrophils, platelet count and white blood cells (WBCs) count. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

5. Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: International Normalized Ratio (INR), Prothrombin Time (PT), Partial Thromboplastin Time (PTT) [Baseline (Day 1), Week 4]

   Blood samples were collected to analyze the hematology parameters: INR, PT and PTT. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

6. Percent Change From Baseline in Chemistry Parameters in Combination Treatment Period:ALT, Albumin, ALP, AST, Calcium, CO2, Chloride, Creatinine, Direct Bilirubin, Glucose, Lactate Dehydrogenase, Magnesium, Potassium, Sodium, Total Bilirubin, Total Protein [Baseline (Day 1), Weeks 1,2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88]

   Blood samples were collected to analyze the chemistry parameters: ALT, Albumin, Alkaline phosphatase (ALP), Aspartate amino transferase (AST), Calcium, Carbon dioxide (CO2), Chloride, Creatinine, Direct bilirubin, Glucose, Lactate dehydrogenase, Magnesium, Potassium, Sodium, Total bilirubin and Total protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

7. Percent Change From Baseline in Chemistry Parameters During Combination Treatment Period: Blood Urea Nitrogen (BUN), Uric Acid [Baseline (Day 1), Weeks 1, 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88]

   Blood samples were collected to analyze the chemistry parameters: BUN and uric acid. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

8. Percent Change From Baseline in Urine Concentration of Calcium, Creatinine Concentration, Magnesium, Phosphate, Protein During Combination Treatment Period [Baseline (Day 1), Weeks 1, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48, 56 and 64]

   Urine samples were collected to analyze the urinalysis parameters: Calcium, Creatinine concentration (conc), Magnesium, Phosphate and Protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

9. Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings During Combination Treatment Period [Weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80 and 88]

   A 12-lead ECG was obtained after the participant had rested at least 5 minutes in a semi-recumbent or supine position at each time point during the study using ECG machine that automatically measured PR, QRS, QT and Corrected QT interval (QT duration corrected for heart rate by Bazett's formula [QTcB] and Fridericia's formula [QTcF]). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal clinical significant ECG findings are presented.

10. Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Results by Maximum Grade Increase Post-Baseline Relative to Baseline During Combination Treatment Period [Up to maximum 654 days]

    SBP and DBP were measured after resting for 5 minutes in semi-supine position. SBP and DBP were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. 'Any grade increase' is defined as an increase in CTCAE grade relative to Baseline grade. For SBP, Grade 0: <120 millimeters of mercury [mmHg]), Grade 1: 120-139 mmHg, Grade 2: 140-159 mmHg, Grade 3:>=160 mmHg. For DBP, Grade 0: <80 mmHg, Grade 1: 80-89 mmHg, Grade 2: 90-99 mmHg, Grade 3: >=100 mmHg. Higher grade indicate worst outcome. Data for worst-case post-Baseline is reported.

11. Number of Participants With Worst Case Post-Baseline Results for Heart Rate During Combination Treatment Period [Up to maximum 654 days]

    Heart rate was measured after resting for 5 minutes in semi-supine position. The clinical concern range for heart rate was: low: decrease to <60 beats per minute (bpm) and high: increase to >100 bpm. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decrease to <60 bpm' and 'increase to >100 bpm' during post-Baseline visits. Data for worst case post-Baseline is reported.

12. Number of Participants With Worst Case Post-Baseline Results for Body Temperature During Combination Treatment Period [Up to maximum 654 days]

    Temperature was measured after resting for 5 minutes in semi-supine position. The clinical concern range for body temperature was: low: decrease to <=35 degrees celsius, high: increase to >=38 degrees celsius. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decreased to <=35 degree celsius' and 'increased to >=38 degrees celsius' during post-Baseline visits. Data for worst-case post-Baseline is presented.

13. Non-progressive Disease (Non-PD) Rate at Week 12 According to Prostate Cancer Working Group 2 (PCWG2) Criteria in GSK2636771 200mg/Enzalutamide 160mg - Overall Arm [At Week 12]

    The 12-week non-PD rate was defined as percentage of participants without progression(non-PD) at Week12 as determined from Prostate-specific antigen(PSA) results, radiographic assessment per Response Evaluation Criteria In Solid Tumors(RECIST)1.1 and bone scan.Disease progression was defined by 1 or more of the following:PSA progression alone; PSA progression according to the PCWG2 criteria with accompanying progression by RECIST1.1 or bone scan for participants with soft tissue Baseline disease; Bone progression on bone scan according to PCWG2 criteria; or Radiographic progression in soft tissue or bone by RECIST1.1 for participants with Baseline disease.Modified All Treated Clinical Activity Population consisted of all participants who received at least 1 dose of GSK2636771 and who were treated at the same dose as dose expansion cohort and have been on study drug for at least 12weeks or have discontinued study treatment due to disease progression, died or withdrawn for any reason.

Secondary Outcome Measures

1. Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate at 12 Weeks During Combination Treatment Period [At Week 12]

   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 until last post-treatment follow-up visit or initiation of new anti-cancer therapy and confirmed after 3 or more weeks by an additional PSA evaluation. Confirmed PSA50 is defined as decline of >=50% in PSA concentration from Baseline.

2. Objective Response Rate (ORR) During Combination Treatment Period [Up to maximum 654 days]

   ORR is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per RECIST Version (v) 1.1 criteria; where CR: Disappearance of all target lesions; PR: at least 30% decrease in the sum of the longest diameter of target lesions with reference to Baseline sum of diameters.

3. Time to PSA Progression According to PCWG2 Criteria During Combination Treatment Period [Up to maximum 654 days]

   Time to PSA progression is defined as the time from combination study treatment start until the first PSA progression per PCWG2 criteria (confirmed if there has been a PSA decline from Baseline). Time to PSA was analyzed using Kaplan-Meier methods. Median and inter-quartile range (first and third quartile) are presented.

4. Time to Radiological Progression According to PCWG2 Criteria During Combination Treatment Period [Up to maximum 654 days]

   Time to radiological progression is defined as the time from combination study treatment start until the first radiological progression by PCWG2 criteria. Time to radiological progession was analyzed using Kaplan-Meier methods. For participants who do not progress, participants were censored at the time of last radiological scan or date of death. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of GSK2636771 drug. Median and inter-quartile range (first and third quartile) are presented.

5. Radiological Progression Free Survival (rPFS) Per PCWG2 Criteria During Combination Treatment Period [Up to maximum 654 days]

   rPFS is defined as the interval of time (in weeks) between the date of first dose of GSK2636771 and the earlier of the date of disease progression as assessed by the investigator per RECIST version 1.1 criteria and the date of death due to any cause. For participants who do not progress or die, participants were censored at the time of last radiological scan. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of GSK2636771 drug. rPFS was analyzed using Kaplan-Meier methods. Median and inter-quartile range (first and third quartile) are presented.

6. Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period [Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose]

   Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2636771.

7. Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period [Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose]

   Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2636771. Pharmacokinetic Concentration Population consisted of all participants in the All Treated Safety Population for whom a blood sample for pharmacokinetics were obtained, analyzed, and was measurable.

8. Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period [Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose]

   Blood samples were collected at indicated time points for pharmacokinetic analysis of enzalutamide.

9. Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period [Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose]

   Blood samples were collected at indicated time points for pharmacokinetic analysis of enzalutamide.

10. Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period [Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose]

    Blood samples were collected at indicated time points for pharmacokinetic analysis of N-desmethyl enzalutamide.

11. Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period [Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose]

    Blood samples were collected at indicated time points for pharmacokinetic analysis of N-desmethyl enzalutamide.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Signed written informed consent provided

• Males >=18 years of age (at the time consent is obtained)

• Histologically or cytologically confirmed diagnosis of prostate adenocarcinoma, surgically castrated or continuous medical castration (for >=8 weeks prior to Screening)

• Serum testosterone <50 nanogram per deciliter (ng/dL) (1.7 nanomole per liter [nM/L])

• PTEN deficient tumor as documented from archival or fresh (from biopsy) tumor tissue analyzed by GlaxoSmithKline selected laboratory

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Completed at least 12 weeks of prior continuous therapy with enzalutamide. A 2 week or less treatment (enzalutamide) holiday will be permitted prior to initiating study treatment.

• Most recent enzalutamide dose received is 160 mg once daily with no change in dose for at least 2 weeks prior to Screening.

• Has progressive disease at time of enrollment defined as one or more of the following criteria: PSA progression defined by PCWG2 criteria or soft tissue disease progression defined by RECIST 1.1 or bone disease progression defined by PCWG2 criteria Able to swallow and retain orally administered medication.

• Adequate baseline organ function.

• Must have a QT interval corrected for heart rate according to Fridericia's formula (QTcF) <470 milli seconds (msec) or <480 msec with bundle branch block.

• Male subject with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from time of Screening until 3 months after the last dose of study treatment.

Exclusion Criteria:

• Prior treatment with: anti-cancer therapy (e.g., chemotherapy with delayed toxicity, immunotherapy, biologic therapy or chemoradiation) within 21 days (or within 42 days if prior nitrosourea or mitomycin C containing therapy) prior to enrollment and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to enrolment. Subjects may remain on luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide, goserelin, triptorelin or histrelin). Subjects must have prior enzalutamide treatment; Any PI3K, AKT or mammalian target of rapamycin (mTOR) inhibitors; Investigational drug(s) within 30 days or 5 half-lives, whichever is longer, prior to enrollment

• Prior malignancy other than CRPC. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible.

• Current use of or anticipated requirement during the study of prohibited medication(s) (any investigational drug(s), Other anti-cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormone therapy other than for replacement), AR antagonists (e.g., bicalutamide, flutamide, nilutamide), 5-alpha reductase inhibitors (e.g., finasteride, dutasteride), Androgens (e.g., testosterone, dihydroepiandrosterone), Herbal medication(s) that may affect PSA levels (e.g., saw palmetto), Other herbal medications including, but not limited to: St. John's wort, kava, ephedra (ma huang), gingko biloba, yohimbe and ginseng)

• Any unresolved >=Grade 2 (per CTCAE v 4.0) toxicity from previous anti-cancer therapy at the time of enrollment, except alopecia or Grade 2 anemia (if hemoglobin is >9.0 g/dL)

• Any >=Grade 2 hypophosphatemia (per CTCAE v4.0) at the time of enrolment

• Serum calcium >=Grade 1 (per CTCAE v4.0) at time of enrolment, unless ionized calcium is within normal range

• Presence of any clinically significant gastrointestinal (GI) abnormality or other condition(s) that may alter absorption such as malabsorption syndrome or major resection of the stomach or substantial portion of the small intestine

• Active peptic ulcer disease or history of abdominal fistula, GI perforation, or intra abdominal abscess within 28 days prior to enrolment

• Previous major surgery within 28 days prior to enrolment

• Known active infection requiring intravenous (IV) or oral anti-infective treatment

• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.

• A positive pre-study drug/alcohol screening (testing at time of screening is not required).

• A positive test for human immunodeficiency virus (HIV) antibody (testing at time of screening is not required).

• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal or cardiac disease)

• History of seizure or any condition that may predispose subject to seizure (e.g., prior cortical stroke or significant brain trauma). History of loss of consciousness or transient ischemic attack within 12 months of randomization

• History or evidence of cardiovascular risk including any of the following: Clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block; history of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, stenting, or bypass grafting within the past 6 months prior to enrolment, Class III or IV heart failure as defined by the New York Heart Association functional classification system, LVEF below 50%; known cardiac metastases

• Poorly controlled hypertension (defined as systolic blood pressure of>=150 millimeter of mercury (mmHg) or diastolic blood pressure of >100 mmHg based on a mean of three measurements at approximately 2-minute intervals)

• History of congenital platelet function defect (e.g., Bernard-Soulier syndrome, Chediak-Higashi syndrome, Glanzmann thrombasthenia, storage pool defect)

• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2636771or enzalutamide or excipients.

• Any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.

• Exposure to more than 4 investigational medicinal products within 12 months prior to the first dose of study treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Duarte	California	United States	91010
2	GSK Investigational Site	Los Angeles	California	United States	90033
3	GSK Investigational Site	Los Angeles	California	United States	90095
4	GSK Investigational Site	Washington	District of Columbia	United States	20007
5	GSK Investigational Site	Detroit	Michigan	United States	48201
6	GSK Investigational Site	New York	New York	United States	10016
7	GSK Investigational Site	Houston	Texas	United States	77030
8	GSK Investigational Site	London		United Kingdom	SE1 9RT
9	GSK Investigational Site	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jan 27, 2017
• Statistical Analysis Plan - Mar 3, 2020

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02215096
• Other Study ID Numbers: 200331; 2013-005111-27
• First Posted: Aug 13, 2014
• Last Update Posted: Oct 22, 2020
• Last Verified: Sep 1, 2020

• Keywords provided by GlaxoSmithKline: enzalutamide; metastatic castration-resistant prostate cancer; GSK2636771; PI3K-beta; PTEN deficiency
• Additional relevant MeSH terms: Prostatic Neoplasms; GSK2636771

Study Results

Participant Flow

Recruitment Details	This was an open-label, dose finding study of GSK2636771 administered in combination with Enzalutamide in male participants with Metastatic Castration-Resistant Prostate Cancer (mC-RPC) conducted at 7 centers across United Kingdom and United States.
Pre-assignment Detail	A total 37 participants were enrolled in this study and entered in the enzalutamide run-in period, of which 36 participants received GSK2636771+enzalutamide and completed the combination treatment period (TP).

Arm/Group Title	Enzalutamide Only (run-in Period)	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received enzalutamide monotherapy at the approved dose of 160 milligrams (mg) once daily orally for 14 days in run-in period to achieve near-steady-state levels of enzalutamide prior to initiating combination therapy with GSK2636771. Participants who completed the enzalutamide run-in period continued with the combination therapy with GSK2636771.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Period Title: Run-In Period (Up to Week 2)
STARTED	37	0	0	0	0
COMPLETED	36	0	0	0	0
NOT COMPLETED	1	0	0	0	0
Period Title: Run-In Period (Up to Week 2)
STARTED	0	11	11	12	2
COMPLETED	0	9	10	10	1
NOT COMPLETED	0	2	1	2	1

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Participant received enzalutamide monotherapy at the approved dose of 160 mg once daily orally for 14 days in run-in period to achieve near-steady-state levels of enzalutamide prior to initiating combination therapy with GSK2636771. In combination treatment period, participants received GSK2636771 200 mg or 300 mg or 400 mg once daily orally in combination with enzalutamide 160 mg once daily orally in dose escalation/ expansion cohorts.
Overall Participants	37
Age, Customized (Count of Participants)
<18 years	0 0%
18-64 years	9 24.3%
65-74 years	20 54.1%
>=75 years	8 21.6%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	37 100%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	1 2.7%
Asian-South East Asian Heritage	1 2.7%
White-White/Caucasian/European Heritage	34 91.9%
Native Hawaiian or Other Pacific Islander	1 2.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period
Description	An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is 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, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as alanine aminotransferase (ALT) >=3 times upper limit of normal (ULN), and bilirubin >=2 times ULN (>35 percent [%] direct) (or ALT >=3 times ULN and international normalized ratio (INR) >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.
Time Frame	Up to Week 2

Outcome Measure Data

Analysis Population Description

All Treated Safety Population consisted of all participants who received at least one dose of Enzalutamide.

Arm/Group Title	Enzalutamide Only (run-in Period)
Arm/Group Description	Participants received enzalutamide monotherapy at the approved dose of 160 mg once daily orally for 14 days in run-in period to achieve near-steady-state levels of enzalutamide prior to initiating combination therapy with GSK2636771. Participants who completed the enzalutamide run-in period continued with the combination therapy with GSK2636771.
Measure Participants	37
Non-SAEs	11 29.7%
SAEs	1 2.7%

2. Primary Outcome

Title	Number of Participants With Non-SAEs and SAEs During Combination Treatment Period
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is 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, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as ALT >=3 times ULN, and bilirubin >=2 times ULN (>35% direct) (or ALT >=3 times ULN and INR >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.
Time Frame	Up to maximum 675 days

Outcome Measure Data

Analysis Population Description

All Treated Safety Population consisted of all participants who received at least one dose of GSK2636771 or Enzalutamide. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	2
Non-SAEs	11 29.7%	11 NaN	12 NaN	2 NaN
SAEs	2 5.4%	2 NaN	2 NaN	0 NaN

3. Primary Outcome

Title	Number of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period
Description	An event was considered as DLT if the event was attributed (definitely, probably or possibly) to study treatment, occured within the first 28 days of combination treatment (DLT reporting period), and met one of the following criteria: Febrile neutropenia of any grade or duration as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 4 neutropenia lasting >5 days, Grade 3 or greater non-hematologic toxicity that cannot be controlled with routine supportive measures, Grade 4 thrombocytopenia, ALT >3 times ULN with bilirubin >2 times ULN or ALT >=3 times ULN and >=1.5 times Baseline ALT value, if enrolled with liver metastases/tumor infiltration at Baseline), together with bilirubin >=2 times ULN.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	2
Count of Participants [Participants]	1 2.7%	0 NaN	2 NaN	2 NaN

4. Primary Outcome

Title	Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, MCH, MCV, Monocytes, Total Neutrophils, Platelet Count, WBC Count
Description	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, total neutrophils, platelet count and white blood cells (WBCs) count. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Time Frame	Baseline (Day 1), Weeks 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	2
Basophils, Week 2, n=5,4,5,1	20.000 (103.6822)	0.000 (0.0000)	30.000 (48.0885)	33.330 (NA)
Basophils, Week 3, n=5,5,6,1	0.000 (70.7107)	27.500 (43.6606)	-16.270 (38.4859)	0.000 (NA)
Basophils, Week 4, n=5,4,5,1	-16.666 (79.9314)	25.000 (50.0000)	26.666 (43.4612)	33.330 (NA)
Basophils, Week 5, n=4,4,5,0	-37.500 (94.6485)	25.000 (50.0000)	27.380 (46.9143)
Basophils, Week 8, n=4,4,4,0	-12.500 (25.0000)	25.000 (50.0000)	139.583 (188.2399)
Basophils, Week 12, n=3,4,3,0	0.000 (100.0000)	25.000 (50.0000)	51.190 (42.3084)
Basophils, Week 16, n=3,4,1,0	-33.333 (57.7350)	16.668 (33.3350)	0.000 (NA)
Basophils, Week 20, n=2,3,1,0	-50.000 (70.7107)	0.000 (0.0000)	50.000 (NA)
Basophils, Week 24, n=2,1,0,0	-50.000 (70.7107)	0.000 (NA)
Basophils, Week 28, n=1,0,0,0	100.000 (NA)
Basophils, Week 32, n=2,1,0,0	0.000 (141.4214)	0.000 (NA)
Basophils, Week 36, n=2,1,0,0	-50.000 (70.7107)	0.000 (NA)
Basophils, Week 40, n=0,1,0,0	100.000 (NA)
Basophils, Week 44, n=0,1,0,0	0.000 (NA)
Eosinophils, Week 2, n=9,8,8,2	-26.321 (47.4470)	-8.754 (30.6984)	-19.135 (47.3780)	-2.175 (3.0759)
Eosinophils, Week 3, n=8,8,9,2	13.085 (40.8232)	13.994 (65.2691)	4.704 (68.1450)	54.350 (64.5588)
Eosinophils, Week 4, n=8,8,8,2	11.136 (36.6046)	-3.626 (75.4907)	13.333 (57.7624)	-2.175 (3.0759)
Eosinophils, Week 5, n= 7,7,8,1	54.970 (110.7083)	-23.809 (43.1487)	9.708 (42.6803)	100.000 (NA)
Eosinophils, Week 8, n=6,7,8,1	16.857 (53.6217)	5.953 (32.8832)	90.104 (102.6830)	-100.000 (NA)
Eosinophils, Week 12, n=4,6,6,1	31.250 (47.3242)	1.390 (41.6394)	72.578 (129.4696)	0.000 (NA)
Eosinophils, Week 16, n=5,5,3,1	2.120 (15.8040)	-17.626 (34.2120)	62.500 (119.2424)	0.000 (NA)
Eosinophils, Week 20, n=3,5,3,1	9.090 (15.7443)	15.000 (81.7340)	66.667 (115.4701)	0.000 (NA)
Eosinophils, Week 24, n=3,3,2,1	18.183 (31.4945)	-50.000 (66.1438)	50.000 (70.7107)	0.000 (NA)
Eosinophils, Week 28, n=3,2,2,1	44.950 (63.9644)	-87.500 (17.6777)	0.000 (141.4214)	0.000 (NA)
Eosinophils, Week 32, n=4,2,2,1	589.773 (1140.3590)	-25.000 (106.0660)	0.000 (141.4214)	-100.000 (NA)
Eosinophils, Week 36, n=3,1,2,1	13.890 (24.0582)	50.000 (NA)	0.000 (141.4214)	100.000 (NA)
Eosinophils, Week 40, n=1,1,1,1	100.000 (NA)	125.000 (NA)	100.000 (NA)	0.000 (NA)
Eosinophils, Week 44, n=1,1,1,0	0.000 (NA)	25.000 (NA)	100.000 (NA)
Eosinophils, Week 48, n=1,0,1,0	0.000 (NA)	200.000 (NA)
Eosinophils, Week 52, n=1,0,1,0	0.000 (NA)	300.000 (NA)
Eosinophils, Week 56, n=1,0,1,0	0.000 (NA)	200.000 (NA)
Eosinophils, Week 60, n=1,0,1,0	0.000 (NA)	200.000 (NA)
Eosinophils, Week 64, n=0,0,1,0	200.000 (NA)
Eosinophils, Week 72, n=0,0,1,0	100.000 (NA)
Eosinophils, Week 76, n=0,0,1,0	100.000 (NA)
Eosinophils, Week 80, n=0,0,1,0	200.000 (NA)
Eosinophils, Week 84, n=0,0,1,0	100.000 (NA)
Eosinophils, Week 88, n=0,0,1,0	100.000 (NA)
Hematocrit, Week 2, n=10,11,12,2	0.587 (6.3505)	1.183 (4.5122)	-0.387 (4.2431)	-1.480 (3.9739)
Hematocrit, Week 3, n=9,11,12,2	-1.006 (3.4842)	1.595 (4.8860)	0.138 (4.7403)	-4.355 (16.3412)
Hematocrit, Week 4, n=9,11,11,2	0.593 (3.8149)	0.292 (4.1522)	-1.677 (5.4977)	-7.650 (13.4633)
Hematocrit, Week 5, n=10,11,10,1	-1.018 (4.1817)	-1.864 (7.0759)	-0.131 (3.8130)	4.270 (NA)
Hematocrit, Week 8, n=9,10,10,1	0.604 (5.0812)	-0.771 (6.0100)	-0.511 (5.3238)	8.270 (NA)
Hematocrit, Week 12, n=6,10,7,1	1.648 (5.3385)	-2.580 (5.8249)	-18.046 (31.9934)	1.600 (NA)
Hematocrit, Week 16, n=7,8,4,1	-1.459 (5.9511)	-3.929 (6.5991)	-9.515 (9.0652)	1.330 (NA)
Hematocrit, Week 20, n=5,6,4,1	2.638 (6.8653)	-2.392 (7.0021)	-7.138 (7.7051)	0.000 (NA)
Hematocrit, Week 24, n=5,5,3,1	0.662 (8.0118)	-2.974 (8.6014)	-7.580 (7.0381)	2.130 (NA)
Hematocrit, Week 28, n=5,3,3,1	2.004 (5.2368)	-9.047 (17.3470)	-7.793 (10.5539)	3.470 (NA)
Hematocrit, Week 32, n=4,3,3,1	0.365 (9.8402)	-1.917 (4.8321)	-7.827 (12.0475)	-2.930 (NA)
Hematocrit, Week 36, n=3,1,3,1	1.320 (8.9495)	-16.070 (NA)	-3.420 (4.1589)	-8.800 (NA)
Hematocrit, Week 40, n=1,2,2,1	-4.780 (NA)	-7.755 (11.3632)	-21.690 (14.8068)	-10.130 (NA)
Hematocrit, Week 44, n=1,2,2,0	-4.070 (NA)	-1.650 (9.8146)	-8.725 (8.2944)
Hematocrit, Week 48, n=1,1,1,0	-4.070 (NA)	4.180 (NA)	-13.510 (NA)
Hematocrit, Week 52, n=1,1,1,0	-8.370 (NA)	-0.840 (NA)	-15.540 (NA)
Hematocrit, Week 56, n=1,1,1,0	-12.200 (NA)	3.060 (NA)	-18.920 (NA)
Hematocrit, Week 60, n=1,1,1,0	-7.420 (NA)	2.230 (NA)	-18.920 (NA)
Hematocrit, Week 64, n=1,1,1,0	-5.500 (NA)	-1.950 (NA)	-22.970 (NA)
Hematocrit, Week 68, n=1,0,1,0	-4.310 (NA)	-10.810 (NA)
Hematocrit, Week 72, n=0,0,1,0	-12.160 (NA)
Hematocrit, Week 76, n=0,0,1,0	-11.080 (NA)
Hematocrit, Week 80, n=0,0,1,0	-5.680 (NA)
Hematocrit, Week 84, n=0,0,1,0	1.890 (NA)
Hematocrit, Week 88, n=0,0,1,0	-4.320 (NA)
Hemoglobin, Week 2, n=11,11,12,2	1.513 (6.4384)	1.831 (4.2681)	0.216 (4.9536)	2.800 (3.9598)
Hemoglobin, Week 3, n=10,11,12,2	-1.144 (3.3900)	1.874 (5.1494)	-1.001 (4.4522)	-1.760 (11.5400)
Hemoglobin, Week 4, n=10,11,11,2	0.821 (3.7955)	0.564 (3.8663)	-1.301 (5.4112)	-6.225 (11.0662)
Hemoglobin, Week 5, n=10,11,10,1	-0.755 (4.7629)	-2.550 (6.7380)	0.889 (4.4094)	2.400 (NA)
Hemoglobin, Week 8, n=9,10,10,1	-0.313 (4.4329)	-1.203 (5.3379)	-0.633 (5.7100)	8.800 (NA)
Hemoglobin, Week 12, n=7,10,7,1	-0.121 (6.0781)	-3.316 (5.0843)	-4.847 (7.8349)	0.800 (NA)
Hemoglobin, Week 16, n=8,8,4,1	-4.005 (8.7693)	-4.451 (6.7484)	-12.315 (9.9652)	2.400 (NA)
Hemoglobin, Week 20, n=5,6,4,1	2.906 (8.7982)	-2.668 (7.5665)	-9.055 (9.7215)	1.600 (NA)
Hemoglobin, Week 24, n=5,5,3,1	2.148 (8.8710)	-4.124 (8.6379)	-10.137 (7.6478)	2.400 (NA)
Hemoglobin, Week 28, n=5,3,3,1	2.410 (6.9580)	-8.843 (21.8918)	-11.723 (11.7348)	4.800 (NA)
Hemoglobin, Week 32, n=4,3,3,1	2.838 (11.6934)	-3.430 (6.2333)	-11.350 (15.5425)	-4.000 (NA)
Hemoglobin, Week 36, n=3,1,3,1	4.303 (8.7527)	-22.030 (NA)	-5.893 (4.9326)	-12.800 (NA)
Hemoglobin, Week 40, n=1,2,2,1	-1.430 (NA)	-7.165 (12.6360)	-24.305 (17.7979)	-11.200 (NA)
Hemoglobin, Week 44, n=1,2,2,0	0.000 (NA)	-2.815 (13.9936)	-11.970 (12.0491)
Hemoglobin, Week 48, n=1,1,1,0	-2.140 (NA)	5.310 (NA)	-17.210 (NA)
Hemoglobin, Week 52, n=1,1,1,0	-5.710 (NA)	2.650 (NA)	-18.030 (NA)
Hemoglobin, Week 56, n=1,1,1,0	-10.000 (NA)	6.190 (NA)	-22.130 (NA)
Hemoglobin, Week 60, n=1,1,1,0	-5.710 (NA)	4.420 (NA)	-22.130 (NA)
Hemoglobin, Week 64, n=1,1,1,0	-2.860 (NA)	3.540 (NA)	-27.870 (NA)
Hemoglobin, Week 68, n=1,0,1,0	-2.140 (NA)	-15.570 (NA)
Hemoglobin, Week 72, n=0,0,1,0	-13.110 (NA)
Hemoglobin, Week 76, n=0,0,1,0	-13.110 (NA)
Hemoglobin, Week 80, n=0,0,1,0	-6.560 (NA)
Hemoglobin, Week 84, n=0,0,1,0	2.460 (NA)
Hemoglobin, Week 88, n=0,0,1,0	-4.100 (NA)
Lymphocytes, Week 2, n=10,9,9,2	13.128 (26.4961)	10.492 (24.1299)	6.557 (14.9900)	-1.110 (1.5698)
Lymphocytes, Week 3, n=9,9,11,2	12.964 (21.6078)	13.431 (42.8448)	-1.674 (23.4467)	-26.515 (13.9229)
Lymphocytes, Week 4, n=9,9,9,2	7.117 (28.8484)	8.342 (24.6388)	-10.698 (14.0883)	-11.665 (16.4968)
Lymphocytes, Week 5, n=8,7,9,1	8.680 (20.3405)	1.481 (24.0919)	-6.918 (18.1022)	0.000 (NA)
Lymphocytes, Week 8, n=7,8,8,1	2.766 (29.3215)	-0.436 (14.5663)	-0.731 (14.9131)	36.360 (NA)
Lymphocytes, Week 12, n=5,7,7,1	4.374 (31.7985)	4.237 (25.5117)	-5.857 (18.8992)	-18.180 (NA)
Lymphocytes, Week 16, n=6,5,4,1	5.980 (34.3145)	-3.418 (17.2124)	-14.440 (22.8645)	0.000 (NA)
Lymphocytes, Week 20, n=4,5,4,1	7.935 (23.3030)	4.286 (38.4387)	-22.278 (28.4912)	9.090 (NA)
Lymphocytes, Week 24, n=4,3,3,1	10.143 (32.9329)	6.063 (42.7487)	-10.130 (24.8888)	27.270 (NA)
Lymphocytes, Week 28, n=4,2,3,1	7.328 (15.4134)	-37.780 (25.1447)	-7.750 (22.4674)	36.360 (NA)
Lymphocytes, Week 32, n=3,2,3,1	-1.597 (30.4679)	-8.485 (16.2847)	-12.510 (27.7148)	27.270 (NA)
Lymphocytes, Week 36, n=3,1,3,1	18.913 (32.5921)	-24.240 (NA)	-2.037 (17.6391)	9.090 (NA)
Lymphocytes, Week 40, n=1,1,2,1	33.330 (NA)	-30.300 (NA)	-27.855 (11.1086)	0.000 (NA)
Lymphocytes, Week 44, n=1,1,2,0	-8.330 (NA)	-16.670 (NA)	-15.715 (8.0822)
Lymphocytes, Week 48, n=1,0,1,0	8.330 (NA)	-21.430 (NA)
Lymphocytes, Week 52, n=1,0,1,0	8.330 (NA)	-21.430 (NA)
Lymphocytes, Week 56, n=1,0,1,0	-16.670 (NA)	-28.570 (NA)
Lymphocytes, Week 60, n=1,0,1,0	83.330 (NA)	-28.570 (NA)
Lymphocytes, Week 64, n=0,0,1,0	-42.860 (NA)
Lymphocytes, Week 68, n=0,0,1,0	-35.710 (NA)
Lymphocytes, Week 72, n=0,0,1,0	-28.570 (NA)
Lymphocytes, Week 76, n=0,0,1,0	-42.860 (NA)
Lymphocytes, Week 80, n=0,0,1,0	-42.860 (NA)
Lymphocytes, Week 84, n=0,0,1,0	-21.430 (NA)
Lymphocytes, Week 88, n=0,0,1,0	-42.860 (NA)
MCH, Week 2, n= 11,11,12,2	0.360 (1.0203)	-0.477 (0.5538)	85.741 (294.1068)	1.020 (0.9334)
MCH, Week 3, n=10,11,12,2	-0.341 (1.7584)	-1.000 (1.2030)	15.582 (56.4264)	-0.310 (1.4566)
MCH, Week 4, n=10,11,11,2	0.042 (1.3267)	-0.942 (1.2281)	-0.277 (2.0468)	-0.735 (1.5203)
MCH, Week 5, n=10,11,10,1	-0.171 (1.5524)	-1.856 (1.4255)	0.395 (1.8147)	-0.670 (NA)
MCH, Week 8, n=9,10,10,1	-1.582 (2.0961)	18.355 (64.3175)	-1.095 (2.1396)	-0.340 (NA)
MCH, Week 12, n=7,10,7,1	-1.779 (0.8758)	-2.970 (2.2530)	-3.199 (3.6432)	-2.680 (NA)
MCH, Week 16, n=8,8,4,1	-2.315 (2.6806)	-2.759 (2.4800)	-6.200 (3.1007)	-1.680 (NA)
MCH, Week 20, n=5,6,4,1	-1.384 (3.1912)	-3.355 (3.6335)	-1.515 (3.7408)	-2.010 (NA)
MCH, Week 24, n=5,5,3,1	-0.228 (4.4495)	-4.376 (4.3285)	-6.213 (2.3011)	-4.360 (NA)
MCH, Week 28, n=5,3,3,1	-0.074 (4.0385)	-2.653 (6.3945)	-7.543 (4.5062)	-2.350 (NA)
MCH, Week 32, n=4,3,3,1	1.873 (4.2547)	-2.137 (4.9163)	-7.767 (5.6425)	-3.020 (NA)
MCH, Week 36, n=3,1,3,1	2.693 (2.3328)	-6.350 (NA)	-5.237 (1.9581)	-8.390 (NA)
MCH, Week 40, n=1,2,2,1	3.380 (NA)	-0.255 (2.4819)	-7.705 (3.3870)	-9.060 (NA)
MCH, Week 44, n=1,2,2,0	4.000 (NA)	-0.710 (0.0566)	-4.425 (1.8314)
MCH, Week 48, n=1,1,1,0	2.150 (NA)	-0.750 (NA)	-5.720 (NA)
MCH, Week 52, n=1,1,1,0	2.150 (NA)	1.500 (NA)	-6.060 (NA)
MCH, Week 56, n=1,1,1,0	-0.620 (NA)	-0.380 (NA)	-4.380 (NA)
MCH, Week 60, n=1,1,1,0	1.230 (NA)	1.130 (NA)	-4.380 (NA)
MCH, Week 64, n=1,1,1,0	0.920 (NA)	2.630 (NA)	-10.100 (NA)
MCH, Week 68, n=1,0,1,0	0.620 (NA)	-5.390 (NA)
MCH, Week 72, n=0,0,1,0	-4.710 (NA)
MCH, Week 76, n=0,0,1,0	-2.360 (NA)
MCH, Week 80, n=0,0,1,0	0.340 (NA)
MCH, Week 84, n=0,0,1,0	-1.010 (NA)
MCH, Week 88, n=0,0,1,0	1.680 (NA)
MCV, Week 2, n= 11,11,12,2	-0.425 (1.5619)	-0.915 (1.9177)	0.101 (2.0574)	-2.500 (1.9516)
MCV, Week 3, n=10,11,12,2	-0.735 (1.7112)	-1.025 (2.1801)	0.158 (1.9350)	-2.940 (4.1578)
MCV, Week 4, n=10,11,11,2	-0.376 (1.5149)	-0.868 (1.6593)	-0.749 (1.7087)	-2.100 (4.5538)
MCV, Week 5, n=10,11,10,1	-0.633 (1.8430)	-0.936 (1.6268)	-0.584 (1.4207)	1.120 (NA)
MCV, Week 8, n=9,10,10,1	-0.890 (1.7420)	-1.471 (2.3336)	-1.028 (1.2245)	0.000 (NA)
MCV, Week 12, n=7,10,7,1	-1.806 (1.5447)	-2.108 (2.4766)	-2.961 (2.6274)	-2.250 (NA)
MCV, Week 16, n=8,8,4,1	-1.353 (1.5169)	-2.014 (1.5731)	-3.160 (1.6961)	-2.250 (NA)
MCV, Week 20, n=5,6,4,1	-2.284 (1.5380)	-2.773 (2.6459)	-2.548 (1.4104)	-3.370 (NA)
MCV, Week 24, n=5,5,3,1	-2.180 (2.5123)	-2.976 (3.1047)	-3.273 (2.1356)	-4.490 (NA)
MCV, Week 28, n=5,3,3,1	-0.796 (1.9042)	-1.810 (1.9641)	-3.593 (2.6835)	-3.370 (NA)
MCV, Week 32, n=4,3,3,1	-0.243 (1.0303)	-0.250 (1.0672)	-3.913 (1.5369)	-1.120 (NA)
MCV, Week 36, n=3,1,3,1	-0.180 (1.3888)	0.770 (NA)	-2.397 (1.6820)	-4.490 (NA)
MCV, Week 40, n=1,2,2,1	-0.510 (NA)	-0.820 (1.1597)	-4.245 (1.6051)	-6.740 (NA)
MCV, Week 44, n=1,2,2,0	-0.310 (NA)	1.075 (4.2073)	-0.895 (3.3022)
MCV, Week 48, n=1,1,1,0	0.410 (NA)	-1.190 (NA)	-1.560 (NA)
MCV, Week 52, n=1,1,1,0	-1.130 (NA)	-1.430 (NA)	-3.440 (NA)
MCV, Week 56, n=1,1,1,0	-2.990 (NA)	-2.740 (NA)	-0.220 (NA)
MCV, Week 60, n=1,1,1,0	-0.720 (NA)	0.000 (NA)	-0.220 (NA)
MCV, Week 64, n=1,1,1,0	-1.850 (NA)	-2.260 (NA)	-3.780 (NA)
MCV, Week 68, n=1,0,1,0	-1.540 (NA)	0.220 (NA)
MCV, Week 72, n=0,0,1,0	-3.440 (NA)
MCV, Week 76, n=0,0,1,0	0.110 (NA)
MCV, Week 80, n=0,0,1,0	1.560 (NA)
MCV, Week 84, n=0,0,1,0	-1.440 (NA)
MCV, Week 88, n=0,0,1,0	1.670 (NA)
Monocytes, Week 2, n=10,9,9,2	5.541 (34.2863)	22.173 (60.1911)	-10.849 (24.6931)	-28.025 (16.9352)
Monocytes, Week 3, n=9,9,11,2	-0.646 (30.4427)	-0.434 (19.0109)	-12.739 (34.2922)	-28.025 (16.9352)
Monocytes, Week 4, n=9,9,9,2	1.097 (33.5523)	13.623 (49.8243)	-10.942 (28.2516)	-23.580 (5.0629)
Monocytes, Week 5, n=8,8,9,1	-5.118 (33.7156)	5.200 (56.5226)	2.906 (43.9084)	-20.000 (NA)
Monocytes, Week 8, n=7,8,9,1	7.991 (26.3341)	12.321 (53.9449)	-8.621 (36.1243)	-20.000 (NA)
Monocytes, Week 12, n=5,7,7,1	1.710 (23.3573)	17.299 (46.0764)	-0.061 (34.6523)	-20.000 (NA)
Monocytes, Week 16, n=6,5,4,1	11.403 (40.0796)	12.852 (51.7225)	0.638 (19.3854)	-20.000 (NA)
Monocytes, Week 20, n=4,5,4,1	1.918 (37.7552)	-2.744 (20.6555)	-23.258 (8.0211)	0.000 (NA)
Monocytes, Week 24, n=4,3,3,1	10.033 (44.7607)	30.770 (53.2952)	-20.633 (18.0268)	0.000 (NA)
Monocytes, Week 28, n=4,2,3,1	13.760 (32.3438)	0.000 (0.0000)	-9.523 (16.4949)	0.000 (NA)
Monocytes, Week 32, n=3,2,3,1	6.360 (48.8989)	43.845 (90.2905)	-25.397 (22.5044)	0.000 (NA)
Monocytes, Week 36, n=3,1,3,1	13.890 (34.6958)	50.000 (NA)	-14.287 (24.7452)	-20.000 (NA)
Monocytes, Week 40, n=1,1,2,1	0.000 (NA)	134.620 (NA)	-23.810 (13.4633)	-20.000 (NA)
Monocytes, Week 44, n=1,1,2,0	-25.000 (NA)	46.150 (NA)	-14.285 (20.2020)
Monocytes, Week 48, n=1,0,1,0	0.000 (NA)	-42.860 (NA)
Monocytes, Week 52, n=1,0,1,0	-25.000 (NA)	-14.290 (NA)
Monocytes, Week 56, n=1,0,1,0	25.000 (NA)	-14.290 (NA)
Monocytes, Week 60, n=1,0,1,0	25.000 (NA)	-14.290 (NA)
Monocytes, Week 64, n=0,0,1,0	-28.570 (NA)
Monocytes, Week 68, n=0,0,1,0	-28.570 (NA)
Monocytes, Week 72, n=0,0,1,0	-28.570 (NA)
Monocytes, Week 76, n=0,0,1,0	-42.860 (NA)
Monocytes, Week 80, n=0,0,1,0	-28.570 (NA)
Monocytes, Week 84, n=0,0,1,0	-14.290 (NA)
Monocytes, Week 88, n=0,0,1,0	-42.860 (NA)
Platelet count, Week 2, n=11,11,12,2	8.585 (15.9118)	14.016 (19.2876)	6.250 (13.3852)	16.390 (18.2434)
Platelet count, Week 3, n=10,11,12,2	-0.057 (12.3510)	5.440 (11.6551)	-1.445 (10.3439)	8.325 (15.3654)
Platelet count, Week 4, n=10,11,11,2	-0.921 (7.2065)	-4.057 (9.0344)	-8.287 (8.2288)	11.095 (7.1630)
Platelet count, Week 5, n=10,11,10,1	-4.600 (8.7256)	0.846 (24.9856)	-3.811 (11.4610)	18.180 (NA)
Platelet count, Week 8, n=9,10,10,1	2.416 (12.6516)	2.883 (9.9460)	2.206 (11.3950)	18.690 (NA)
Platelet count, Week 12, n=7, 9,7,1	6.046 (15.8538)	-3.291 (9.0120)	-1.393 (12.3185)	9.090 (NA)
Platelet count, Week 16, n=8,8,4,1	7.735 (21.7273)	-7.453 (10.0630)	2.405 (29.4379)	14.650 (NA)
Platelet count, Week 20, n=5,6,4,1	-3.764 (11.6336)	-5.373 (11.3944)	2.958 (22.8724)	14.140 (NA)
Platelet count, Week 24, n=5,5,3,1	0.846 (18.2657)	5.036 (21.6048)	-0.247 (28.6042)	23.740 (NA)
Platelet count, Week 28, n=5,3,3,1	-1.656 (13.0916)	-5.473 (16.0800)	-7.450 (17.5451)	17.680 (NA)
Platelet count, Week 32, n=4,3,3,1	-20.275 (52.6390)	-8.827 (11.3729)	0.790 (28.4249)	39.900 (NA)
Platelet count, Week 36, n=3,1,3,1	-2.597 (19.7730)	-8.820 (NA)	2.967 (18.8553)	50.000 (NA)
Platelet count, Week 40, n=1,2,2,1	9.630 (NA)	0.785 (4.2356)	-3.070 (23.6315)	57.580 (NA)
Platelet count, Week 44, n=1,2,2,0	0.460 (NA)	-25.160 (36.1756)	-9.450 (9.8571)
Platelet count, Week 48, n=1,1,1,0	-5.960 (NA)	-1.680 (NA)	-8.680 (NA)
Platelet count, Week 52, n=1,1,1,0	-2.750 (NA)	-10.080 (NA)	-1.650 (NA)
Platelet count, Week 56, n=1,1,1,0	0.920 (NA)	7.140 (NA)	-7.440 (NA)
Platelet count, Week 60, n=1,1,1,0	16.060 (NA)	0.000 (NA)	-7.440 (NA)
Platelet count, Week 64, n=1,1,1,0	-7.340 (NA)	-7.140 (NA)	-3.310 (NA)
Platelet count, Week 68, n=1,0,1,0	-0.460 (NA)	-11.570 (NA)
Platelet count, Week 72, n=0,0,1,0	-2.070 (NA)
Platelet count, Week 76, n=0,0,1,0	-26.860 (NA)
Platelet count, Week 80, n=0,0,1,0	-16.120 (NA)
Platelet count, Week 84, n=0,0,1,0	-16.120 (NA)
Platelet count, Week 88, n=0,0,1,0	-31.400 (NA)
Total Neutrophils, Week 2, n= 10,9,9,2	6.689 (45.0555)	-6.798 (37.2810)	-3.907 (19.8441)	0.380 (0.5374)
Total Neutrophils, Week 3, n=9,9,11,2	-1.933 (38.2961)	-9.604 (34.8399)	-1.496 (28.6849)	13.885 (25.0245)
Total Neutrophils, Week 4, n=9,9,9,2	-0.562 (48.2259)	10.019 (70.2338)	-17.251 (23.9291)	-14.600 (5.7558)
Total Neutrophils, Week 5, n=8,8,9,1	-14.485 (23.6250)	-10.721 (27.2234)	-3.097 (38.5928)	36.840 (NA)
Total Neutrophils, Week 8, n=7,8,9,1	-6.409 (22.6409)	-8.959 (32.9931)	-6.433 (31.7619)	47.370 (NA)
Total Neutrophils, Week 12, n=5,7,7,1	-7.292 (29.7757)	-4.930 (24.9495)	-0.051 (28.1875)	36.840 (NA)
Total Neutrophils, Week 16, n=6,5,4,1	-11.992 (26.9160)	-17.300 (32.1449)	-11.233 (29.4360)	0.000 (NA)
Total Neutrophils, Week 20, n=4,5,4,1	-8.668 (40.6758)	-22.398 (33.4115)	-37.638 (14.2156)	31.580 (NA)
Total Neutrophils, Week 24, n=4,3,3,1	-9.695 (39.8258)	537.517 (875.0638)	-25.860 (19.3876)	31.580 (NA)
Total Neutrophils, Week 28, n=4,1,3,1	-4.173 (38.7614)	-23.910 (NA)	-15.737 (30.5955)	-5.260 (NA)
Total Neutrophils, Week 32, n=3,2,3,1	-17.917 (30.8176)	43.785 (117.2595)	-27.140 (12.5575)	68.420 (NA)
Total Neutrophils, Week 36, n=3,1,3,1	-19.807 (28.6365)	-13.120 (NA)	-22.173 (19.2353)	47.370 (NA)
Total Neutrophils, Week 40, n=1,1,2,1	23.810 (NA)	57.920 (NA)	-18.750 (26.5165)	-5.260 (NA)
Total Neutrophils, Week 44, n=1,1,2,0	0.000 (NA)	1.810 (NA)	-15.130 (13.9583)
Total Neutrophils, Week 48, n=1,0,1,0	-14.290 (NA)	-23.680 (NA)
Total Neutrophils, Week 52, n=1,0,1,0	61.900 (NA)	0.000 (NA)
Total Neutrophils, Week 56, n=1,0,1,0	4.760 (NA)	-21.050 (NA)
Total Neutrophils, Week 60, n=1,0,1,0	33.330 (NA)	-21.050 (NA)
Total Neutrophils, Week 64, n=0,0,1,0	-13.160 (NA)
Total Neutrophils, Week 68, n=0,0,1,0	-15.790 (NA)
Total Neutrophils, Week 72, n=0,0,1,0	-21.050 (NA)
Total Neutrophils, Week 76, n=0,0,1,0	-39.470 (NA)
Total Neutrophils, Week 80, n=0,0,1,0	-15.790 (NA)
Total Neutrophils, Week 84, n=0,0,1,0	-21.050 (NA)
Total Neutrophils, Week 88, n=0,0,1,0	-28.950 (NA)
WBC count, Week 2, n=11,11,12,2	6.813 (29.4392)	-2.077 (26.5166)	0.445 (15.7801)	-2.220 (0.7920)
WBC count, Week 3, n=10,11,12,2	1.486 (24.4918)	-2.625 (26.9770)	-3.928 (20.8967)	-1.715 (6.3569)
WBC count, Week 4, n=10,11,11,2	-0.001 (28.4127)	5.575 (51.6285)	-12.681 (18.5282)	-12.505 (9.8217)
WBC count, Week 5, n=10,11,10,1	-4.419 (20.0450)	-10.823 (16.8580)	-3.190 (31.2346)	19.440 (NA)
WBC count, Week 8, n=9,10,10,1	-3.917 (18.3295)	-8.811 (23.2822)	-2.931 (23.8804)	30.560 (NA)
WBC count, Week 12, n=7,10,7,1	-1.723 (19.0232)	-10.782 (18.8356)	2.471 (25.2046)	8.330 (NA)
WBC count, Week 16, n=8,8,4,1	-4.974 (23.1270)	-16.450 (20.2532)	-11.380 (20.6158)	-2.780 (NA)
WBC count, Week 20, n=5,6,4,1	-3.674 (25.9508)	-15.540 (21.0813)	-30.808 (10.3805)	19.440 (NA)
WBC count, Week 24, n=5,5,3,1	-0.176 (33.0932)	2.760 (47.1809)	-23.037 (13.3905)	27.780 (NA)
WBC count, Week 28, n=5,3,3,1	3.036 (22.6756)	-10.843 (8.9673)	-15.997 (15.6148)	8.330 (NA)
WBC count, Week 32, n=4,3,3,1	-9.978 (22.7259)	14.077 (73.8998)	-24.583 (11.4453)	47.220 (NA)
WBC count, Week 36, n=3,1,3,1	-6.547 (29.9390)	-8.810 (NA)	-17.613 (6.2673)	27.780 (NA)
WBC count, Week 40, n=1,2,2,1	23.080 (NA)	21.725 (36.8756)	-22.375 (12.3532)	-5.560 (NA)
WBC count, Week 44, n=1,2,2,0	-7.690 (NA)	-2.525 (6.6822)	-17.225 (0.7849)
WBC count, Week 48, n=1,1,1,0	-5.130 (NA)	-18.840 (NA)	-25.760 (NA)
WBC count, Week 52, n=1,1,1,0	35.900 (NA)	-8.700 (NA)	-9.090 (NA)
WBC count, Week 56, n=1,1,1,0	-7.690 (NA)	-2.900 (NA)	-25.760 (NA)
WBC count, Week 60, n=1,1,1,0	43.590 (NA)	-10.140 (NA)	-25.760 (NA)
WBC count, Week 64, n=1,1,1,0	15.380 (NA)	-7.250 (NA)	-24.240 (NA)
WBC count, Week 68, n=1,0,1,0	-2.560 (NA)	-25.760 (NA)
WBC count, Week 72, n=0,0,1,0	-27.270 (NA)
WBC count, Week 76, n=0,0,1,0	-42.420 (NA)
WBC count, Week 80, n=0,0,1,0	-27.270 (NA)
WBC count, Week 84, n=0,0,1,0	-24.240 (NA)
WBC count, Week 88, n=0,0,1,0	-36.360 (NA)

5. Primary Outcome

Title	Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: International Normalized Ratio (INR), Prothrombin Time (PT), Partial Thromboplastin Time (PTT)
Description	Blood samples were collected to analyze the hematology parameters: INR, PT and PTT. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Time Frame	Baseline (Day 1), Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	10	9	11	1
INR, n=9,9,11,1	-9.266 (31.1026)	1.230 (3.7353)	0.287 (0.6848)	11.110 (NA)
PT, n=9,9,11,0	114.626 (344.5226)	-0.677 (5.5257)	1.328 (1.9928)
PTT, n=10,9,11,0	252.137 (799.4078)	3.480 (11.0842)	4.596 (4.3461)

6. Primary Outcome

Title	Percent Change From Baseline in Chemistry Parameters in Combination Treatment Period:ALT, Albumin, ALP, AST, Calcium, CO2, Chloride, Creatinine, Direct Bilirubin, Glucose, Lactate Dehydrogenase, Magnesium, Potassium, Sodium, Total Bilirubin, Total Protein
Description	Blood samples were collected to analyze the chemistry parameters: ALT, Albumin, Alkaline phosphatase (ALP), Aspartate amino transferase (AST), Calcium, Carbon dioxide (CO2), Chloride, Creatinine, Direct bilirubin, Glucose, Lactate dehydrogenase, Magnesium, Potassium, Sodium, Total bilirubin and Total protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Time Frame	Baseline (Day 1), Weeks 1,2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	2
ALT:Week 1, n=0,0,3,1	19.283 (22.1495)	42.860 (NA)
ALT:Week 2, n=11,11,12,2	24.745 (33.0344)	26.454 (40.8793)	37.503 (19.7223)	35.715 (10.1046)
ALT:Week 3, n=10,11,12,2	23.264 (31.2843)	32.356 (43.4898)	30.123 (16.5230)	14.285 (20.2020)
ALT:Week 4, n=10,11,11,2	29.468 (30.6030)	42.434 (57.8048)	58.457 (62.8020)	28.575 (20.2020)
ALT:Week 5, n= 10,11,10,1	29.714 (30.3371)	45.801 (36.5261)	39.647 (33.2853)	28.570 (NA)
ALT:Week 8, n=9,10,10,1	53.636 (62.0500)	57.566 (61.0093)	32.372 (26.1619)	14.290 (NA)
ALT:Week 12, n=7,10,7,1	31.460 (37.8221)	45.549 (37.9079)	21.621 (22.5414)	28.570 (NA)
ALT:Week 16, n=8,8,4,1	30.841 (36.3547)	37.271 (41.2228)	25.113 (50.7297)	57.140 (NA)
ALT:Week 20, n=5,6,4,1	31.442 (28.4784)	17.172 (47.1226)	19.048 (26.0889)	42.860 (NA)
ALT:Week 24, n=5,5,3,1	25.280 (29.7220)	23.628 (56.9181)	26.863 (9.1878)	57.140 (NA)
ALT:Week 28, n=5,4,3,1	48.140 (25.3878)	-15.128 (35.7843)	9.793 (10.6010)	57.140 (NA)
ALT:Week 32, n=4,3,3,1	44.170 (29.4179)	-31.510 (5.3476)	7.970 (11.6457)	42.860 (NA)
ALT:Week 36, n=3,1,3,1	53.580 (26.3536)	-6.670 (NA)	3.180 (11.3589)	-14.290 (NA)
ALT:Week 40, n=1,2,2,1	0.000 (NA)	-27.060 (0.5515)	-0.495 (8.1388)	14.290 (NA)
ALT:Week 44, n=1,2,2,0	50.000 (NA)	6.075 (66.8287)	-3.125 (4.4194)
ALT:Week 48, n=1,1,1,0	100.000 (NA)	-19.610 (NA)	15.790 (NA)
ALT:Week 52, n=1,1,1,0	50.000 (NA)	-43.140 (NA)	0.000 (NA)
ALT:Week 56, n=1,1,1,0	0.000 (NA)	-47.060 (NA)	-5.260 (NA)
ALT:Week 60, n=1,1,1,0	25.000 (NA)	-33.330 (NA)	15.790 (NA)
ALT:Week 64, n=1,1,1,0	50.000 (NA)	-49.020 (NA)	15.790 (NA)
ALT:Week 68, n=1,0,1,0	0.000 (NA)	26.320 (NA)
ALT:Week 72, n=0,0,1,0	42.110 (NA)
ALT:Week 76, n=0,0,1,0	-15.790 (NA)
ALT:Week 80, n=0,0,1,0	10.530 (NA)
ALT:Week 84, n=0,0,1,0	-5.260 (NA)
ALT:Week 88, n=0,0,1,0	5.260 (NA)
Albumin:Week 1, n=0,0,3,1	1.450 (2.5115)	0.000 (NA)
Albumin:Week 2, n=11,11,12,2	1.895 (7.5980)	-2.445 (5.0415)	0.137 (6.3551)	-3.230 (10.7197)
Albumin:Week 3, n=10,11,12,2	0.642 (7.8696)	-1.401 (5.7148)	-2.284 (11.8853)	-5.670 (11.0874)
Albumin:Week 4, n=10,11,11,2	2.024 (3.2354)	-1.667 (3.7915)	-1.075 (4.8150)	-8.665 (3.0335)
Albumin:Week 5, n= 10,11,10,1	0.625 (5.4575)	-0.532 (4.3994)	0.597 (5.0133)	0.000 (NA)
Albumin:Week 8, n=9,10,10,1	3.182 (3.5152)	-2.282 (3.3157)	1.648 (6.0048)	10.870 (NA)
Albumin:Week 12, n=6,10,7,1	1.805 (7.7531)	-4.026 (5.6375)	0.547 (4.3503)	-2.170 (NA)
Albumin:Week 16, n=8,8,4,1	0.755 (6.1997)	-4.880 (4.0347)	-3.378 (5.6123)	2.170 (NA)
Albumin:Week 20, n=5,6,4,1	0.596 (10.1128)	-3.827 (6.8293)	0.130 (6.2519)	2.170 (NA)
Albumin:Week 24, n=5,5,3,1	1.070 (5.9309)	-4.052 (4.0523)	-1.130 (3.9870)	4.350 (NA)
Albumin:Week 28, n=5,4,3,1	0.668 (5.4560)	-8.870 (8.1232)	1.147 (5.8101)	2.170 (NA)
Albumin:Week 32, n=4,3,3,1	3.635 (8.4967)	-5.747 (4.0772)	-3.603 (7.9065)	-4.350 (NA)
Albumin:Week 36, n=3,1,3,1	2.403 (4.6570)	-9.300 (NA)	-1.180 (5.0541)	-2.170 (NA)
Albumin:Week 40, n=1,2,2,1	-9.300 (NA)	-4.650 (9.8712)	-7.730 (4.7800)	2.170 (NA)
Albumin:Week 44, n=1,2,2,0	-4.650 (NA)	-3.490 (4.9356)	-0.905 (10.5005)
Albumin:Week 48, n=1,1,1,0	-4.650 (NA)	2.330 (NA)	-8.330 (NA)
Albumin:Week 52, n=1,1,1,0	-6.980 (NA)	-6.980 (NA)	-8.330 (NA)
Albumin:Week 56, n=1,1,1,0	-9.300 (NA)	-6.980 (NA)	-8.330 (NA)
Albumin:Week 60, n=1,1,1,0	-9.300 (NA)	-4.650 (NA)	-11.110 (NA)
Albumin:Week 64, n=1,1,1,0	-6.980 (NA)	-2.330 (NA)	-8.330 (NA)
Albumin:Week 68, n=1,0,1,0	-6.980 (NA)	-5.560 (NA)
Albumin:Week 72, n=0,0,1,0	-8.330 (NA)
Albumin:Week 76, n=0,0,1,0	-11.110 (NA)
Albumin:Week 80, n=0,0,1,0	0.000 (NA)
Albumin:Week 84, n=0,0,1,0	-2.780 (NA)
Albumin:Week 88, n=0,0,1,0	-13.890 (NA)
ALP:Week 1, n=0,0,3,1	-4.147 (6.3515)	-5.410 (NA)
ALP:Week 2, n=11,10,12,2	3.165 (15.9188)	2.881 (13.4737)	2.665 (19.2406)	-3.660 (16.4897)
ALP:Week 3, n=10,10,12,2	6.972 (10.8810)	5.072 (17.3872)	-0.942 (15.7497)	10.000 (14.1421)
ALP:Week 4, n=10,10,11,2	3.496 (11.7663)	11.790 (21.9785)	-2.819 (16.9420)	21.665 (16.4968)
ALP:Week 5, n=10,11,10,1	3.251 (14.5791)	11.901 (20.1563)	0.269 (17.4773)	8.000 (NA)
ALP:Week 8, n=9,10,10,1	4.360 (12.8823)	12.790 (27.1346)	-1.651 (18.0020)	28.000 (NA)
ALP:Week 12, n=7,10,7,1	1.306 (18.5543)	11.758 (37.2451)	-3.350 (17.4644)	6.000 (NA)
ALP:Week 16, n=8,8,4,1	2.364 (35.6322)	18.066 (54.1061)	-10.875 (7.5274)	22.000 (NA)
ALP:Week 20, n=5,6,4,1	-19.620 (7.2268)	25.492 (87.1563)	-13.655 (8.0427)	18.000 (NA)
ALP:Week 24, n=5,5,3,1	-20.088 (8.7955)	71.670 (167.7482)	-18.933 (5.0374)	16.000 (NA)
ALP:Week 28, n=5,4,3,1	-15.240 (11.3616)	75.765 (161.7779)	-16.040 (11.2100)	14.000 (NA)
ALP:Week 32, n=4,3,3,1	-16.640 (11.5509)	84.763 (119.3992)	-10.653 (22.0605)	38.000 (NA)
ALP:Week 36, n=3,1,3,1	-9.937 (4.2691)	173.030 (NA)	-9.480 (18.9095)	24.000 (NA)
ALP:Week 40, n=1,2,2,1	-3.850 (NA)	24.230 (59.4818)	-20.895 (0.1485)	12.000 (NA)
ALP:Week 44, n=1,2,2,0	5.770 (NA)	51.715 (133.4381)	-14.000 (19.7990)
ALP:Week 48, n=1,1,1,0	1.920 (NA)	-29.460 (NA)	-21.000 (NA)
ALP:Week 52, n=1,1,1,0	9.620 (NA)	-44.190 (NA)	-15.000 (NA)
ALP:Week 56, n=1,1,1,0	1.920 (NA)	-41.090 (NA)	-10.000 (NA)
ALP:Week 60, n=1,1,1,0	-15.380 (NA)	-24.810 (NA)	-8.000 (NA)
ALP:Week 64, n=1,1,1,0	-19.230 (NA)	-37.980 (NA)	-11.000 (NA)
ALP:Week 68, n=1,0,1,0	-9.620 (NA)	-12.000 (NA)
ALP:Week 72, n=0,0,1,0	-13.000 (NA)
ALP:Week 76, n=0,0,1,0	-26.000 (NA)
ALP:Week 80, n=0,0,1,0	-14.000 (NA)
ALP:Week 84, n=0,0,1,0	-9.000 (NA)
ALP:Week 88, n=0,0,1,0	-3.000 (NA)
AST:Week 1, n=0,0,3,1	17.083 (4.0182)	27.780 (NA)
AST:Week 2, n=11,11,12,1	15.050 (26.7980)	10.286 (21.5863)	18.918 (29.8292)	11.110 (NA)
AST:Week 3, n=10,11,12,1	8.979 (17.9450)	6.365 (20.9402)	9.471 (29.6507)	-5.560 (NA)
AST:Week 4, n=10,11,11,1	10.427 (13.4082)	24.937 (41.2658)	8.762 (32.5615)	22.220 (NA)
AST:Week 5, n=10,11,10,0	7.934 (22.4691)	31.374 (27.5174)	13.756 (38.8757)
AST:Week 8, n=9,10,10,0	33.676 (31.1394)	25.584 (65.6073)	11.455 (21.3067)
AST:Week 12, n=7,10,7,0	16.030 (15.7802)	29.940 (33.2473)	27.560 (28.1989)
AST:Week 16, n=8,8,4,0	31.790 (33.3934)	21.604 (29.1979)	32.398 (52.6950)
AST:Week 20, n=5,6,4,0	13.548 (8.4530)	3.055 (33.4592)	23.855 (14.8504)
AST:Week 24, n=5,5,3,0	14.364 (11.9664)	9.360 (38.6693)	6.807 (32.9686)
AST:Week 28, n=5,4,3,0	23.032 (18.8242)	-12.230 (25.1693)	15.000 (13.2288)
AST:Week 32, n=4,3,3,0	17.590 (14.7541)	-39.743 (7.1666)	26.943 (30.4636)
AST:Week 36, n=3,1,3,0	23.717 (4.7627)	-5.000 (NA)	13.193 (27.9755)
AST:Week 40, n=1,2,2,0	35.290 (NA)	-12.060 (25.3710)	-2.085 (14.7290)
AST:Week 44, n=1,2,2,0	23.530 (NA)	2.060 (46.5842)	6.250 (26.5165)
AST:Week 48, n=1,1,1,0	35.290 (NA)	-29.410 (NA)	-18.750 (NA)
AST:Week 52, n=1,1,1,0	11.760 (NA)	-50.000 (NA)	-25.000 (NA)
AST:Week 56, n=1,1,1,0	17.650 (NA)	-50.000 (NA)	-18.750 (NA)
AST:Week 60, n=1,1,1,0	11.760 (NA)	-39.710 (NA)	-12.500 (NA)
AST:Week 64, n=1,1,1,0	58.820 (NA)	-57.350 (NA)	0.000 (NA)
AST:Week 68, n=1,0,1,0	47.060 (NA)	0.000 (NA)
AST:Week 72, n=0,0,1,0	0.000 (NA)
AST:Week 76, n=0,0,1,0	-31.250 (NA)
AST:Week 80, n=0,0,1,0	12.500 (NA)
AST:Week 84, n=0,0,1,0	-18.750 (NA)
AST:Week 88, n=0,0,1,0	-18.750 (NA)
Calcium:Week 1, n=0,0,3,1	-5.307 (1.8287)	-3.530 (NA)
Calcium:Week 2, n=11,11,12,2	-4.765 (6.1486)	-3.451 (4.2733)	-8.617 (6.2882)	-5.240 (9.2207)
Calcium:Week 3, n=10,11,12,2	-4.547 (7.2916)	-1.819 (3.4578)	-4.798 (3.5578)	-1.830 (7.3963)
Calcium:Week 4, n=10,10,11,2	-4.768 (5.4864)	-2.178 (5.4456)	-6.373 (4.8535)	-6.960 (13.4492)
Calcium:Week 5, n=10,11,10,1	-5.613 (4.6806)	-1.622 (5.5177)	-4.908 (4.6481)	3.400 (NA)
Calcium:Week 8, n=9,10,10,1	-5.359 (3.8797)	-2.750 (3.5749)	-4.512 (3.8618)	2.980 (NA)
Calcium:Week 12, n=6,10,7,1	-3.578 (5.6792)	-2.962 (2.8943)	-6.034 (5.0312)	0.000 (NA)
Calcium:Week 16, n=8,8,4,1	-4.259 (4.3485)	-4.580 (3.6844)	-6.105 (3.9821)	1.700 (NA)
Calcium:Week 20, n=5,6,4,1	-5.090 (5.8459)	0.690 (4.7342)	-5.103 (3.7503)	1.280 (NA)
Calcium:Week 24, n=5,5,3,1	-3.500 (2.1050)	-2.694 (1.8159)	-5.127 (4.9099)	5.110 (NA)
Calcium:Week 28, n=5,4,3,1	-2.380 (2.0033)	-3.428 (4.0359)	-5.423 (6.4883)	5.530 (NA)
Calcium:Week 32, n=4,3,3,1	-4.595 (3.5314)	-0.747 (2.2739)	-6.553 (5.6435)	1.280 (NA)
Calcium:Week 36, n=3,1,3,1	-5.473 (3.5181)	0.000 (NA)	-5.210 (5.7373)	0.000 (NA)
Calcium:Week 40, n=1,1,2,1	0.000 (NA)	-4.400 (NA)	-8.275 (11.1086)	2.130 (NA)
Calcium:Week 44, n=1,2,2,0	0.000 (NA)	2.075 (7.6014)	-1.760 (9.6732)
Calcium:Week 48, n=1,1,1,0	-8.160 (NA)	0.000 (NA)	-6.450 (NA)
Calcium:Week 52, n=1,1,1,0	-1.020 (NA)	2.130 (NA)	-8.600 (NA)
Calcium:Week 56, n=1,1,1,0	-7.140 (NA)	0.000 (NA)	-15.050 (NA)
Calcium:Week 60, n=1,1,1,0	-5.100 (NA)	-1.060 (NA)	-11.830 (NA)
Calcium:Week 64, n=1,1,1,0	-5.100 (NA)	1.060 (NA)	-10.750 (NA)
Calcium:Week 68, n=1,0,1,0	-2.040 (NA)	-8.600 (NA)
Calcium:Week 72, n=0,0,1,0	-7.530 (NA)
Calcium:Week 76, n=0,0,1,0	-11.830 (NA)
Calcium:Week 80, n=0,0,1,0	-10.750 (NA)
Calcium:Week 84, n=0,0,1,0	-6.450 (NA)
Calcium:Week 88, n=0,0,1,0	-11.830 (NA)
CO2:Week 1, n=0,0,3,1	-4.130 (7.0589)	-4.170 (NA)
CO2:Week 2, n=11,11,12,2	-7.175 (5.9450)	-1.014 (9.8790)	0.698 (4.2233)	-8.330 (17.6777)
CO2:Week 3, n=10,11,12,2	-5.396 (8.3219)	-0.359 (9.4162)	3.494 (8.5276)	4.165 (11.7875)
CO2:Week 4, n=10,11,11,2	-4.261 (6.6572)	-0.885 (8.7334)	1.185 (6.3365)	6.250 (2.9416)
CO2:Week 5, n=10,11,10,1	-6.484 (6.1629)	-0.911 (13.3754)	-1.661 (7.0570)	8.330 (NA)
CO2:Week 8, n=9,10,9,0	-6.336 (7.2636)	2.039 (9.9294)	2.270 (6.9135)
CO2:Week 12, n=6,10,7,0	-4.483 (11.0452)	0.176 (8.2049)	-1.396 (7.6354)
CO2:Week 16, n=8,8,4,0	-3.400 (5.6016)	-0.616 (11.9261)	-5.348 (3.8920)
CO2:Week 20, n=5,6,4,0	-1.334 (2.9829)	2.323 (11.0928)	0.200 (4.9861)
CO2:Week 24, n=5,5,3,1	-2.548 (8.4654)	-0.350 (10.9158)	-2.617 (2.2673)	4.170 (NA)
CO2:Week 28, n=5,4,3,1	0.454 (8.9936)	1.625 (9.1644)	0.050 (3.9252)	8.330 (NA)
CO2:Week 32, n=4,3,3,1	-3.868 (9.1162)	-3.570 (3.5700)	6.513 (5.9119)	12.500 (NA)
CO2:Week 36, n=3,1,3,1	0.277 (19.0084)	0.000 (NA)	1.230 (5.9413)	0.000 (NA)
CO2:Week 40, n=1,2,2,1	3.330 (NA)	0.000 (5.0487)	9.000 (1.4142)	-4.170 (NA)
CO2:Week 44, n=1,2,2,0	-6.670 (NA)	3.570 (5.0487)	2.000 (2.8284)
CO2:Week 48, n=1,1,1,0	-3.330 (NA)	-3.570 (NA)	0.000 (NA)
CO2:Week 52, n=1,1,1,0	6.670 (NA)	3.570 (NA)	0.000 (NA)
CO2:Week 56, n=1,1,1,0	0.000 (NA)	14.290 (NA)	0.000 (NA)
CO2:Week 60, n=1,1,1,0	-13.330 (NA)	0.000 (NA)	0.000 (NA)
CO2:Week 64, n=1,1,1,0	-6.670 (NA)	-10.710 (NA)	0.000 (NA)
CO2:Week 68, n=1,0,1,0	-3.330 (NA)	15.000 (NA)
CO2:Week 72, n=0,0,1,0	5.000 (NA)
CO2:Week 76, n=0,0,1,0	5.000 (NA)
CO2:Week 80, n=0,0,1,0	20.000 (NA)
CO2:Week 84, n=0,0,1,0	15.000 (NA)
CO2:Week 88, n=0,0,1,0	-10.000 (NA)
Chloride:Week 1, n=0,0,3,1	0.000 (1.9600)	4.000 (NA)
Chloride:Week 2, n=11,11,12,1	1.285 (2.5760)	1.720 (2.0330)	0.278 (2.1853)	-1.000 (NA)
Chloride:Week 3, n=10,11,12,1	1.110 (3.1963)	2.169 (1.5618)	1.042 (1.6055)	1.000 (NA)
Chloride:Week 4, n=10,11,11,1	1.786 (1.2600)	1.259 (1.9801)	0.270 (1.2350)	2.000 (NA)
Chloride:Week 5, n=10,11,10,0	1.038 (3.8548)	0.825 (2.3370)	-0.495 (2.5736)
Chloride:Week 8, n=9,10,10,0	1.342 (1.8157)	0.514 (2.3134)	-1.613 (2.5122)
Chloride:Week 12, n=5,10,7,0	2.218 (2.8158)	1.564 (2.1107)	-1.077 (1.4931)
Chloride:Week 16, n=8,8,4,0	1.379 (2.5654)	1.979 (1.6634)	-0.755 (2.3017)
Chloride:Week 20, n=5,6,4,0	1.818 (3.2011)	2.842 (2.1684)	0.470 (1.2655)
Chloride:Week 24, n=5,5,3,0	1.016 (2.5283)	0.204 (2.6191)	-0.590 (1.9337)
Chloride:Week 28, n=5,4,3,0	2.012 (1.2468)	1.515 (1.3092)	0.050 (1.6282)
Chloride:Week 32, n=4,3,3,0	2.230 (0.4359)	2.027 (2.0200)	-0.377 (1.9704)
Chloride:Week 36, n=3,1,3,0	1.703 (1.5832)	1.020 (NA)	1.283 (2.0455)
Chloride:Week 40, n=1,2,2,0	2.970 (NA)	-2.560 (6.4771)	-0.500 (0.7071)
Chloride:Week 44, n=1,2,2,0	1.980 (NA)	1.525 (0.7283)	0.460 (0.6505)
Chloride:Week 48, n=1,1,1,0	3.960 (NA)	3.030 (NA)	0.000 (NA)
Chloride:Week 52, n=1,1,1,0	0.990 (NA)	3.030 (NA)	0.000 (NA)
Chloride:Week 56, n=1,1,1,0	2.970 (NA)	-1.010 (NA)	1.830 (NA)
Chloride:Week 60, n=1,1,1,0	5.940 (NA)	-1.010 (NA)	0.920 (NA)
Chloride:Week 64, n=1,1,1,0	3.960 (NA)	4.040 (NA)	-0.920 (NA)
Chloride:Week 68, n=1,0,1,0	4.950 (NA)	0.000 (NA)
Chloride:Week 72, n=0,0,1,0	-0.920 (NA)
Chloride:Week 76, n=0,0,1,0	1.830 (NA)
Chloride:Week 80, n=0,0,1,0	-0.920 (NA)
Chloride:Week 84, n=0,0,1,0	-1.830 (NA)
Chloride:Week 88, n=0,0,1,0	0.000 (NA)
Creatinine:Week 1, n=0,0,3,1	2.337 (0.9935)	12.820 (NA)
Creatinine:Week 2, n=10,11,12,2	13.449 (12.6365)	2.836 (13.7885)	28.843 (62.8444)	184.385 (248.7248)
Creatinine:Week 3, n=10,11,12,2	3.530 (6.0391)	3.155 (12.3738)	12.522 (28.5284)	10.465 (8.7752)
Creatinine:Week 4, n=10,11,11,2	5.263 (13.2032)	-0.156 (11.9252)	11.198 (29.2772)	6.955 (17.3595)
Creatinine:Week 5, n=10,11,10,1	10.460 (13.3237)	-0.302 (13.6521)	7.088 (13.6665)	-8.510 (NA)
Creatinine:Week 8, n=9,10,10,1	4.977 (8.1992)	-4.440 (10.4367)	4.750 (7.8635)	-15.960 (NA)
Creatinine:Week 12, n=7,10,7,1	13.411 (24.2292)	-1.289 (11.0396)	2.236 (6.1696)	-13.830 (NA)
Creatinine:Week 16, n=8,8,4,1	7.920 (16.3323)	-5.519 (12.7681)	2.875 (5.2082)	-6.380 (NA)
Creatinine:Week 20, n=5,6,4,1	8.414 (5.0623)	-3.007 (13.8034)	10.315 (5.7571)	-2.130 (NA)
Creatinine:Week 24, n=5,5,3,1	14.184 (9.4608)	-11.006 (15.9134)	4.737 (4.2811)	-5.320 (NA)
Creatinine:Week 28, n=5,4,3,1	12.888 (6.5007)	-12.093 (14.6604)	2.520 (8.4940)	-1.060 (NA)
Creatinine:Week 32, n=4,3,3,1	11.690 (5.1478)	-17.913 (11.8535)	11.320 (14.2430)	-7.450 (NA)
Creatinine:Week 36, n=3,1,3,1	10.500 (5.7663)	-30.530 (NA)	-25.153 (53.5998)	-18.090 (NA)
Creatinine:Week 40, n=1,2,2,1	20.000 (NA)	-13.230 (27.4357)	-0.245 (2.0294)	-12.770 (NA)
Creatinine:Week 44, n=1,2,2,0	-6.000 (NA)	-13.775 (17.7413)	8.470 (4.8508)
Creatinine:Week 48, n=1,1,1,0	6.000 (NA)	-12.960 (NA)	-10.080 (NA)
Creatinine:Week 52, n=1,1,1,0	7.000 (NA)	-1.230 (NA)	1.680 (NA)
Creatinine:Week 56, n=1,1,1,0	-1.000 (NA)	-7.410 (NA)	9.240 (NA)
Creatinine:Week 60, n=1,1,1,0	15.000 (NA)	-8.020 (NA)	7.560 (NA)
Creatinine:Week 64, n=1,1,1,0	5.000 (NA)	29.630 (NA)	-2.520 (NA)
Creatinine:Week 68, n=1,0,1,0	-2.000 (NA)	-0.840 (NA)
Creatinine:Week 72, n=0,0,1,0	0.840 (NA)
Creatinine:Week 76, n=0,0,1,0	-8.400 (NA)
Creatinine:Week 80, n=0,0,1,0	-0.840 (NA)
Creatinine:Week 84, n=0,0,1,0	-0.840 (NA)
Creatinine:Week 88, n=0,0,1,0	-13.450 (NA)
Direct bilirubin:Week 1, n=0,0,1,0	0.000 (NA)
Direct bilirubin:Week 2, n=4,4,6,1	6.250 (65.7489)	-11.668 (23.3350)	-16.538 (40.5105)	0.000 (NA)
Direct bilirubin:Week 3, n=3,2,6,1	-16.667 (28.8675)	0.000 (0.0000)	-16.538 (40.5105)	0.000 (NA)
Direct bilirubin:Week 4, n=3,6,6,1	-16.667 (28.8675)	3.333 (32.0416)	0.128 (63.0024)	0.000 (NA)
Direct bilirubin:Week 5, n=3,6,5,0	-33.333 (28.8675)	-8.888 (14.4005)	-19.846 (44.3770)
Direct bilirubin:Week 8, n=3,5,4,0	-33.333 (38.1881)	76.000 (133.7161)	25.000 (50.0000)
Direct bilirubin:Week 12, n=1,5,3,0	0.000 (NA)	60.000 (134.1641)	0.257 (99.6152)
Direct bilirubin:Week 16, n=2,4,2,0	-50.000 (35.3553)	20.000 (54.1603)	-49.615 (70.1662)
Direct bilirubin:Week 20, n=0,2,1,0	0.000 (0.0000)	0.000 (NA)
Direct bilirubin:Week 24, n=0,3,1,0	-13.333 (23.0940)	-99.230 (NA)
Direct bilirubin:Week 28, n=0,1,1,0	0.000 (NA)	-99.230 (NA)
Direct bilirubin:Week 32, n=0,2,1,0	-10.000 (14.1421)	-99.230 (NA)
Direct bilirubin:Week 36, n=0,1,1,0	0.000 (NA)	-99.230 (NA)
Direct bilirubin:Week 40, n=0,2,0,0	-10.000 (14.1421)
Direct bilirubin:Week 44, n=0,1,0,0	0.000 (NA)
Direct bilirubin:Week 48, n=0,1,0,0	-20.000 (NA)
Direct bilirubin:Week 56, n=0,1,1,0	-80.000 (NA)	-99.230 (NA)
Direct bilirubin:Week 60, n=0,0,1,0	-99.230 (NA)
Direct bilirubin:Week 64, n=0,0,1,0	-99.230 (NA)
Direct bilirubin:Week 68, n=0,0,1,0	-99.230 (NA)
Direct bilirubin:Week 76, n=0,0,1,0	-99.230 (NA)
Direct bilirubin:Week 80, n=0,0,1,0	-99.230 (NA)
Direct bilirubin:Week 84, n=0,0,1,0	-99.230 (NA)
Direct bilirubin:Week 88, n=0,0,1,0	-99.230 (NA)
Glucose:Week 1, n=0,0,2,1	25.745 (36.4089)	40.630 (NA)
Glucose:Week 2, n=11,10,12,2	-11.921 (14.9844)	1.494 (21.6112)	-0.500 (13.1110)	8.005 (4.8861)
Glucose:Week 3, n=10,10,11,2	-4.956 (15.0667)	1.229 (19.6823)	2.856 (23.3024)	35.985 (3.7547)
Glucose:Week 4, n=9,10,10,2	-5.273 (9.5191)	4.053 (31.5693)	-0.019 (11.9348)	17.190 (11.0450)
Glucose:Week 5, n=9,11,9,0	-2.012 (6.5775)	-2.482 (15.7553)	1.737 (11.7985)
Glucose:Week 8, n=9,10,9,0	-5.971 (8.3770)	-4.807 (11.4303)	-2.250 (8.1208)
Glucose:Week 12, n=6,10,7,1	-4.812 (6.3454)	-3.481 (19.7216)	2.353 (6.2058)	18.180 (NA)
Glucose:Week 16, n=8,8,4,1	-2.948 (8.0302)	-5.276 (10.6100)	2.220 (10.1362)	15.910 (NA)
Glucose:Week 20, n=5,6,4,1	2.184 (7.8557)	0.290 (29.4058)	-4.715 (17.9623)	13.640 (NA)
Glucose:Week 24, n=5,5,3,1	-4.902 (14.4657)	3.640 (22.3870)	3.997 (9.6952)	9.090 (NA)
Glucose:Week 28, n=5,4,3,1	-0.288 (12.2744)	11.950 (23.9058)	3.610 (8.7790)	9.090 (NA)
Glucose:Week 32, n=4,3,3,1	3.148 (21.6666)	-13.227 (15.6650)	0.363 (2.7655)	2.270 (NA)
Glucose:Week 36, n=3,1,3,1	0.247 (4.2508)	20.620 (NA)	3.320 (9.2103)	13.640 (NA)
Glucose:Week 40, n=1,1,2,1	18.180 (NA)	-10.310 (NA)	3.485 (8.9308)	22.730 (NA)
Glucose:Week 44, n=1,2,2,0	17.170 (NA)	-7.955 (6.2438)	3.485 (8.9308)
Glucose:Week 48, n=1,1,1,0	13.130 (NA)	-10.620 (NA)	-2.830 (NA)
Glucose:Week 52, n=1,1,1,0	7.070 (NA)	-3.540 (NA)	2.830 (NA)
Glucose:Week 56, n=1,1,1,0	-6.060 (NA)	4.420 (NA)	5.660 (NA)
Glucose:Week 60, n=1,1,1,0	2.020 (NA)	-15.930 (NA)	-1.890 (NA)
Glucose:Week 64, n=1,1,1,0	-3.030 (NA)	15.040 (NA)	-2.830 (NA)
Glucose:Week 68, n=1,0,1,0	10.100 (NA)	-0.940 (NA)
Glucose:Week 72, n=0,0,1,0	0.000 (NA)
Glucose:Week 76, n=0,0,1,0	9.430 (NA)
Glucose:Week 80, n=0,0,1,0	-2.830 (NA)
Glucose:Week 84, n=0,0,1,0	-2.830 (NA)
Glucose:Week 88, n=0,0,1,0	0.000 (NA)
Lactate dehydrogenase:Week 8, n=3,8,3,0	16.287 (3.9830)	46.694 (62.1149)	21.137 (14.3265)
Lactate dehydrogenase:Week 12, n=2,8,4,0	12.870 (3.0123)	39.709 (54.5987)	31.353 (17.3375)
Lactate dehydrogenase:Week 16, n=2,6,3,1	14.965 (10.5571)	53.818 (83.5554)	37.677 (22.5797)	36.870 (NA)
Lactate dehydrogenase:Week 20, n=2,5,3,1	13.145 (7.9832)	7.232 (21.7161)	35.440 (24.8959)	14.290 (NA)
Lactate dehydrogenase:Week 24, n=2,4,2,1	13.415 (5.7064)	81.540 (74.2387)	22.745 (2.9486)	20.280 (NA)
Lactate dehydrogenase:Week 28, n=2,3,1,1	10.485 (5.0982)	24.857 (27.3567)	26.850 (NA)	18.890 (NA)
Lactate dehydrogenase:Week 32, n=2,3,1,1	14.000 (16.2635)	63.040 (60.6775)	13.150 (NA)	33.180 (NA)
Lactate dehydrogenase:Week 36, n=2,1,0,1	20.795 (16.1432)	38.670 (NA)	12.440 (NA)
Lactate dehydrogenase:Week 40, n=0,2,0,1	75.840 (84.5983)	11.980 (NA)
Lactate dehydrogenase:Week 44, n=0,2,0,0	31.175 (79.3586)
Lactate dehydrogenase:Week 48, n=0,1,0,0	80.800 (NA)
Lactate dehydrogenase:Week 52, n=0,1,0,0	-42.640 (NA)
Lactate dehydrogenase:Week 56, n=0,1,0,0	-44.390 (NA)
Lactate dehydrogenase:Week 60, n=0,1,0,0	-41.900 (NA)
Lactate dehydrogenase:Week 64, n=0,1,0,0	-49.130 (NA)
Magnesium:Week 1, n=0,0,3,0	-2.013 (10.2561)
Magnesium:Week 2, n=9,10,11,2	3.687 (10.9267)	4.413 (5.0742)	3.593 (13.9856)	-3.205 (10.3591)
Magnesium:Week 3, n=8,11,11,2	-1.633 (4.7088)	6.602 (10.8819)	-1.808 (12.3971)	-24.200 (32.7673)
Magnesium:Week 4, n=8,11,10,2	4.104 (5.7486)	4.971 (7.7656)	1.254 (8.2818)	-20.430 (15.7685)
Magnesium:Week 5, n=10,11,9,1	-1.521 (6.3803)	5.014 (12.0008)	5.071 (8.7326)	-7.220 (NA)
Magnesium:Week 8, n=8,10,9,0	-0.370 (5.3051)	3.458 (6.0669)	3.469 (7.9381)
Magnesium:Week 12, n=7,10,7,1	0.904 (3.4827)	1.288 (10.5039)	-1.844 (7.2017)	-3.090 (NA)
Magnesium:Week 16, n=8,8,4,1	4.311 (5.1089)	0.045 (10.0780)	-3.303 (9.9862)	0.000 (NA)
Magnesium:Week 20, n=5,6,4,1	-2.720 (6.2671)	3.043 (6.1070)	-5.430 (4.0591)	-2.060 (NA)
Magnesium:Week 24, n=5,5,3,1	-1.790 (6.7929)	1.390 (11.0108)	-5.453 (1.6991)	-5.150 (NA)
Magnesium:Week 28, n=5,3,3,1	-0.512 (3.6523)	9.137 (12.3852)	-5.433 (7.6708)	-9.280 (NA)
Magnesium:Week 32, n=4,3,3,1	-0.303 (3.0947)	9.400 (15.8067)	-2.843 (4.5798)	1.030 (NA)
Magnesium:Week 36, n=3,1,3,1	-2.917 (5.0518)	13.330 (NA)	1.673 (3.8829)	-3.090 (NA)
Magnesium:Week 40, n=1,1,2,1	10.000 (NA)	13.330 (NA)	-2.780 (3.9315)	-3.090 (NA)
Magnesium:Week 44, n=1,2,2,0	-5.000 (NA)	2.315 (15.5776)	0.000 (0.0000)
Magnesium:Week 48, n=1,1,1,0	0.000 (NA)	-4.350 (NA)	-13.040 (NA)
Magnesium:Week 52, n=1,1,1,0	0.000 (NA)	-8.700 (NA)	-13.040 (NA)
Magnesium:Week 56, n=1,1,1,0	-5.000 (NA)	-8.700 (NA)	8.700 (NA)
Magnesium:Week 60, n=1,1,1,0	-5.000 (NA)	4.350 (NA)	-4.350 (NA)
Magnesium:Week 64, n=1,1,1,0	5.000 (NA)	-4.350 (NA)	-4.350 (NA)
Magnesium:Week 68, n=1,0,1,0	0.000 (NA)	0.000 (NA)
Magnesium:Week 72, n=0,0,1,0	-4.350 (NA)
Magnesium:Week 76, n=0,0,1,0	-8.700 (NA)
Magnesium:Week 80, n=0,0,1,0	-4.350 (NA)
Magnesium:Week 84, n=0,0,1,0	-4.350 (NA)
Magnesium:Week 88, n=0,0,1,0	-17.390 (NA)
Potassium:Week 1, n=0,0,3,1	2.560 (4.7011)	10.870 (NA)
Potassium:Week 2, n=11,11,12,2	6.295 (11.2391)	0.394 (10.9402)	-2.844 (9.6594)	-1.085 (13.8381)
Potassium:Week 3, n=10,11,12,2	4.095 (9.1369)	-0.879 (5.4861)	0.837 (7.9003)	-10.870 (6.1518)
Potassium:Week 4, n=10,11,11,2	5.295 (12.9147)	2.234 (10.6975)	-2.279 (8.2128)	-1.085 (1.5344)
Potassium:Week 5, n=10,11,10,1	0.613 (13.4203)	3.677 (8.4593)	0.479 (6.7468)	-4.350 (NA)
Potassium:Week 8, n=9,10,10,1	3.551 (10.1989)	-0.714 (10.4143)	-2.574 (8.8434)	0.000 (NA)
Potassium:Week 12, n=6,10,7,1	6.910 (7.7994)	0.801 (9.1329)	0.097 (6.5124)	-4.350 (NA)
Potassium:Week 16, n=8,8,4,1	3.099 (11.1450)	0.391 (7.4310)	0.825 (7.0552)	4.350 (NA)
Potassium:Week 20, n=5,6,4,1	7.054 (6.5355)	-1.055 (8.0880)	3.608 (7.3186)	-2.170 (NA)
Potassium:Week 24, n=5,5,3,1	4.250 (15.2421)	-2.684 (11.5575)	2.383 (2.4420)	-4.350 (NA)
Potassium:Week 28, n=5,4,3,1	4.134 (13.7038)	-1.040 (11.5877)	1.793 (7.5585)	-4.350 (NA)
Potassium:Week 32, n=4,3,3,1	10.555 (11.6304)	2.973 (14.6875)	-3.143 (2.7272)	4.350 (NA)
Potassium:Week 36, n=3,1,3,1	5.650 (12.0712)	18.920 (NA)	3.253 (5.6349)	-6.520 (NA)
Potassium:Week 40, n=1,2,2,1	17.070 (NA)	0.265 (7.2761)	-2.440 (3.4507)	-8.700 (NA)
Potassium:Week 44, n=1,2,2,0	12.200 (NA)	10.550 (8.0186)	5.935 (1.9587)
Potassium:Week 48, n=1,1,1,0	24.390 (NA)	-4.880 (NA)	0.000 (NA)
Potassium:Week 52, n=1,1,1,0	24.390 (NA)	-2.440 (NA)	0.000 (NA)
Potassium:Week 56, n=1,1,1,0	-2.440 (NA)	0.000 (NA)	-2.270 (NA)
Potassium:Week 60, n=1,1,1,0	12.200 (NA)	-2.440 (NA)	-4.550 (NA)
Potassium:Week 64, n=1,1,1,0	24.390 (NA)	-12.200 (NA)	-4.550 (NA)
Potassium:Week 68, n=1,0,1,0	29.270 (NA)	2.270 (NA)
Potassium:Week 72, n=0,0,1,0	-2.270 (NA)
Potassium:Week 76, n=0,0,1,0	-4.550 (NA)
Potassium:Week 80, n=0,0,1,0	4.550 (NA)
Potassium:Week 84, n=0,0,1,0	-2.270 (NA)
Potassium:Week 88, n=0,0,1,0	-6.820 (NA)
Sodium:Week 1, n=0,0,3,1	-1.657 (2.2823)	2.860 (NA)
Sodium:Week 2, n=11,11,12,2	0.013 (1.8096)	-0.370 (1.9173)	0.266 (1.7336)	0.000 (2.0223)
Sodium:Week 3, n=10,11,12,2	0.311 (1.8340)	0.009 (1.5263)	0.308 (1.6247)	1.430 (2.0223)
Sodium:Week 4, n=10,11,11,2	0.383 (1.4528)	-0.178 (1.9638)	0.545 (1.5916)	0.710 (0.0000)
Sodium:Week 5, n=10,11,10,1	0.890 (1.2598)	-0.255 (1.2916)	-0.791 (1.5272)	0.000 (NA)
Sodium:Week 8, n=9,10,10,1	0.312 (1.9462)	-0.132 (1.5679)	-0.643 (1.5180)	0.000 (NA)
Sodium:Week 12, n=6,10,7,1	0.597 (1.2596)	0.080 (1.3734)	-0.816 (1.0457)	2.140 (NA)
Sodium:Week 16, n=8,8,4,1	0.643 (1.4831)	0.009 (1.3395)	-1.773 (2.7477)	2.140 (NA)
Sodium:Week 20, n=5,6,4,1	1.904 (1.3431)	0.722 (0.6509)	-0.173 (1.2213)	-0.710 (NA)
Sodium:Week 24, n=5,5,3,1	0.584 (1.4250)	-0.424 (1.5620)	-0.953 (0.4215)	0.000 (NA)
Sodium:Week 28, n=5,4,3,1	1.606 (0.9562)	-0.538 (0.3584)	-0.237 (1.4852)	-0.710 (NA)
Sodium:Week 32, n=4,3,3,1	0.363 (0.9515)	0.953 (1.8133)	-0.233 (1.4932)	-0.710 (NA)
Sodium:Week 36, n=3,1,3,1	0.737 (1.4550)	0.000 (NA)	-0.237 (0.4099)	2.140 (NA)
Sodium:Week 40, n=1,2,2,1	2.960 (NA)	-1.385 (5.0134)	-1.070 (1.5132)	1.430 (NA)
Sodium:Week 44, n=1,2,2,0	2.220 (NA)	0.350 (0.4950)	0.725 (2.0294)
Sodium:Week 48, n=1,1,1,0	2.220 (NA)	4.320 (NA)	-1.440 (NA)
Sodium:Week 52, n=1,1,1,0	2.220 (NA)	0.720 (NA)	0.000 (NA)
Sodium:Week 56, n=1,1,1,0	3.700 (NA)	-1.440 (NA)	0.000 (NA)
Sodium:Week 60, n=1,1,1,0	2.220 (NA)	0.000 (NA)	0.000 (NA)
Sodium:Week 64, n=1,1,1,0	2.220 (NA)	0.720 (NA)	-2.160 (NA)
Sodium:Week 68, n=1,0,1,0	3.700 (NA)	0.000 (NA)
Sodium:Week 72, n=0,0,1,0	-0.720 (NA)
Sodium:Week 76, n=0,0,1,0	0.720 (NA)
Sodium:Week 80, n=0,0,1,0	0.720 (NA)
Sodium:Week 84, n=0,0,1,0	-0.720 (NA)
Sodium:Week 88, n=0,0,1,0	-0.720 (NA)
Total bilirubin:Week 1, n=0,0,3,1	-42.590 (8.4876)	-50.000 (NA)
Total bilirubin:Week 2, n=11,11,12,2	-14.740 (19.0474)	-12.683 (35.0603)	-0.972 (48.2811)	-47.220 (3.9315)
Total bilirubin:Week 3, n=10,11,12,2	-14.679 (18.3507)	-1.768 (31.6024)	-10.532 (29.0132)	-6.945 (25.5336)
Total bilirubin:Week 4, n=10,11,11,2	-2.488 (26.5820)	24.492 (57.3828)	2.855 (25.9280)	12.500 (17.6777)
Total bilirubin:Week 5, n=10,11,10,1	-0.500 (19.7836)	12.879 (40.0010)	13.944 (48.2067)	-22.220 (NA)
Total bilirubin:Week 8, n=9,10,10,1	-3.744 (22.8000)	45.680 (62.1644)	21.972 (40.2576)	-55.560 (NA)
Total bilirubin:Week 12, n=7,10,7,1	-6.276 (27.3764)	20.223 (39.6273)	4.364 (18.2751)	-44.440 (NA)
Total bilirubin:Week 16, n=8,8,4,1	-5.739 (13.8572)	16.473 (48.6051)	-4.165 (20.9713)	-44.440 (NA)
Total bilirubin:Week 20, n=5,6,4,1	4.454 (23.8194)	-15.500 (23.5242)	-15.973 (11.1972)	-22.220 (NA)
Total bilirubin:Week 24, n=5,5,3,1	-14.500 (8.7321)	-0.714 (56.6292)	-19.443 (17.3459)	-11.110 (NA)
Total bilirubin:Week 28, n=5,4,3,1	-3.182 (22.6771)	-4.165 (20.9713)	0.000 (0.0000)	-22.220 (NA)
Total bilirubin:Week 32, n=4,3,3,1	-12.215 (23.6747)	-13.890 (12.7297)	1.853 (13.9824)	-33.330 (NA)
Total bilirubin:Week 36, n=3,1,3,1	9.167 (18.7639)	50.000 (NA)	-12.963 (11.5645)	-44.440 (NA)
Total bilirubin:Week 40, n=1,2,2,1	-37.500 (NA)	-16.665 (23.5679)	-25.000 (35.3553)	-55.560 (NA)
Total bilirubin:Week 44, n=1,2,2,0	-25.000 (NA)	8.335 (58.9232)	-18.055 (9.8217)
Total bilirubin:Week 48, n=1,1,1,0	-25.000 (NA)	-16.670 (NA)	-50.000 (NA)
Total bilirubin:Week 52, n=1,1,1,0	-12.500 (NA)	-50.000 (NA)	-50.000 (NA)
Total bilirubin:Week 56, n=1,1,1,0	-50.000 (NA)	-33.330 (NA)	-25.000 (NA)
Total bilirubin:Week 60, n=1,1,1,0	-37.500 (NA)	-66.670 (NA)	-25.000 (NA)
Total bilirubin:Week 64, n=1,1,1,0	-37.500 (NA)	-66.670 (NA)	-50.000 (NA)
Total bilirubin:Week 68, n=1,0,1,0	-25.000 (NA)	-50.000 (NA)
Total bilirubin:Week 72, n=0,0,1,0	-25.000 (NA)
Total bilirubin:Week 76, n=0,0,1,0	-25.000 (NA)
Total bilirubin:Week 80, n=0,0,1,0	0.000 (NA)
Total bilirubin:Week 84, n=0,0,1,0	0.000 (NA)
Total bilirubin:Week 88, n=0,0,1,0	50.000 (NA)
Total protein:Week 1, n=0,0,3,1	1.380 (2.8026)	3.170 (NA)
Total protein:Week 2, n=11,11,12,1	2.140 (7.3161)	-14.885 (32.7433)	82.059 (278.6333)	-1.590 (NA)
Total protein:Week 3, n=10,11,12,2	-2.260 (5.4555)	-5.132 (18.9226)	60.186 (206.7731)	-0.110 (2.0930)
Total protein:Week 4, n=10,10,11,2	-0.132 (4.5645)	-5.886 (18.8830)	-0.086 (4.6004)	-9.090 (5.1053)
Total protein:Week 5, n=9,11,10,0	-8.962 (26.1684)	-5.207 (16.4970)	1.943 (6.8329)
Total protein:Week 8, n=8,10,10,0	0.981 (3.3039)	-7.914 (16.5027)	2.247 (6.1649)
Total protein:Week 12, n=7,10,7,1	0.570 (5.5899)	-7.764 (17.4075)	1.009 (4.6858)	-2.740 (NA)
Total protein:Week 16, n=8,8,4,1	0.336 (6.3130)	-10.768 (17.9309)	-4.268 (6.0907)	5.480 (NA)
Total protein:Week 20, n=5,6,3,1	-1.520 (7.6530)	-2.397 (4.8249)	2.390 (3.3674)	4.110 (NA)
Total protein:Week 24, n=5,5,3,1	-0.368 (6.3631)	-1.748 (6.0092)	-3.713 (7.2790)	2.740 (NA)
Total protein:Week 28, n=5,4,3,1	0.168 (5.4900)	-3.243 (3.2436)	0.000 (6.2070)	4.110 (NA)
Total protein:Week 32, n=4,3,3,1	0.490 (6.4817)	-4.220 (1.4543)	-1.160 (12.5647)	2.740 (NA)
Total protein:Week 36, n=2,1,3,1	-0.580 (2.9981)	-3.170 (NA)	0.447 (4.3016)	4.110 (NA)
Total protein:Week 40, n=1,2,2,1	-4.050 (NA)	-7.935 (11.2218)	-7.115 (8.1247)	-2.740 (NA)
Total protein:Week 44, n=1,2,2,0	-1.350 (NA)	-6.380 (2.2062)	-0.205 (13.8522)
Total protein:Week 48, n=1,1,1,0	-5.410 (NA)	-1.200 (NA)	-11.430 (NA)
Total protein:Week 52, n=1,1,1,0	-2.700 (NA)	-6.020 (NA)	-8.570 (NA)
Total protein:Week 56, n=1,1,1,0	-6.760 (NA)	-9.640 (NA)	-10.000 (NA)
Total protein:Week 60, n=1,1,1,0	-2.700 (NA)	-6.020 (NA)	-8.570 (NA)
Total protein:Week 64, n=1,1,1,0	-6.760 (NA)	-9.640 (NA)	-8.570 (NA)
Total protein:Week 68, n=1,0,1,0	-5.410 (NA)	-11.430 (NA)
Total protein:Week 72, n=0,0,1,0	-10.000 (NA)
Total protein:Week 76, n=0,0,1,0	-17.140 (NA)
Total protein:Week 80, n=0,0,1,0	-8.570 (NA)
Total protein:Week 84, n=0,0,1,0	-5.710 (NA)
Total protein:Week 88, n=0,0,1,0	-11.430 (NA)

7. Primary Outcome

Title	Percent Change From Baseline in Chemistry Parameters During Combination Treatment Period: Blood Urea Nitrogen (BUN), Uric Acid
Description	Blood samples were collected to analyze the chemistry parameters: BUN and uric acid. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Time Frame	Baseline (Day 1), Weeks 1, 2,3,4,5,8,12,16,20,24,28,32,36,40,44,48,52,56,60,64,68,72,76,80,84 and 88

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	10	11	12	2
BUN:Week 1, n=0,0,3,1	-10.227 (9.3008)	18.180 (NA)
BUN:Week 2, n=10,11,12,1	-5.741 (24.5046)	-7.622 (18.4784)	1.848 (44.3336)	236.360 (NA)
BUN:Week 3, n=8,11,12,1	-10.699 (18.9576)	-12.921 (8.9324)	-9.143 (22.4881)	45.450 (NA)
BUN:Week 4, n=9,11,11,1	-12.330 (16.4809)	-13.030 (17.8055)	-11.637 (19.2345)	0.000 (NA)
BUN:Week 5, n=9,11,10,0	-14.012 (12.6452)	-8.568 (18.3100)	1.857 (19.8509)
BUN:Week 8, n=9,10,10,0	-8.916 (22.6106)	-16.238 (16.8508)	-12.537 (14.8918)
BUN:Week 12, n=6,10,7,0	0.090 (20.4882)	-12.186 (20.8205)	-10.536 (18.6180)
BUN:Week 16, n=8,8,4,0	-5.259 (14.6735)	-18.011 (12.0206)	-5.560 (22.5383)
BUN:Week 20, n=5,6,4,0	-9.110 (12.9929)	-6.380 (21.2869)	-6.910 (20.6469)
BUN:Week 24, n=5,5,3,0	-4.036 (9.0958)	-13.412 (29.3172)	7.450 (8.7505)
BUN:Week 28, n=5,4,3,0	-11.508 (10.1606)	-21.773 (9.5686)	12.603 (15.4411)
BUN:Week 32, n=4,3,3,0	-8.163 (11.5276)	-7.553 (30.6672)	-16.567 (12.1882)
BUN:Week 36, n=3,1,3,0	-7.593 (12.0178)	0.000 (NA)	1.970 (29.1203)
BUN:Week 40, n=1,2,2,0	16.670 (NA)	27.885 (90.2056)	-7.275 (3.8537)
BUN:Week 44, n=1,2,2,0	-5.560 (NA)	-26.285 (13.5977)	-6.060 (15.0048)
BUN:Week 48, n=1,1,1,0	0.000 (NA)	-17.950 (NA)	-10.000 (NA)
BUN:Week 52, n=1,1,1,0	5.560 (NA)	-23.080 (NA)	-3.330 (NA)
BUN:Week 56, n=1,1,1,0	-22.220 (NA)	-30.770 (NA)	0.000 (NA)
BUN:Week 60, n=1,1,1,0	55.560 (NA)	-7.690 (NA)	-23.330 (NA)
BUN:Week 64, n=1,1,1,0	5.560 (NA)	-15.380 (NA)	-16.670 (NA)
BUN:Week 68, n=1,0,1,0	-11.110 (NA)	-26.670 (NA)
BUN:Week 72, n=0,0,1,0	-23.330 (NA)
BUN:Week 76, n=0,0,1,0	-20.000 (NA)
BUN:Week 80, n=0,0,1,0	-26.670 (NA)
BUN:Week 84, n=0,0,1,0	-10.000 (NA)
BUN:Week 88, n=0,0,1,0	-70.000 (NA)
Uric acid:Week 1, n=0,0,3,0	6.513 (3.2031)
Uric acid:Week 2, n=8,10,11,2	-11.656 (33.0629)	158.135 (499.1483)	13.357 (26.0799)	71.090 (46.6549)
Uric acid:Week 3, n=7,9,11,2	-4.581 (14.8856)	154.651 (480.5708)	0.284 (14.9816)	25.170 (38.4808)
Uric acid:Week 4, n=7,11,10,1	1.053 (12.8059)	-3.509 (7.9426)	4.436 (22.8767)	14.290 (NA)
Uric acid:Week 5, n=9,11,9,0	1.676 (8.0283)	139.415 (481.0482)	0.532 (10.9365)
Uric acid:Week 8, n=8,10,9,0	3.543 (16.5957)	-7.224 (9.7223)	0.440 (10.9092)
Uric acid:Week 12, n=6,10,6,1	4.578 (19.8500)	-1.403 (5.7519)	-0.210 (12.5985)	28.570 (NA)
Uric acid:Week 16, n=8,8,4,1	3.146 (8.8330)	-7.384 (8.5001)	-3.473 (5.4805)	52.380 (NA)
Uric acid:Week 20, n=5,5,4,1	2.232 (5.4135)	-1.796 (8.1659)	1.920 (10.9245)	38.100 (NA)
Uric acid:Week 24, n=5,5,3,1	2.570 (10.5697)	-14.008 (11.1139)	-2.893 (5.4966)	19.050 (NA)
Uric acid:Week 28, n=5,2,3,1	2.062 (14.6021)	-6.000 (8.4853)	-6.387 (5.5830)	33.330 (NA)
Uric acid:Week 32, n=4,3,3,1	8.103 (17.4601)	0.243 (27.6106)	-3.767 (9.2418)	14.290 (NA)
Uric acid:Week 36, n=3,1,3,1	0.723 (13.2198)	42.000 (NA)	-2.957 (6.4150)	9.520 (NA)
Uric acid:Week 40, n=1,2,2,1	3.030 (NA)	3.970 (36.8120)	-9.580 (1.0748)	28.570 (NA)
Uric acid:Week 44, n=1,1,2,0	-12.120 (NA)	6.000 (NA)	-1.695 (12.1552)
Uric acid:Week 48, n=1,0,1,0	-6.060 (NA)	-20.590 (NA)
Uric acid:Week 52, n=1,0,1,0	6.060 (NA)	-13.240 (NA)
Uric acid:Week 56, n=1,0,1,0	-6.060 (NA)	-4.410 (NA)
Uric acid:Week 60, n=1,0,1,0	9.090 (NA)	-1.470 (NA)
Uric acid:Week 64, n=1,0,1,0	-12.120 (NA)	-11.760 (NA)
Uric acid:Week 68, n=1,0,1,0	-6.060 (NA)	-10.290 (NA)
Uric acid:Week 72, n=0,0,1,0	-11.760 (NA)
Uric acid:Week 76, n=0,0,1,0	-20.590 (NA)
Uric acid:Week 80, n=0,0,1,0	-14.710 (NA)
Uric acid:Week 84, n=0,0,1,0	-7.350 (NA)
Uric acid:Week 88, n=0,0,1,0	-17.650 (NA)

8. Primary Outcome

Title	Percent Change From Baseline in Urine Concentration of Calcium, Creatinine Concentration, Magnesium, Phosphate, Protein During Combination Treatment Period
Description	Urine samples were collected to analyze the urinalysis parameters: Calcium, Creatinine concentration (conc), Magnesium, Phosphate and Protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).
Time Frame	Baseline (Day 1), Weeks 1, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 48, 56 and 64

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	9	7	6	2
Urine Calcium, Week 1, n=0,0,3,0	-65.187 (18.5760)
Urine Calcium, Week 3, n=8,4,5,1	-17.766 (84.7647)	-46.473 (32.8568)	-54.754 (23.2351)	-95.740 (NA)
Urine calcium, Week 4, n=6,7,6,2	1.833 (85.3207)	-43.770 (21.3110)	-38.720 (37.1828)	-87.880 (9.6167)
Urine calcium, Week 8, n=7,6,5,0	-22.406 (106.2823)	-39.052 (24.6041)	-38.834 (33.0068)
Urine calcium, Week 16, n=7,6,3,1	-15.649 (92.8636)	-41.387 (16.7494)	-39.437 (47.6551)	-54.050 (NA)
Urine calcium, Week 24, n=5,4,1,1	-18.746 (63.7505)	-35.570 (56.9229)	-80.850 (NA)	32.430 (NA)
Urine calcium, Week 32, n=4,1,1,1	-21.723 (80.8076)	-28.700 (NA)	-57.450 (NA)	-70.270 (NA)
Urine calcium, Week 40, n=1,1,1,1	7.690 (NA)	-69.500 (NA)	3.570 (NA)	0.000 (NA)
Urine calcium, Week 48, n=1,1,0,0	63.080 (NA)	-69.570 (NA)
Urine calcium, Week 56, n=1,1,0,0	149.230 (NA)	-42.030 (NA)
Urine calcium, Week 64, n=1,0,0,0	13.850 (NA)
Urine Creatinine conc, Week 4, n=3,2,2,0	-4.953 (32.2945)	-2.095 (44.4699)	-28.210 (26.3609)
Urine Creatinine conc, Week 8, n=4,2,2,0	-6.328 (17.8300)	-6.815 (21.1071)	-28.420 (14.5947)
Urine Creatinine conc, Week 12, n=2,2,2,0	23.965 (75.8372)	55.315 (124.3447)	-68.290 (30.3207)
Urine Creatinine conc, Week 16, n=1,2,1,0	87.930 (NA)	-38.040 (15.3725)	-38.920 (NA)
Urine Creatinine conc, Week 20, n=3,2,1,0	34.260 (62.0584)	-56.830 (14.2694)	-56.760 (NA)
Urine Creatinine conc, Week 24, n=2,1,0,0	14.140 (43.4022)	-15.730 (NA)
Urine Creatinine conc, Week 28, n=3,0,0,0	-39.680 (53.3702)
Urine Creatinine conc, Week 32, n=2,0,0,0	45.985 (16.6524)
Urine Creatinine conc, Week 36, n=1,0,1,1	28.450 (NA)	11.350 (NA)	-23.400 (NA)
Urine Creatinine conc, Week 40, n=0,0,1,1	-67.570 (NA)	-16.490 (NA)
Urine Magnesium, Week 3, n=5,3,3,0	-3.814 (33.8771)	-22.173 (21.2675)	-25.617 (41.4271)
Urine Magnesium, Week 4, n=5,4,3,0	-18.914 (34.9200)	48.198 (36.5733)	-38.777 (21.3399)
Urine Magnesium, Week 8, n=4,4,3,0	0.080 (97.5606)	22.425 (45.1613)	-46.677 (18.8832)
Urine Magnesium, Week 16, n=2,3,0,0	33.510 (124.1680)	4.530 (17.5296)
Urine Magnesium, Week 24, n=3,2,0,0	-13.997 (66.1097)	8.425 (50.4804)
Urine Magnesium, Week 32, n=3,1,0,0	4.147 (77.8921)	82.350 (NA)
Urine Magnesium, Week 40, n=1,0,0,0	-77.050 (NA)
Urine Magnesium, Week 48, n=1,0,0,0	47.540 (NA)
Urine Magnesium, Week 56, n=1,0,0,0	-13.110 (NA)
Urine Magnesium, Week 64, n=1,0,0,0	19.670 (NA)
Urine Phosphate, Week 1, n=0,0,2,0	7.800 (18.9646)
Urine Phosphate, Week 3, n=8,4,5,0	9.118 (45.4234)	41.553 (63.8281)	12.918 (59.9265)
Urine Phosphate, Week 4, n=9,6,5,1	1.980 (50.5354)	55.768 (99.4820)	-13.832 (24.3081)	-57.640 (NA)
Urine Phosphate, Week 8, n=7,7,4,0	30.650 (76.2619)	61.757 (109.4144)	-0.638 (28.7487)
Urine Phosphate, Week 16, n=6,5,2,1	23.998 (77.8683)	60.884 (85.7357)	52.270 (74.6422)	29.060 (NA)
Urine Phosphate, Week 24, n=5,3,1,1	84.308 (119.7584)	25.007 (76.8139)	-23.470 (NA)	-0.990 (NA)
Urine Phosphate, Week 32, n=4,2,1,1	48.388 (121.3648)	-22.530 (15.2735)	-2.040 (NA)	-65.020 (NA)
Urine Phosphate, Week 40, n=1,1,1,1	0.000 (NA)	-39.080 (NA)	-3.030 (NA)	-12.320 (NA)
Urine Phosphate, Week 48, n=1,0,0,0	222.220 (NA)
Urine Phosphate, Week 56, n=1,0,0,0	-48.150 (NA)
Urine Phosphate, Week 64, n=1,0,0,0	37.040 (NA)
Urine Protein, Week 4, n=0,1,0,0	-13.790 (NA)
Urine Protein, Week 12, n=0,0,1,0	-53.850 (NA)
Urine Protein, Week 16, n=0,1,1,0	-6.900 (NA)	-30.770 (NA)
Urine Protein, Week 20, n=0,0,1,0	-53.850 (NA)
Urine Protein, Week 24, n=0,1,0,0	-12.640 (NA)
Urine Protein, Week 28, n=1,0,0,0	-99.430 (NA)
Urine Protein, Week 32, n=1,0,0,0	-34.780 (NA)
Urine Protein, Week 36, n=0,0,1,1	38.460 (NA)	33.330 (NA)
Urine Protein, Week 40, n=0,0,1,1	-53.850 (NA)	25.000 (NA)

9. Primary Outcome

Title	Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings During Combination Treatment Period
Description	A 12-lead ECG was obtained after the participant had rested at least 5 minutes in a semi-recumbent or supine position at each time point during the study using ECG machine that automatically measured PR, QRS, QT and Corrected QT interval (QT duration corrected for heart rate by Bazett's formula [QTcB] and Fridericia's formula [QTcF]). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal clinical significant ECG findings are presented.
Time Frame	Weeks 4, 8, 16, 24, 32, 40, 48, 56, 64, 72, 80 and 88

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	10	9	11	1
Week 4, n=10,8,11,1	0 0%	0 NaN	0 NaN	0 NaN
Week 8, n=8,9,8,0	0 0%	1 NaN	1 NaN
Week 16, n=8,8,3,1	0 0%	0 NaN	0 NaN	0 NaN
Week 24, n=5,5,3,1	0 0%	0 NaN	0 NaN	0 NaN
Week 32, n=4,3,3,1	0 0%	0 NaN	1 NaN	0 NaN
Week 40, n=1,0,2,1	0 0%	0 NaN	0 NaN
Week 48, n=1,1,1,0	0 0%	0 NaN	0 NaN
Week 56, n=1,0,1,0	0 0%	0 NaN
Week 64, n=1,0,1,0	0 0%	0 NaN
Week 72, n=0,0,1,0	0 0%
Week 80, n=0,0,1,0	0 0%
Week 88, n=0,0,1,0	0 0%

10. Primary Outcome

Title	Number of Participants With Worst Case Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Results by Maximum Grade Increase Post-Baseline Relative to Baseline During Combination Treatment Period
Description	SBP and DBP were measured after resting for 5 minutes in semi-supine position. SBP and DBP were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. 'Any grade increase' is defined as an increase in CTCAE grade relative to Baseline grade. For SBP, Grade 0: <120 millimeters of mercury [mmHg]), Grade 1: 120-139 mmHg, Grade 2: 140-159 mmHg, Grade 3:>=160 mmHg. For DBP, Grade 0: <80 mmHg, Grade 1: 80-89 mmHg, Grade 2: 90-99 mmHg, Grade 3: >=100 mmHg. Higher grade indicate worst outcome. Data for worst-case post-Baseline is reported.
Time Frame	Up to maximum 654 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	2
SBP, Any Grade Increase	8 21.6%	6 NaN	5 NaN	1 NaN
SBP, Increase to Grade 2	3 8.1%	1 NaN	3 NaN	0 NaN
SBP, Increase to Grade 3	3 8.1%	2 NaN	1 NaN	0 NaN
DBP, Any Grade Increase	8 21.6%	6 NaN	5 NaN	2 NaN
DBP, Increase to Grade 2	6 16.2%	4 NaN	2 NaN	1 NaN
DBP, Increase to Grade 3	0 0%	0 NaN	0 NaN	0 NaN

11. Primary Outcome

Title	Number of Participants With Worst Case Post-Baseline Results for Heart Rate During Combination Treatment Period
Description	Heart rate was measured after resting for 5 minutes in semi-supine position. The clinical concern range for heart rate was: low: decrease to <60 beats per minute (bpm) and high: increase to >100 bpm. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decrease to <60 bpm' and 'increase to >100 bpm' during post-Baseline visits. Data for worst case post-Baseline is reported.
Time Frame	Up to maximum 654 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	2
Decrease to <60	2 5.4%	2 NaN	6 NaN	1 NaN
Change to normal or no change	8 21.6%	7 NaN	5 NaN	1 NaN
Increase to >100	1 2.7%	3 NaN	1 NaN	1 NaN

12. Primary Outcome

Title	Number of Participants With Worst Case Post-Baseline Results for Body Temperature During Combination Treatment Period
Description	Temperature was measured after resting for 5 minutes in semi-supine position. The clinical concern range for body temperature was: low: decrease to <=35 degrees celsius, high: increase to >=38 degrees celsius. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decreased to <=35 degree celsius' and 'increased to >=38 degrees celsius' during post-Baseline visits. Data for worst-case post-Baseline is presented.
Time Frame	Up to maximum 654 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	10	12	2
Decrease to <=35	0 0%	0 NaN	0 NaN	0 NaN
Change to normal or no change	11 29.7%	10 NaN	10 NaN	2 NaN
Increase to >=38	0 0%	0 NaN	2 NaN	0 NaN

13. Primary Outcome

Title	Non-progressive Disease (Non-PD) Rate at Week 12 According to Prostate Cancer Working Group 2 (PCWG2) Criteria in GSK2636771 200mg/Enzalutamide 160mg - Overall Arm
Description	The 12-week non-PD rate was defined as percentage of participants without progression(non-PD) at Week12 as determined from Prostate-specific antigen(PSA) results, radiographic assessment per Response Evaluation Criteria In Solid Tumors(RECIST)1.1 and bone scan.Disease progression was defined by 1 or more of the following:PSA progression alone; PSA progression according to the PCWG2 criteria with accompanying progression by RECIST1.1 or bone scan for participants with soft tissue Baseline disease; Bone progression on bone scan according to PCWG2 criteria; or Radiographic progression in soft tissue or bone by RECIST1.1 for participants with Baseline disease.Modified All Treated Clinical Activity Population consisted of all participants who received at least 1 dose of GSK2636771 and who were treated at the same dose as dose expansion cohort and have been on study drug for at least 12weeks or have discontinued study treatment due to disease progression, died or withdrawn for any reason.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

Modified All Treated Clinical Activity Population. The hypothesis for 12-week non-PD rate was to be tested on a combination of data provided in the dose escalation and dose expansion phase. The 200 mg dose was the only one that had a dose expansion phase. Hence, a combined arm of GSK2636771 200 mg/ Enzalutamide 160 mg has been presented.

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg - Overall
Arm/Group Description	Participants received GSK2636771 200 mg with enzalutamide 160 mg either in dose escalation cohort or in dose expansion cohort. This arm contain combined data for dose escalation and dose expansion cohorts of GSK2636771 200 mg/ Enzalutamide 160 mg.
Measure Participants	22
Number [Percentage of participants]	50 135.1%

14. Secondary Outcome

Title	Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate at 12 Weeks During Combination Treatment Period
Description	PSA50 response rate is defined as percentage of participants with a decrease of >=50% in the PSA concentration from the Baseline PSA value determined at least 12 weeks after start of treatment until last post-treatment follow-up visit or initiation of new anti-cancer therapy and confirmed after 3 or more weeks by an additional PSA evaluation. Confirmed PSA50 is defined as decline of >=50% in PSA concentration from Baseline.
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

All treated Clinical Activity Population consisted of all participants who received at least one dose of GSK2636771.

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	2
Number [Percentage of participants]	9 24.3%	9 NaN	8 NaN	50 NaN

15. Secondary Outcome

Title	Objective Response Rate (ORR) During Combination Treatment Period
Description	ORR is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per RECIST Version (v) 1.1 criteria; where CR: Disappearance of all target lesions; PR: at least 30% decrease in the sum of the longest diameter of target lesions with reference to Baseline sum of diameters.
Time Frame	Up to maximum 654 days

Outcome Measure Data

Analysis Population Description

All Treated Clinical Activity Population

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	2
CR	0 0%	0 NaN	0 NaN	0 NaN
PR	9 24.3%	0 NaN	0 NaN	0 NaN

16. Secondary Outcome

Title	Time to PSA Progression According to PCWG2 Criteria During Combination Treatment Period
Description	Time to PSA progression is defined as the time from combination study treatment start until the first PSA progression per PCWG2 criteria (confirmed if there has been a PSA decline from Baseline). Time to PSA was analyzed using Kaplan-Meier methods. Median and inter-quartile range (first and third quartile) are presented.
Time Frame	Up to maximum 654 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	1
Median (Inter-Quartile Range) [Weeks]	19.1	14.6	11.4	11.9

17. Secondary Outcome

Title	Time to Radiological Progression According to PCWG2 Criteria During Combination Treatment Period
Description	Time to radiological progression is defined as the time from combination study treatment start until the first radiological progression by PCWG2 criteria. Time to radiological progession was analyzed using Kaplan-Meier methods. For participants who do not progress, participants were censored at the time of last radiological scan or date of death. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of GSK2636771 drug. Median and inter-quartile range (first and third quartile) are presented.
Time Frame	Up to maximum 654 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	1
Median (Inter-Quartile Range) [Weeks]	38.1	23.1	21.9	38.9

18. Secondary Outcome

Title	Radiological Progression Free Survival (rPFS) Per PCWG2 Criteria During Combination Treatment Period
Description	rPFS is defined as the interval of time (in weeks) between the date of first dose of GSK2636771 and the earlier of the date of disease progression as assessed by the investigator per RECIST version 1.1 criteria and the date of death due to any cause. For participants who do not progress or die, participants were censored at the time of last radiological scan. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of GSK2636771 drug. rPFS was analyzed using Kaplan-Meier methods. Median and inter-quartile range (first and third quartile) are presented.
Time Frame	Up to maximum 654 days

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	11	11	12	1
Median (Inter-Quartile Range) [Weeks]	38.1	23.1	21.9	38.9

19. Secondary Outcome

Title	Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2636771.
Time Frame	Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Expansion
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.
Measure Participants	7
Week 5: Pre-dose, n=6	4035.000 (2650.9602)
Week 5: 1 hour, n=6	4758.333 (1818.9823)
Week 5: 2 hours, n=7	7124.286 (4328.2362)
Week 5: 3 hours, n=7	9565.714 (4422.4648)
Week 5: 5-6 hours, n=1	14600.000 (NA)
Week 5: 6-7 hours, n=1	13400.000 (NA)
Week 5: 7-8 hours, n=1	14800.000 (NA)
Week 8: Pre-dose, n=7	6291.429 (3742.1492)
Week 12: Pre-dose, n=6	5328.333 (2756.5879)

20. Secondary Outcome

Title	Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2636771. Pharmacokinetic Concentration Population consisted of all participants in the All Treated Safety Population for whom a blood sample for pharmacokinetics were obtained, analyzed, and was measurable.
Time Frame	Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	8	8	1
Week 5: Pre-dose, n=8,8,1	6720.000 (3376.1136)	5142.500 (1613.1402)	0.000 (NA)
Week 5: 0.5 hours, n=8,6,1	8059.250 (4085.9045)	5008.333 (1170.4771)	292.000 (NA)
Week 5: 1 hours, n=7,7,1	8620.714 (4561.6832)	5794.286 (994.8175)	433.000 (NA)
Week 5: 2 hours, n=8,8,1	8811.875 (4424.590)	8408.750 (1764.7374)	3510.000 (NA)
Week 5: 3 hours, n=8, 8,1	9776.875 (4869.5519)	10510.000 (3375.0725)	6690.000 (NA)
Week 5: 4 hours, n=7,8,1	8921.429 (4857.7959)	11250.000 (3639.5172)	9060.000 (NA)
Week 5: 6 hours, n=6,8,0	7264.833 (4319.3051)	10073.750 (3000.0664)
Week 8: Pre-dose, n=7,6,0	9354.286 (3676.1477)	7333.333 (4236.7802)
Week 12: Pre-dose, n=6,5,0	7938.333 (3801.3756)	8036.000 (3025.3479)

21. Secondary Outcome

Title	Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of enzalutamide.
Time Frame	Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Concentration Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles). Blood samples were not collected for analysis of Enzalutamide for GSK2636771 400mg/Enzalutamide 160mg Escalation arm.

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	9	7	0
Week 5: Pre-dose, n=9,7,0	12.131 (3.0795)	12.134 (3.2382)
Week 5: 0.5 hours, n=9,6,0	14.178 (2.4929)	13.545 (3.9395)
Week 5: 1 hours, n=7,7,0	14.771 (2.8224)	14.829 (2.7980)
Week 5: 2 hours, n=9,7,0	13.611 (3.5674)	14.200 (2.7761)
Week 5: 3 hours, n=8,7,0	14.600 (3.4748)	12.586 (2.8416)
Week 5: 4 hours, n=9,7,0	12.536 (3.3727)	12.466 (3.4905)
Week 5: 6 hours, n=7,7,0	11.741 (3.0012)	12.150 (3.6842)
Week 8: Pre-dose, n=5,5,0	13.140 (2.7337)	12.240 (2.1126)
Week 12: Pre-dose, n=4,4,0	12.333 (3.8684)	12.750 (1.6176)

22. Secondary Outcome

Title	Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of enzalutamide.
Time Frame	Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Expansion
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.
Measure Participants	8
Week 5: Pre-dose, n=6	11.735 (2.3463)
Week 5: 1 hour, n=7	14.793 (3.8293)
Week 5: 2 hours, n=7	13.274 (2.9788)
Week 5: 3 hours, n=7	12.886 (4.1615)
Week 5: 5-6 hours, n=2	13.800 (0.7071)
Week 5: 6-7 hours, n=2	13.300 (1.4142)
Week 5: 7-8 hours, n=2	12.750 (0.3536)
Week 8: Pre-dose, n=8	11.335 (2.5525)
Week 12: Pre-dose, n=6	11.520 (3.1956)

23. Secondary Outcome

Title	Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of N-desmethyl enzalutamide.
Time Frame	Week 5: Pre-dose, 0.5, 1, 2, 3, 4, 6 hours post-dose; Weeks 8 and 12: Pre-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Concentration Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles). Blood samples were not collected for analysis of Enzalutamide for GSK2636771 400mg/Enzalutamide 160mg Escalation arm.

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.	Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
Measure Participants	9	7	0
Week 5: Pre-dose, n=9,7,0	13.057 (3.5612)	12.583 (4.4768)
Week 5: 0.5 hours, n=9,6,0	13.257 (3.0229)	12.208 (4.9689)
Week 5: 1 hours, n=7,7,0	12.736 (2.6587)	11.350 (4.4129)
Week 5: 2 hours, n=9,7,0	11.710 (2.7646)	11.449 (3.9828)
Week 5: 3 hours, n=8,7,0	13.189 (2.5728)	11.136 (4.4445)
Week 5: 4 hours, n=9,7,0	11.426 (2.1615)	10.703 (3.5853)
Week 5: 6 hours, n=7,7,0	11.256 (2.6641)	10.416 (1.7444)
Week 8: Pre-dose, n=5,5,0	14.200 (1.7450)	13.348 (4.4348)
Week 12: Pre-dose, n=4,4,0	13.665 (5.3833)	11.958 (2.4890)

24. Secondary Outcome

Title	Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of N-desmethyl enzalutamide.
Time Frame	Week 5: Pre-dose, 1, 2, 3, 5-6, 6-7, 7-8 hours post-dose; Weeks 8 and 12: Pre-dose

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK2636771 200mg/Enzalutamide 160mg Expansion
Arm/Group Description	Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.
Measure Participants	8
Week 5: Pre-dose, n=6	11.623 (3.5552)
Week 5: 1 hour, n=7	12.476 (3.6642)
Week 5: 2 hours, n=7	12.069 (3.9492)
Week 5: 3 hours, n=7	11.861 (4.1782)
Week 5: 5-6 hours, n=2	11.850 (0.3536)
Week 5: 6-7 hours, n=2	11.135 (2.7789)
Week 5: 7-8 hours, n=2	11.050 (2.8991)
Week 8: Pre-dose, n=8	14.450 (4.7827)
Week 12: Pre-dose, n=6	15.690 (7.4271)

Adverse Events

Time Frame	Up to Week 2 for run-in period and up to maximum of 675 days for combination treatment period
Adverse Event Reporting Description	All Treated Safety Population consisted of all participants who received at least one dose of GSK2636771 or Enzalutamide.
Arm/Group Title	Enzalutamide Only (run-in Period)		GSK2636771 200mg/Enzalutamide 160mg Escalation		GSK2636771 200mg/Enzalutamide 160mg Expansion		GSK2636771 300mg/Enzalutamide 160mg Escalation		GSK2636771 400mg/Enzalutamide 160mg Escalation
Arm/Group Description	Participants received enzalutamide monotherapy at the approved dose of 160 mg once daily orally for 14 days in run-in period to achieve near-steady-state levels of enzalutamide prior to initiating combination therapy with GSK2636771. Participants who completed the Enzalutamide run-in period continued with the combination therapy with GSK2636771.		Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.		Participants received GSK2636771 200 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose expansion cohort. Participants were enrolled in this cohort as an expansion of the dose escalation cohort (GSK2636771 200 mg/ enzalutamide 160 mg) to collect adequate data on safety, pharmacokinetics and pharmacodynamics.		Participants received GSK2636771 300 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.		Participants received GSK2636771 400 mg once daily orally in combination with enzalutamide 160 mg orally once daily in dose escalation cohort.
All Cause Mortality
	Enzalutamide Only (run-in Period)		GSK2636771 200mg/Enzalutamide 160mg Escalation		GSK2636771 200mg/Enzalutamide 160mg Expansion		GSK2636771 300mg/Enzalutamide 160mg Escalation		GSK2636771 400mg/Enzalutamide 160mg Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/37 (0%)		0/11 (0%)		0/11 (0%)		0/12 (0%)		0/2 (0%)
Serious Adverse Events
	Enzalutamide Only (run-in Period)		GSK2636771 200mg/Enzalutamide 160mg Escalation		GSK2636771 200mg/Enzalutamide 160mg Expansion		GSK2636771 300mg/Enzalutamide 160mg Escalation		GSK2636771 400mg/Enzalutamide 160mg Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/37 (2.7%)		2/11 (18.2%)		2/11 (18.2%)		2/12 (16.7%)		0/2 (0%)
Gastrointestinal disorders
Abdominal pain	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Gastrointestinal haemorrhage	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Infections and infestations
Cellulitis	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Injury, poisoning and procedural complications
Fall	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Metabolism and nutrition disorders
Hypocalcaemia	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Nervous system disorders
Cerebrovascular accident	1/37 (2.7%)	1	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Haematuria	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	4	0/12 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Haemoptysis	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Pleural effusion	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Enzalutamide Only (run-in Period)		GSK2636771 200mg/Enzalutamide 160mg Escalation		GSK2636771 200mg/Enzalutamide 160mg Expansion		GSK2636771 300mg/Enzalutamide 160mg Escalation		GSK2636771 400mg/Enzalutamide 160mg Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/37 (29.7%)		11/11 (100%)		11/11 (100%)		12/12 (100%)		2/2 (100%)
Blood and lymphatic system disorders
Anaemia	0/37 (0%)	0	3/11 (27.3%)	4	1/11 (9.1%)	1	5/12 (41.7%)	5	1/2 (50%)	2
Leukopenia	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	1/2 (50%)	1
Lymphopenia	1/37 (2.7%)	1	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	1/2 (50%)	1
Neutropenia	0/37 (0%)	0	2/11 (18.2%)	2	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Cardiac disorders
Palpitations	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Sinus bradycardia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Tachycardia	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Endocrine disorders
Hyperparathyroidism	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/37 (2.7%)	1	6/11 (54.5%)	10	8/11 (72.7%)	19	7/12 (58.3%)	7	2/2 (100%)	3
Nausea	0/37 (0%)	0	4/11 (36.4%)	4	1/11 (9.1%)	1	3/12 (25%)	3	0/2 (0%)	0
Constipation	0/37 (0%)	0	2/11 (18.2%)	2	1/11 (9.1%)	1	1/12 (8.3%)	1	1/2 (50%)	1
Abdominal discomfort	0/37 (0%)	0	0/11 (0%)	0	2/11 (18.2%)	2	0/12 (0%)	0	1/2 (50%)	1
Abdominal pain	0/37 (0%)	0	1/11 (9.1%)	1	1/11 (9.1%)	2	1/12 (8.3%)	1	0/2 (0%)	0
Vomiting	0/37 (0%)	0	0/11 (0%)	0	2/11 (18.2%)	2	0/12 (0%)	0	1/2 (50%)	1
Abdominal distension	0/37 (0%)	0	1/11 (9.1%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Abdominal pain upper	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	3	0/12 (0%)	0	0/2 (0%)	0
Abdominal tenderness	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Anorectal discomfort	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/2 (50%)	1
Defaecation urgency	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Dry mouth	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/2 (50%)	1
Dyspepsia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Flatulence	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	2	0/12 (0%)	0	0/2 (0%)	0
Gastrointestinal disorder	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/2 (50%)	1
Inguinal hernia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Mouth ulceration	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Toothache	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
General disorders
Fatigue	0/37 (0%)	0	3/11 (27.3%)	3	4/11 (36.4%)	5	4/12 (33.3%)	5	0/2 (0%)	0
Oedema peripheral	0/37 (0%)	0	0/11 (0%)	0	2/11 (18.2%)	2	1/12 (8.3%)	1	0/2 (0%)	0
Malaise	0/37 (0%)	0	1/11 (9.1%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Pyrexia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Chills	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Early satiety	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Face oedema	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Gait disturbance	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Pain	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Peripheral swelling	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Immune system disorders
Hypersensitivity	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Infections and infestations
Urinary tract infection	1/37 (2.7%)	1	1/11 (9.1%)	2	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Bronchitis	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Cellulitis	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Conjunctivitis	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Nasopharyngitis	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Injury, poisoning and procedural complications
Fall	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Skin laceration	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Investigations
Blood creatinine increased	0/37 (0%)	0	2/11 (18.2%)	3	1/11 (9.1%)	1	2/12 (16.7%)	3	1/2 (50%)	2
Blood alkaline phosphatase increased	0/37 (0%)	0	2/11 (18.2%)	2	3/11 (27.3%)	3	0/12 (0%)	0	0/2 (0%)	0
Blood bilirubin increased	0/37 (0%)	0	0/11 (0%)	0	2/11 (18.2%)	3	1/12 (8.3%)	1	0/2 (0%)	0
Lymphocyte count decreased	0/37 (0%)	0	1/11 (9.1%)	1	2/11 (18.2%)	2	0/12 (0%)	0	0/2 (0%)	0
Aspartate aminotransferase increased	0/37 (0%)	0	1/11 (9.1%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Blood phosphorus increased	0/37 (0%)	0	1/11 (9.1%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Weight decreased	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	0/2 (0%)	0
Alanine aminotransferase increased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Blood 25-hydroxycholecalciferol decreased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Blood lactate dehydrogenase increased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Blood parathyroid hormone increased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Eosinophil count increased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Haematocrit decreased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Haemoglobin decreased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Heart rate increased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Neutrophil count decreased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Platelet count decreased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Red blood cell count decreased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Thyroxine decreased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Urine potassium increased	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/37 (0%)	0	2/11 (18.2%)	2	4/11 (36.4%)	5	5/12 (41.7%)	5	0/2 (0%)	0
Hypocalcaemia	0/37 (0%)	0	2/11 (18.2%)	3	1/11 (9.1%)	1	5/12 (41.7%)	7	1/2 (50%)	1
Hypermagnesaemia	0/37 (0%)	0	0/11 (0%)	0	2/11 (18.2%)	2	3/12 (25%)	3	0/2 (0%)	0
Hyperkalaemia	0/37 (0%)	0	2/11 (18.2%)	2	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Hypomagnesaemia	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	1/2 (50%)	1
Hyponatraemia	0/37 (0%)	0	1/11 (9.1%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Hypophosphataemia	0/37 (0%)	0	2/11 (18.2%)	3	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Gout	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Hypercreatininaemia	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Hyperglycaemia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Hypernatraemia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Hypoalbuminaemia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Hypokalaemia	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/37 (2.7%)	1	1/11 (9.1%)	1	2/11 (18.2%)	2	1/12 (8.3%)	1	1/2 (50%)	2
Back pain	2/37 (5.4%)	2	1/11 (9.1%)	1	1/11 (9.1%)	2	3/12 (25%)	3	0/2 (0%)	0
Pain in extremity	0/37 (0%)	0	2/11 (18.2%)	2	1/11 (9.1%)	1	2/12 (16.7%)	2	0/2 (0%)	0
Musculoskeletal pain	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	2/12 (16.7%)	2	0/2 (0%)	0
Bone pain	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1	0/2 (0%)	0
Groin pain	1/37 (2.7%)	1	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	0/2 (0%)	0
Muscle spasms	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	0/2 (0%)	0
Spinal pain	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	3	0/2 (0%)	0
Arthritis	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Flank pain	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/2 (50%)	1
Muscle twitching	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Muscular weakness	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Musculoskeletal chest pain	2/37 (5.4%)	2	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Myalgia intercostal	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Nervous system disorders
Dizziness	0/37 (0%)	0	2/11 (18.2%)	2	1/11 (9.1%)	1	1/12 (8.3%)	1	0/2 (0%)	0
Dysgeusia	0/37 (0%)	0	2/11 (18.2%)	2	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Headache	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	1/2 (50%)	1
Taste disorder	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	2/12 (16.7%)	2	0/2 (0%)	0
Cauda equina syndrome	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Paraesthesia	1/37 (2.7%)	1	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Sciatica	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Syncope	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Psychiatric disorders
Confusional state	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Agitation	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Anxiety	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Depression	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Insomnia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Renal and urinary disorders
Haematuria	0/37 (0%)	0	2/11 (18.2%)	2	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Proteinuria	0/37 (0%)	0	1/11 (9.1%)	1	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Dysuria	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Hydronephrosis	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Pollakiuria	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Urinary incontinence	0/37 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0	0/2 (0%)	0
Reproductive system and breast disorders
Breast pain	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Pelvic pain	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Perineal pain	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/2 (50%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/37 (0%)	0	2/11 (18.2%)	2	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Oropharyngeal pain	0/37 (0%)	0	2/11 (18.2%)	2	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Epistaxis	1/37 (2.7%)	1	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Sinus congestion	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Dermatitis	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Dry skin	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Pain of skin	1/37 (2.7%)	1	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Pruritus	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/2 (50%)	1
Rash	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0	0/2 (0%)	0
Rash macular	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	0/12 (0%)	0	1/2 (50%)	2
Rash maculo-papular	0/37 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1	0/2 (0%)	0
Vascular disorders
Hypertension	0/37 (0%)	0	1/11 (9.1%)	1	3/11 (27.3%)	4	3/12 (25%)	3	0/2 (0%)	0
Hot flush	0/37 (0%)	0	1/11 (9.1%)	1	3/11 (27.3%)	3	0/12 (0%)	0	0/2 (0%)	0
Hypotension	0/37 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	1/12 (8.3%)	2	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.