Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzal... | NCT04191096

NCT04191096

Secondary IDs

ID	Type	Description
MK-3475-991	Other Identifier	MSD
KEYNOTE-991	Other Identifier	MSD
jRCT2080225171	Registry Identifier	jRCT
2023-507024-24-00	Registry Identifier	EU CT
U1111-1294-9592	Registry Identifier	UTN
2019-003633-41	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pembrolizumab + Enzalutamide + ADT	Experimental	Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.	Biological: Pembrolizumab Drug: Enzalutamide Drug: Androgen Deprivation Therapy (ADT)
Placebo + Enzalutamide + ADT	Placebo Comparator	Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.	Drug: Enzalutamide Drug: Androgen Deprivation Therapy (ADT) Other: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.	Pembrolizumab + Enzalutamide + ADT

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.	Up to approximately 32 months
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.	Up to approximately 32 months

Secondary Outcomes

Measure	Description	Time Frame
Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)	TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
Has metastatic disease assessed by investigator and verified by BICR by either ≥2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study treatment or have a history of bilateral orchiectomy
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
Has adequate organ function
Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex

Exclusion Criteria:

Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
Has an active infection (including tuberculosis) requiring systemic therapy
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
Has a history of seizure or any condition that may predispose to seizure
Has a history of loss of consciousness within 12 months of screening
Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
Has hypotension (systolic blood pressure <86 millimeters of mercury [mmHg]) or uncontrolled hypertension (systolic blood pressure >170 mmHg or diastolic blood pressure >105 mmHg) at the screening visit
Has a history of clinically significant ventricular arrhythmias
Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for >39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
Has received a live vaccine within 30 days prior to randomization
Has a "superscan" bone scan
Has had an allogenic tissue/solid organ transplant
Is expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
Has received any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer with the following exceptions:
1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel
2. May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization
3. For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization
4. Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Alaska Clinical Research Center ( Site 0274)		Anchorage	Alaska	99503	United States
Providence Alaska Medical Center ( Site 0276)

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
36705526	Derived	Gratzke C, Kwiatkowski M, De Giorgi U, Martins da Trindade K, De Santis M, Armstrong AJ, Niu C, Liu Y, Poehlein CH. KEYNOTE-991: pembrolizumab plus enzalutamide and androgen deprivation for metastatic hormone-sensitive prostate cancer. Future Oncol. 2023 Jan 27. doi: 10.2217/fon-2022-0776. Online ahead of print.

Label	URL
Merck Oncology Clinical Trial Information	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 15, 2023

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

All randomized participants.

Arm/Group Information

ID	Title	Description
BG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
BG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00067.6± 8.3 BG00167.6± 8.2 BG00267.6± 8.3

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0000 BG0010 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG000119 BG001112 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG00019 BG00113 BG002

Prior Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) at Baseline

Prior docetaxel usage was defined as up to 6 cycles of docetaxel therapy for mHSPC as long as final treatment administration was completed within 2 months of randomization and no evidence of disease progression during or after completion of therapy was noted. mHSPC was defined as histologically or cytologically confirmed prostate adenocarcinoma without small cell histology.

Yes= participants with confirmed prior docetaxel use at baseline.

No = participants with no prior docetaxel usage at baseline.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG00064 BG001

Presence of High-Volume Disease at Baseline

High volume disease was defined as presence of visceral metastases or ≥4 bone lesions with ≥1 beyond the vertebral bodies and pelvis.

Yes = presence of high-volume disease at baseline. No = absence of high-volume disease at baseline.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG000392 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to approximately 32 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Units	Counts
Participants	OG000626 OG001625

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)NA = Median, lower limit and upper limit of 95% CI for rPFS cannot be calculated at the time of last disease assessment due to insufficient number of participants with events. OG001NA(NA to NA)NA = Median, lower limit and upper limit of 95% CI for rPFS cannot be calculated at the time of last disease assessment due to insufficient number of participants with events.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.9467	A one-sided p-value was calculated using the log-rank test stratified by prior docetaxel for mHSPC (Yes/No) and presence of high-volume disease (Yes/No) with small strata.	Hazard Ratio (HR)	1.20			2-Sided	95	0.96	1.49			HR and associated 95% Confidence Interval (CI) were calculated using Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by prior docetaxel for mHSPC (Yes/No) and presence of high-volume disease (Yes/No).		Other

Primary

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to approximately 32 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)

TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to Approximately 32 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Time to First Symptomatic Skeletal-related Event (TTSSRE)

TTSSRE was the time from randomization to the first symptomatic skeletal-related event defined as: use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to Approximately 32 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Time to Prostate-specific Antigen (PSA) Progression

Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline. Time to PSA was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to Approximately 32 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR

The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to Approximately 32 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use

TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a >2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) For participants symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids; a >2-point change from baseline in the average BPI-SF Item 3 score and the average worst pain score >4 and no decrease in average opioid use. TTPP was calculated using the Kaplan-Meier method for censored data. Participants who had > 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.

All randomized participants who received at least one dose of study treatment, and who had at least 1 BPI-SF assessment

Posted

Median

95% Confidence Interval

Months

Up to Approximately 32 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001

Secondary

Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2)

PFS2 was defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first.

All randomized participants

Posted

Median

95% Confidence Interval

Months

Up to Approximately 32 months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Prostate-specific Antigen (PSA) Response Rate

PSA response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by >50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed >3 weeks from the original response.

All randomized participants who had a baseline PSA measurement and had data available for analysis

Posted

Number

95% Confidence Interval

Percentage of participants

Up to Approximately 32 Months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Prostate-specific Antigen (PSA) Undetectable

PSA undetectable rate was defined as the percentage of participants with detectable PSA (> 0.2 ng/mL) at baseline, which becomes undetectable (< 0.2 ng/mL) during study treatment.

All randomized participants with detectable PSA at baseline and had data available for analysis

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to Approximately 32 Months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR

ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on base scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).

All randomized participants with measurable disease at baseline and had data available for analysis

Posted

Number

95% Confidence Interval

Percentage of Participants

Up to Approximately 32 Months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR

DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of a least 5 mm. PD per PCWG was the appearance of >2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for >6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data.

All randomized participants who demonstrated a CR or PR, and had data available for analysis

Posted

Median

95% Confidence Interval

Months

Up to Approximately 32 Months

ID	Title	Description
OG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.
OG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.

Secondary

Number of Participants Who Experience an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Participants who experienced an AE will be reported for each arm.

Not Posted

Jun 2027

Up to Approximately 59 Months

Participants

Secondary

Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported for each arm.

Not Posted

Jun 2027

Up to Approximately 59 Months

Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab + Enzalutamide + ADT	Participants received 200 mg pembrolizumab IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily (QD), while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation were met.	105	626	252	625	588	625
EG001	Placebo + Enzalutamide + ADT	Participants received placebo IV on Day 1 of each 3-week cycle for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally QD, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants received enzalutamide and ADT until criteria for discontinuation are met.	93	625	145	625	551	625

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0005 events5 affected625 at risk EG0012 events2 affected625 at risk
Autoimmune haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0011 events1 affected625 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0002 events1 affected625 at risk EG0011 events1 affected625 at risk
Angina pectoris	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Angina unstable	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Aortic valve stenosis	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Arteriosclerosis coronary artery	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Atrial flutter	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Bradycardia	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Cardiac arrest	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0011 events1 affected625 at risk
Cardiac failure	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Cardiac ventricular thrombosis	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Coronary artery disease	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0013 events3 affected625 at risk
Immune-mediated myocarditis	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Myocardial infarction	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0007 events7 affected625 at risk EG0017 events7 affected625 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Myopericarditis	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Supraventricular tachyarrhythmia	Cardiac disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Hypophysitis	Endocrine disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Inappropriate antidiuretic hormone secretion	Endocrine disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Normal tension glaucoma	Eye disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Chronic gastritis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Colitis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0008 events7 affected625 at risk EG0010 events0 affected625 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0006 events5 affected625 at risk EG0012 events1 affected625 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Enlarged uvula	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Enteritis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Gastritis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Immune-mediated gastritis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Incarcerated inguinal hernia	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0004 events4 affected625 at risk EG0011 events1 affected625 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0019 events2 affected625 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0013 events1 affected625 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Asthenia	General disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Chest pain	General disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Condition aggravated	General disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Death	General disorders	MedDRA 25.1	Systematic Assessment	EG0006 events6 affected625 at risk EG0012 events2 affected625 at risk
Fatigue	General disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0013 events3 affected625 at risk
Injection site reaction	General disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Peripheral swelling	General disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Pyrexia	General disorders	MedDRA 25.1	Systematic Assessment	EG0005 events5 affected625 at risk EG0013 events3 affected625 at risk
Sudden death	General disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Bile duct stone	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0010 events0 affected625 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Hepatitis acute	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Hepatotoxicity	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0003 events2 affected625 at risk EG0010 events0 affected625 at risk
Hyperplastic cholecystopathy	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 25.1	Systematic Assessment	EG0005 events5 affected625 at risk EG0010 events0 affected625 at risk
Contrast media reaction	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Hypersensitivity	Immune system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Abdominal abscess	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Abdominal infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Appendicitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Bacterial sepsis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Bone tuberculosis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
COVID-19	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0006 events6 affected625 at risk EG0015 events5 affected625 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0004 events4 affected625 at risk EG0016 events6 affected625 at risk
Cellulitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0012 events1 affected625 at risk
Cholecystitis infective	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Cystitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Device related infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Diarrhoea infectious	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Diverticulitis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Erysipelas	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Gastroenteritis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Joint tuberculosis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Nosocomial infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Perineal abscess	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Pneumonia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG00010 events9 affected625 at risk EG0018 events7 affected625 at risk
Pneumonia legionella	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Post procedural infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Postoperative wound infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Pyelonephritis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0010 events0 affected625 at risk
Rash pustular	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Sepsis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0012 events2 affected625 at risk
Septic shock	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0010 events0 affected625 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG00016 events11 affected625 at risk EG0017 events7 affected625 at risk
Urosepsis	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0013 events3 affected625 at risk
Wound infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Craniocerebral injury	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Cystitis radiation	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Electric shock	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0013 events3 affected625 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0006 events6 affected625 at risk EG0012 events2 affected625 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Gun shot wound	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Head injury	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Joint dislocation	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0004 events3 affected625 at risk EG0011 events1 affected625 at risk
Muscle rupture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Soft tissue injury	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0010 events0 affected625 at risk
Spinal cord injury	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Toxicity to various agents	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Traumatic intracranial haemorrhage	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Blood glucose increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Neutrophil count decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Oxygen saturation decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Troponin I increased	Investigations	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0004 events4 affected625 at risk EG0010 events0 affected625 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Hypervolaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0011 events1 affected625 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Type 3 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Vitamin B1 deficiency	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0012 events2 affected625 at risk
Autoimmune myositis	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0013 events3 affected625 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Myopathy	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0011 events1 affected625 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0012 events2 affected625 at risk
Sarcopenia	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Spinal ligament ossification	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Spinal osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Adenocarcinoma of colon	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0012 events2 affected625 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Bladder neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Bladder transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0011 events1 affected625 at risk
Colorectal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Glottis carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Hepatic cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0002 events1 affected625 at risk EG0010 events0 affected625 at risk
Lung adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Neuroendocrine carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Neuroendocrine tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Pancreatic neuroendocrine tumour	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Rectal cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Squamous cell carcinoma of lung	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Tongue neoplasm malignant stage unspecified	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Tonsil cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Basal ganglia infarction	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Brain injury	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Brain oedema	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Cauda equina syndrome	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Cerebellar haemorrhage	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Cerebral infarction	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0012 events2 affected625 at risk
Dementia	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Dizziness	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Encephalopathy	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Facial nerve disorder	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Headache	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Nerve compression	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0002 events1 affected625 at risk EG0010 events0 affected625 at risk
Noninfective encephalitis	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Polyneuropathy	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Presyncope	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Progressive bulbar palsy	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Radiculopathy	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Sciatica	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Seizure	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Spinal cord compression	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0004 events3 affected625 at risk EG0015 events5 affected625 at risk
Syncope	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Toxic encephalopathy	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Device dislocation	Product Issues	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0013 events2 affected625 at risk
Device malfunction	Product Issues	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Confusional state	Psychiatric disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Depression	Psychiatric disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Mania	Psychiatric disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0004 events4 affected625 at risk EG0012 events1 affected625 at risk
Bladder diverticulum	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Calculus bladder	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Calculus urinary	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Dysuria	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Haematuria	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0014 events3 affected625 at risk
Haemorrhage urinary tract	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0002 events1 affected625 at risk EG0010 events0 affected625 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0011 events1 affected625 at risk
Immunotactoid glomerulonephritis	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Renal failure	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Renal impairment	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Tubulointerstitial nephritis	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Ureteric stenosis	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Urethral stenosis	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Urinary retention	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0014 events4 affected625 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Prostatic obstruction	Reproductive system and breast disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Testicular pain	Reproductive system and breast disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0013 events2 affected625 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0012 events2 affected625 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0012 events2 affected625 at risk
Hypersensitivity pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0004 events4 affected625 at risk EG0010 events0 affected625 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0007 events7 affected625 at risk EG0011 events1 affected625 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0012 events2 affected625 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0003 events3 affected625 at risk EG0010 events0 affected625 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Dermatitis exfoliative generalised	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0005 events5 affected625 at risk EG0010 events0 affected625 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0005 events5 affected625 at risk EG0010 events0 affected625 at risk
Drug reaction with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Eczema	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0005 events5 affected625 at risk EG0010 events0 affected625 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG00010 events10 affected625 at risk EG0011 events1 affected625 at risk
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG00010 events10 affected625 at risk EG0010 events0 affected625 at risk
Rash morbilliform	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Toxic skin eruption	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Aortic stenosis	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0011 events1 affected625 at risk
Embolism	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Hypertensive crisis	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Hypotension	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0002 events2 affected625 at risk EG0010 events0 affected625 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0001 events1 affected625 at risk EG0010 events0 affected625 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk
Phlebitis	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG0000 events0 affected625 at risk EG0011 events1 affected625 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.1	Systematic Assessment	EG000139 events97 affected625 at risk EG001108 events85 affected625 at risk
Hypothyroidism	Endocrine disorders	MedDRA 25.1	Systematic Assessment	EG00082 events82 affected625 at risk EG00125 events25 affected625 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG00041 events32 affected625 at risk EG00133 events29 affected625 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG000133 events108 affected625 at risk EG001117 events103 affected625 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG000196 events127 affected625 at risk EG00192 events73 affected625 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG000125 events105 affected625 at risk EG00186 events75 affected625 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.1	Systematic Assessment	EG00043 events35 affected625 at risk EG00136 events29 affected625 at risk
Asthenia	General disorders	MedDRA 25.1	Systematic Assessment	EG000101 events80 affected625 at risk EG00166 events55 affected625 at risk
Fatigue	General disorders	MedDRA 25.1	Systematic Assessment	EG000236 events194 affected625 at risk EG001200 events178 affected625 at risk
Oedema peripheral	General disorders	MedDRA 25.1	Systematic Assessment	EG00073 events67 affected625 at risk EG00154 events50 affected625 at risk
Pyrexia	General disorders	MedDRA 25.1	Systematic Assessment	EG00068 events63 affected625 at risk EG00131 events26 affected625 at risk
COVID-19	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG00076 events75 affected625 at risk EG00176 events75 affected625 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.1	Systematic Assessment	EG00043 events37 affected625 at risk EG00140 events31 affected625 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 25.1	Systematic Assessment	EG00051 events44 affected625 at risk EG00164 events53 affected625 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG00089 events73 affected625 at risk EG00139 events38 affected625 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG00093 events74 affected625 at risk EG00143 events39 affected625 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 25.1	Systematic Assessment	EG00049 events40 affected625 at risk EG00120 events18 affected625 at risk
Blood creatinine increased	Investigations	MedDRA 25.1	Systematic Assessment	EG00058 events36 affected625 at risk EG00129 events20 affected625 at risk
Weight decreased	Investigations	MedDRA 25.1	Systematic Assessment	EG00062 events57 affected625 at risk EG00125 events20 affected625 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG000107 events91 affected625 at risk EG00159 events52 affected625 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 25.1	Systematic Assessment	EG00090 events58 affected625 at risk EG00171 events51 affected625 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG000251 events181 affected625 at risk EG001208 events161 affected625 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG000114 events102 affected625 at risk EG001125 events113 affected625 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG00040 events39 affected625 at risk EG00136 events33 affected625 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG00063 events54 affected625 at risk EG00165 events50 affected625 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG00033 events32 affected625 at risk EG00123 events21 affected625 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25.1	Systematic Assessment	EG00081 events65 affected625 at risk EG00183 events66 affected625 at risk
Dizziness	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG00066 events59 affected625 at risk EG00153 events46 affected625 at risk
Dysgeusia	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG00039 events37 affected625 at risk EG00124 events23 affected625 at risk
Headache	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG00098 events79 affected625 at risk EG00181 events65 affected625 at risk
Paraesthesia	Nervous system disorders	MedDRA 25.1	Systematic Assessment	EG00028 events22 affected625 at risk EG00143 events41 affected625 at risk
Insomnia	Psychiatric disorders	MedDRA 25.1	Systematic Assessment	EG00071 events62 affected625 at risk EG00153 events47 affected625 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG00054 events51 affected625 at risk EG00151 events44 affected625 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.1	Systematic Assessment	EG00060 events51 affected625 at risk EG00125 events24 affected625 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG00056 events49 affected625 at risk EG00155 events48 affected625 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG000142 events110 affected625 at risk EG00173 events55 affected625 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG000200 events148 affected625 at risk EG00166 events58 affected625 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 25.1	Systematic Assessment	EG00061 events56 affected625 at risk EG00123 events15 affected625 at risk
Hot flush	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG000119 events110 affected625 at risk EG001148 events144 affected625 at risk
Hypertension	Vascular disorders	MedDRA 25.1	Systematic Assessment	EG000130 events108 affected625 at risk EG001155 events130 affected625 at risk

First MCP Posted Date

ID	Term
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
C582435	pembrolizumab
C540278	enzalutamide
D000726	Androgen Antagonists

Ancestor Terms

ID	Term
D006727	Hormone Antagonists
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D045505	Physiological Effects of Drugs
D020228	Pharmacologic Actions
D020164	Chemical Actions and Uses

Units	Counts
Participants	OG000626 OG001625

Units	Counts
Participants	OG000619 OG001617