CompletedNCT02215096Updated Oct 22, 2020Results posted

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

A Phase 1 interventional study of GSK2636771 and Enzalutamide in Neoplasms, sponsored by GlaxoSmithKline. Completed at 9 sites in 2 countries. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-10-22.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 37
Allocation: Non-randomized
Ages: 18 Years and older
Sex: Male

Study 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

Conditions studied

Neoplasms

Browse trials for

Prostatic Neoplasms 6,370

Keywords

enzalutamide
metastatic castration-resistant prostate cancer
GSK2636771
PI3K-beta
PTEN deficiency

In context

Prostatic Neoplasms

6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.

This study's enrollment of 37 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: 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

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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 37 participants (actual)

Study arms

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 · Drug: Enzalutamide
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 · Drug: Enzalutamide

Interventions

DrugGSK2636771
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
DrugEnzalutamide
Enzalutamide will be sourced locally from commercial stock for sites in countries where it is approved

What researchers measure

Primary outcomes

Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period
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
Number of Participants With Non-SAEs and SAEs During Combination Treatment Period
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
Number of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period
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
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
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
Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: International Normalized Ratio (INR), Prothrombin Time (PT), Partial Thromboplastin Time (PTT)
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
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
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
Percent Change From Baseline in Chemistry Parameters During Combination Treatment Period: Blood Urea Nitrogen (BUN), Uric Acid
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
Percent Change From Baseline in Urine Concentration of Calcium, Creatinine Concentration, Magnesium, Phosphate, Protein During Combination Treatment Period
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
Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings During Combination Treatment Period
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
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
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
Number of Participants With Worst Case Post-Baseline Results for Heart Rate During Combination Treatment Period
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
Number of Participants With Worst Case Post-Baseline Results for Body Temperature During Combination Treatment Period
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
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
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

Secondary outcomes

Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate at 12 Weeks During Combination Treatment Period
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
Objective Response Rate (ORR) During Combination Treatment Period
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
Time to PSA Progression According to PCWG2 Criteria During Combination Treatment Period
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
Time to Radiological Progression According to PCWG2 Criteria During Combination Treatment Period
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
Radiological Progression Free Survival (rPFS) Per PCWG2 Criteria During Combination Treatment Period
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
Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
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
Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
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
Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
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
Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
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
Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
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
Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
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

Results

Posted Oct 22, 2020

Participant flow

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.

Run-In Period (Up to Week 2)

Participant flow — Run-In Period (Up to Week 2)
Milestone	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
Started	37	0	0	0	0
Completed	36	0	0	0	0
Not completed	1	0	0	0	0
Withdrew: Adverse event	1	0	0	0	0

Combination TP (Up to Maximum 654 Days)

Participant flow — Combination TP (Up to Maximum 654 Days)
Milestone	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Started	11	11	12	2
Completed	9	10	10	1
Not completed	2	1	2	1
Withdrew: Physician decision	0	0	0	1
Withdrew: Lost to follow-up	0	0	1	0
Withdrew: Withdrawal by subject	2	1	1	0

Outcome measures

PrimaryNumber of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period

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
Reported as:: Count of participants · Participants

Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) During run-in Period
Participants	Enzalutamide Only (run-in Period)
Non-SAEs	11
SAEs	1

PrimaryNumber of Participants With Non-SAEs and SAEs During Combination Treatment Period

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
Reported as:: Count of participants · Participants

Number of Participants With Non-SAEs and SAEs During Combination Treatment Period
Participants	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Non-SAEs	11	11	12	2
SAEs	2	2	2	0

PrimaryNumber of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period

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
Reported as:: Count of participants · Participants

Number of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period
Participants	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Number of Participant With Dose-limiting Toxicities (DLT) During Combination Treatment Period	1	0	2	2

PrimaryPercent Change From Baseline in Hematology Parameters During Combination Treatment Period: Basophils, Eosinophils, Hematocrit, Hemoglobin, Lymphocytes, MCH, MCV, Monocytes, Total Neutrophils, Platelet Count, WBC Count

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
Reported as:: Mean · Percent change

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
Percent change	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
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	—

PrimaryPercent Change From Baseline in Hematology Parameters During Combination Treatment Period: International Normalized Ratio (INR), Prothrombin Time (PT), Partial Thromboplastin Time (PTT)

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
Reported as:: Mean · Percent change

Percent Change From Baseline in Hematology Parameters During Combination Treatment Period: International Normalized Ratio (INR), Prothrombin Time (PT), Partial Thromboplastin Time (PTT)
Percent change	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
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	—

PrimaryPercent 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

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
Reported as:: Mean · Percent change

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
Percent change	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
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	—

PrimaryPercent Change From Baseline in Chemistry Parameters During Combination Treatment Period: Blood Urea Nitrogen (BUN), Uric Acid

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
Reported as:: Mean · Percent change

Percent Change From Baseline in Chemistry Parameters During Combination Treatment Period: Blood Urea Nitrogen (BUN), Uric Acid
Percent change	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
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	—

PrimaryPercent Change From Baseline in Urine Concentration of Calcium, Creatinine Concentration, Magnesium, Phosphate, Protein During Combination Treatment Period

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
Reported as:: Mean · Percent change

Percent Change From Baseline in Urine Concentration of Calcium, Creatinine Concentration, Magnesium, Phosphate, Protein During Combination Treatment Period
Percent change	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
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

PrimaryNumber of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings During Combination Treatment Period

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
Reported as:: Count of participants · Participants

Number of Participants With Abnormal Clinically Significant Electrocardiogram (ECG) Findings During Combination Treatment Period
Participants	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Week 4, n=10,8,11,1	0	0	0	0
Week 8, n=8,9,8,0	0	1	1	—
Week 16, n=8,8,3,1	0	0	0	0
Week 24, n=5,5,3,1	0	0	0	0
Week 32, n=4,3,3,1	0	0	1	0
Week 40, n=1,0,2,1	0	—	0	0
Week 48, n=1,1,1,0	0	0	0	—
Week 56, n=1,0,1,0	0	—	0	—
Week 64, n=1,0,1,0	0	—	0	—
Week 72, n=0,0,1,0	—	—	0	—
Week 80, n=0,0,1,0	—	—	0	—
Week 88, n=0,0,1,0	—	—	0	—

PrimaryNumber 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

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
Reported as:: Count of participants · Participants

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
Participants	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
SBP, Any Grade Increase	8	6	5	1
SBP, Increase to Grade 2	3	1	3	0
SBP, Increase to Grade 3	3	2	1	0
DBP, Any Grade Increase	8	6	5	2
DBP, Increase to Grade 2	6	4	2	1
DBP, Increase to Grade 3	0	0	0	0

PrimaryNumber of Participants With Worst Case Post-Baseline Results for Heart Rate During Combination Treatment Period

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
Reported as:: Count of participants · Participants

Number of Participants With Worst Case Post-Baseline Results for Heart Rate During Combination Treatment Period
Participants	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Decrease to <60	2	2	6	1
Change to normal or no change	8	7	5	1
Increase to >100	1	3	1	1

PrimaryNumber of Participants With Worst Case Post-Baseline Results for Body Temperature During Combination Treatment Period

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
Reported as:: Count of participants · Participants

Number of Participants With Worst Case Post-Baseline Results for Body Temperature During Combination Treatment Period
Participants	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Decrease to <=35	0	0	0	0
Change to normal or no change	11	10	10	2
Increase to >=38	0	0	2	0

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

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
Reported as:: Number · Percentage of participants

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
Percentage of participants	GSK2636771 200mg/Enzalutamide 160mg - Overall
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	50

SecondaryProstate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate at 12 Weeks During Combination Treatment Period

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
Reported as:: Number · Percentage of participants

Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate at 12 Weeks During Combination Treatment Period
Percentage of participants	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Prostate-specific Antigen Decrease From Baseline >=50% (PSA50) Response Rate at 12 Weeks During Combination Treatment Period	9	9	8	50

SecondaryObjective Response Rate (ORR) During Combination Treatment Period

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
Reported as:: Number · Percentage of participants

Objective Response Rate (ORR) During Combination Treatment Period
Percentage of participants	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
CR	0	0	0	0
PR	9	0	0	0

SecondaryTime to PSA Progression According to PCWG2 Criteria During Combination Treatment Period

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
Reported as:: Median · Weeks

Time to PSA Progression According to PCWG2 Criteria During Combination Treatment Period
Weeks	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Time to PSA Progression According to PCWG2 Criteria During Combination Treatment Period	19.1 (15.1 to 31.1)	14.6 (11.3 to 19.1)	11.4 (11.1 to 19.1)	11.9 (NA to NA)

SecondaryTime to Radiological Progression According to PCWG2 Criteria During Combination Treatment Period

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
Reported as:: Median · Weeks

Time to Radiological Progression According to PCWG2 Criteria During Combination Treatment Period
Weeks	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Time to Radiological Progression According to PCWG2 Criteria During Combination Treatment Period	38.1 (34.3 to 38.1)	23.1 (11.3 to NA)	21.9 (14.6 to 43.0)	38.9 (NA to NA)

SecondaryRadiological Progression Free Survival (rPFS) Per PCWG2 Criteria During Combination Treatment Period

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
Reported as:: Median · Weeks

Radiological Progression Free Survival (rPFS) Per PCWG2 Criteria During Combination Treatment Period
Weeks	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 200mg/Enzalutamide 160mg Expansion	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
Radiological Progression Free Survival (rPFS) Per PCWG2 Criteria During Combination Treatment Period	38.1 (34.3 to 38.1)	23.1 (11.3 to NA)	21.9 (14.6 to 43.0)	38.9 (NA to NA)

SecondaryPlasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period

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
Reported as:: Mean · Nanograms per milliliter

Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Nanograms per milliliter	GSK2636771 200mg/Enzalutamide 160mg Expansion
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

SecondaryPlasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period

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
Reported as:: Mean · Nanograms per milliliter

Plasma Concentration of GSK2636771 in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Nanograms per milliliter	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
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	—

SecondaryPlasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period

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
Reported as:: Mean · Micrograms per milliliter

Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Micrograms per milliliter	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
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	—

SecondaryPlasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period

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
Reported as:: Mean · Micrograms per milliliter

Plasma Concentration of Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Micrograms per milliliter	GSK2636771 200mg/Enzalutamide 160mg Expansion
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

SecondaryPlasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period

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
Reported as:: Mean · Micrograms per milliliter

Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Escalation Cohorts in Combination Treatment Period
Micrograms per milliliter	GSK2636771 200mg/Enzalutamide 160mg Escalation	GSK2636771 300mg/Enzalutamide 160mg Escalation	GSK2636771 400mg/Enzalutamide 160mg Escalation
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	—

SecondaryPlasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period

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
Reported as:: Mean · Micrograms per milliliter

Plasma Concentration of N-desmethyl Enzalutamide in GSK2636771/Enzalutamide Expansion Cohort in Combination Treatment Period
Micrograms per milliliter	GSK2636771 200mg/Enzalutamide 160mg Expansion
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

Collected over Up to Week 2 for run-in period and up to maximum of 675 days for combination treatment period. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Enzalutamide Only (run-in Period)	0/37 (0%)	1/37 (2.7%)	11/37 (29.7%)
GSK2636771 200mg/Enzalutamide 160mg Escalation	0/11 (0%)	2/11 (18.2%)	11/11 (100%)
GSK2636771 200mg/Enzalutamide 160mg Expansion	0/11 (0%)	2/11 (18.2%)	11/11 (100%)
GSK2636771 300mg/Enzalutamide 160mg Escalation	0/12 (0%)	2/12 (16.7%)	12/12 (100%)
GSK2636771 400mg/Enzalutamide 160mg Escalation	0/2 (0%)	0/2 (0%)	2/2 (100%)

Most frequent serious events

Showing 10 of 11

Most frequent serious events
Event	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
Abdominal painGastrointestinal disorders	0/37	1/11	0/11	0/12	0/2
FallInjury, poisoning and procedural complications	0/37	1/11	0/11	0/12	0/2
Gastrointestinal haemorrhageGastrointestinal disorders	0/37	0/11	1/11	0/12	0/2
HaematuriaRenal and urinary disorders	0/37	0/11	1/11	0/12	0/2
HaemoptysisRespiratory, thoracic and mediastinal disorders	0/37	0/11	1/11	0/12	0/2
Muscular weaknessMusculoskeletal and connective tissue disorders	0/37	0/11	1/11	0/12	0/2
Acute kidney injuryRenal and urinary disorders	0/37	0/11	0/11	1/12	0/2
CellulitisInfections and infestations	0/37	0/11	0/11	1/12	0/2
HypocalcaemiaMetabolism and nutrition disorders	0/37	0/11	0/11	1/12	0/2
Pleural effusionRespiratory, thoracic and mediastinal disorders	0/37	0/11	0/11	1/12	0/2

Most frequent other events

Showing 10 of 128

Most frequent other events
Event	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
DiarrhoeaGastrointestinal disorders	1/37	6/11	8/11	7/12	2/2
AnaemiaBlood and lymphatic system disorders	0/37	3/11	1/11	5/12	1/2
HypocalcaemiaMetabolism and nutrition disorders	0/37	2/11	1/11	5/12	1/2
Blood creatinine increasedInvestigations	0/37	2/11	1/11	2/12	1/2
ArthralgiaMusculoskeletal and connective tissue disorders	1/37	1/11	2/11	1/12	1/2
ConstipationGastrointestinal disorders	0/37	2/11	1/11	1/12	1/2
Abdominal discomfortGastrointestinal disorders	0/37	0/11	2/11	0/12	1/2
HypomagnesaemiaMetabolism and nutrition disorders	0/37	0/11	1/11	1/12	1/2
LeukopeniaBlood and lymphatic system disorders	0/37	0/11	0/11	2/12	1/2
VomitingGastrointestinal disorders	0/37	0/11	2/11	0/12	1/2

Baseline characteristics

All Treated Safety Population consisted of all participants who received at least one dose of GSK2636771 or Enzalutamide.

Age, Customized
Age, Customized(Participants)	All Participants
<18 years	0
18-64 years	9
65-74 years	20
>=75 years	8

Sex: Female, Male
Sex: Female, Male(Participants)	All Participants
Female	0
Male	37

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	All Participants
African American/African Heritage	1
Asian-South East Asian Heritage	1
White-White/Caucasian/European Heritage	34
Native Hawaiian or Other Pacific Islander	1

Study locations

9 sites

GSK Investigational Site
Duarte, California 91010, United States
GSK Investigational Site
Los Angeles, California 90033, United States
GSK Investigational Site
Los Angeles, California 90095, United States
GSK Investigational Site
Washington, District of Columbia 20007, United States
GSK Investigational Site
Detroit, Michigan 48201, United States
GSK Investigational Site
New York, New York 10016, United States
GSK Investigational Site
Houston, Texas 77030, United States
GSK Investigational Site
London, SE1 9RT, United Kingdom
GSK Investigational Site
Sutton, SM2 5PT, United Kingdom

References and documents

Publications

Sarker D, Dawson NA, Aparicio AM, Dorff TB, Pantuck AJ, Vaishampayan UN, Henson L, Vasist L, Roy-Ghanta S, Gorczyca M, York W, Ganji G, Tolson J, de Bono JS. A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kbeta Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2021 Oct 1;27(19):5248-5257. doi: 10.1158/1078-0432.CCR-21-1115. PubMed 34281912 ↗

Study documents

Study protocol · Jan 27, 2017
Statistical analysis plan · Mar 3, 2020

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 22, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02215096
Lead sponsor: GlaxoSmithKline
Responsible party: Sponsor
First posted: Aug 13, 2014
Start date: Nov 13, 2014
Primary completion: Oct 3, 2019
Completion: Oct 3, 2019
Results posted: Oct 22, 2020
Last update: Oct 22, 2020

Study contacts

GSK Clinical Trials

study director · GlaxoSmithKline

Oversight

Data monitoring committee: No

View the source record on ClinicalTrials.gov ↗

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