A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo... | NCT02752074

NCT02752074

ID	Type	Description	Link
2015-004991-31	EudraCT Number

Status Module

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Oversight 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 + Epacadostat	Experimental	Pembrolizumab + Epacadostat	Drug: pembrolizumab + epacadostat
Pembrolizumab + Placebo	Active Comparator	Pembrolizumab + Placebo	Drug: pembrolizumab + placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
pembrolizumab + epacadostat	Drug	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1) Epacadostat will be administered orally daily starting at Day 1 (Week 1)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-free Survival	Progression-free survival, defined as the time from date of randomization until the earliest date of disease progression, as determined by independent central review of objective radiographic disease assessments per RECIST 1.1, or death from any cause, whichever comes first.	Assessed every 9 weeks for duration of study participation which is estimated to be 24 months
Overall Survival (OS) Rate at 6 Months	Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data.	Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated.

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR)	Objective response rate (ORR) is defined as the percentage of the participants in the analysis population who have a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 by independent central review.	Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

Eligibility Module

Name	Affiliation	Role
Mark Jones, MD	Incyte Corporation	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31221619	Derived	Long GV, Dummer R, Hamid O, Gajewski TF, Caglevic C, Dalle S, Arance A, Carlino MS, Grob JJ, Kim TM, Demidov L, Robert C, Larkin J, Anderson JR, Maleski J, Jones M, Diede SJ, Mitchell TC. Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study. Lancet Oncol. 2019 Aug;20(8):1083-1097. doi: 10.1016/S1470-2045(19)30274-8. Epub 2019 Jun 17.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
FG001	Pembrolizumab + Placebo

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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 18, 2018

Arm/Group Information

ID	Title	Description
BG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
BG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).
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, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
< 65 years	BG000183 BG001193 BG002376
≥ 65 years

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000137 BG001146 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00036 BG00127 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Eastern Cooperative Oncology Group (ECOG)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Fully active	BG000261 BG001267 BG002

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

Progression-free Survival

Progression-free survival, defined as the time from date of randomization until the earliest date of disease progression, as determined by independent central review of objective radiographic disease assessments per RECIST 1.1, or death from any cause, whichever comes first.

Intent to Treat (ITT) population: consists of all randomized participants.

Posted

Median

95% Confidence Interval

months

Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
OG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000354 OG001352

Title

Denominators

Categories

Title	Measurements
	OG0004.7(2.9 to 6.8) OG0014.9(2.9 to 6.8)

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		0.51711	One-sided p-value based on log-rank test.	Hazard Ratio (HR)	1.00			2-Sided	95	0.83	1.21					Other

Primary

Overall Survival (OS) Rate at 6 Months

Defined as time from date of randomization to date of death due to any cause. OS was calculated using product-limit (Kaplan-Meier) method for censored data.

Intent to Treat (ITT) population: consists of all randomized participants. OS was analyzed at the time of primary analysis at 6 months. An overall OS was not conducted after the primary analysis since all participants were unblinded, transitioned to monotherapy pembrolizumab and survival follow-up was discontinued.

Posted

Median

95% Confidence Interval

percent probability

Assessed every 9 weeks of study participation which is estimated to be 24 months. The OS rate at Month 6 was calculated.

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
OG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).

Units	Counts

Secondary

Objective Response Rate (ORR)

Objective response rate (ORR) is defined as the percentage of the participants in the analysis population who have a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 by independent central review.

Intent to Treat (ITT) population: consists of all randomized participants.

Posted

Count of Participants

Participants

Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
OG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000

Secondary

Safety and Tolerability, as Assessed by Percentage of Participants With Adverse Events

Safety and tolerability, as assessed by percentage of participants with adverse events and changes in laboratory parameters.

All Subjects as Treated (ASaT): All participants who were enrolled and took at least 1 dose of study medication.

Posted

Count of Participants

Participants

Through up to 90 days after end of treatment, up to 27 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
OG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000

Secondary

Duration of Response (DOR)

Defined as the time from the earliest date of qualifying response until earliest date of disease progression, per RECIST v1.1, or death from any cause, whichever comes first. Includes participants with complete response or partial response.

Intent to Treat (ITT) population: consists of all randomized participants.

Posted

Median

Full Range

months

Assessed every 9 weeks for duration of study participation which is estimated to be 24 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
OG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000

Secondary

Apparent Oral Clearance (CL/F) of Epacadostat

Defined as oral dose clearance.

All randomized participants enrolled in the Epacadostat arm currently with melanoma.

Posted

Mean

Standard Deviation

Liter/hour (L/h)

Through up to 30 days after the end of treatment, up to 25 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000340

Secondary

Apparent Volume of Distribution (Vd/F) of Epacadostat

Apparent volume of distribution after administration.

All randomized participants enrolled in the Epacadostat arm currently with melanoma.

Posted

Mean

Standard Deviation

Liter

Through up to 30 days after the end of treatment, up to 25 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000

Secondary

Clearance (CL) of Pembrolizumab

The data was not available nor was the analysis completed for pembrolizumab CL, because participants were unblinded and sample collections and the planned analysis for pembrolizumab CL were discontinued after the interim analysis.

Posted

Through up to 30 days after the end of treatment, up to 25 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
OG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000

Secondary

Volume of Distribution (V) of Pembrolizumab

The data was not available nor was the analysis completed for pembrolizumab V, because participants were unblinded and sample collections and the planned analysis for pembrolizumab V were discontinued after the interim analysis.

Posted

Through up to 30 days after the end of treatment, up to 25 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
OG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000

Secondary

Formation of Anti-pembrolizumab Antibodies

Evaluate the measurement of anti-drug antibodies (ADA).

Data was not available nor the analysis completed for the incidence of ADA to pembrolizumab, because all participants were unblinded; sample collections and the planned analysis for ADA were discontinued after the interim analysis.

Posted

Through up to 30 days after the end of treatment, up to 25 months

ID	Title	Description
OG000	Pembrolizumab + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).
OG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).

Units	Counts
Participants	OG000

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 + Epacadostat	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Epacadostat will be administered orally daily starting at Day 1 (Week 1).	147	353	99	353	327	353
EG001	Pembrolizumab + Placebo	Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1). Placebo will be administered orally daily starting at Day 1 (Week 1).	136	352	100	352	325	352

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0014 affected352 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Extrasystoles	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Myocarditis	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Vertigo positional	Ear and labyrinth disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected353 at risk EG0011 affected352 at risk
Hypophysitis	Endocrine disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0013 affected352 at risk
Hypothyroidism	Endocrine disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0011 affected352 at risk
Autoimmune colitis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Colitis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected353 at risk EG0015 affected352 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0009 affected353 at risk EG0014 affected352 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Gastritis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Intussusception	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Large intestinal obstruction	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0012 affected352 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Pancreatitis chronic	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0012 affected352 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0003 affected353 at risk EG0011 affected352 at risk
Asthenia	General disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Chest pain	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Death	General disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0010 affected352 at risk
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0012 affected352 at risk
General physical health deterioration	General disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG0004 affected353 at risk EG0013 affected352 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0010 affected352 at risk
Bile duct obstruction	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Hepatitis acute	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Cytokine release syndrome	Immune system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Drug hypersensitivity	Immune system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Cellulitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Dacryocanaliculitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Erysipelas	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Infected skin ulcer	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Peritonitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Pneumonia	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0005 affected353 at risk EG0010 affected352 at risk
Pseudomonas infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Rhinitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Sepsis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0012 affected352 at risk
Septic shock	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0012 affected352 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Urosepsis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Viral infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Wound infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Pubis fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Radiation necrosis	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Thoracic vertebral fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Wound complication	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Blood creatinine increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0011 affected352 at risk
Blood potassium increased	Investigations	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0012 affected352 at risk
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0011 affected352 at risk
Dupuytren's contracture	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Polymyalgia rheumatica	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Scleroderma	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0014 affected352 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0003 affected353 at risk EG0013 affected352 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
T-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0012 affected352 at risk
Tumour flare	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Chronic inflammatory demyelinating polyradiculoneuropathy	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Generalised tonic-clonic seizure	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0015 affected352 at risk
Hemiplegia	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Ischaemic cerebral infarction	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Neuralgia	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Presyncope	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0012 affected352 at risk
Syncope	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0012 affected352 at risk
Tension headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Anxiety	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Paranoia	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0013 affected352 at risk
Bladder outlet obstruction	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Nephritis	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Renal failure	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Renal injury	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0011 affected352 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Pneumonia aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0010 affected352 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0005 affected353 at risk EG0013 affected352 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0012 affected352 at risk
Pulmonary infarction	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Dermatitis exfoliative	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Drug reaction with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0012 affected352 at risk
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Lichen planus	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0002 affected353 at risk EG0010 affected352 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Essential hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Haematoma	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Hypotension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0012 affected352 at risk
Lymphoedema	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Retinopathy	Eye disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Colitis ischaemic	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0011 affected352 at risk
Lung infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Concussion	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Carcinoid tumour of the gastrointestinal	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Follicular thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Intestinal adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Optic neuritis	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Seizure	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Bladder perforation	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Haematuria	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Nephrotic syndrome	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Tubulointerstitial nephritis	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Emphysema	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Thrombosis	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 20.1	Systematic Assessment	EG0001 affected353 at risk EG0010 affected352 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk
Haemarthrosis	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG0000 affected353 at risk EG0011 affected352 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 20.1	Systematic Assessment	EG00035 affected353 at risk EG00136 affected352 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 20.1	Systematic Assessment	EG00022 affected353 at risk EG00127 affected352 at risk
Hypothyroidism	Endocrine disorders	MedDRA 20.1	Systematic Assessment	EG00044 affected353 at risk EG00135 affected352 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00037 affected353 at risk EG00137 affected352 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00024 affected353 at risk EG00116 affected352 at risk
Constipation	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00058 affected353 at risk EG00162 affected352 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00090 affected353 at risk EG001100 affected352 at risk
Dry mouth	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00019 affected353 at risk EG00130 affected352 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG000103 affected353 at risk EG00186 affected352 at risk
Vomiting	Gastrointestinal disorders	MedDRA 20.1	Systematic Assessment	EG00051 affected353 at risk EG00144 affected352 at risk
Asthenia	General disorders	MedDRA 20.1	Systematic Assessment	EG00068 affected353 at risk EG00146 affected352 at risk
Fatigue	General disorders	MedDRA 20.1	Systematic Assessment	EG000100 affected353 at risk EG00194 affected352 at risk
Oedema peripheral	General disorders	MedDRA 20.1	Systematic Assessment	EG00027 affected353 at risk EG00127 affected352 at risk
Pyrexia	General disorders	MedDRA 20.1	Systematic Assessment	EG00046 affected353 at risk EG00138 affected352 at risk
Nasopharyngitis	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG00050 affected353 at risk EG00150 affected352 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG00019 affected353 at risk EG00133 affected352 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG00020 affected353 at risk EG00132 affected352 at risk
Alanine aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG00039 affected353 at risk EG00125 affected352 at risk
Amylase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG00027 affected353 at risk EG00134 affected352 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG00036 affected353 at risk EG00133 affected352 at risk
Lipase increased	Investigations	MedDRA 20.1	Systematic Assessment	EG00036 affected353 at risk EG00139 affected352 at risk
Weight decreased	Investigations	MedDRA 20.1	Systematic Assessment	EG00022 affected353 at risk EG00117 affected352 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG00055 affected353 at risk EG00144 affected352 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.1	Systematic Assessment	EG00023 affected353 at risk EG00117 affected352 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG00063 affected353 at risk EG00163 affected352 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG00047 affected353 at risk EG00152 affected352 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG00026 affected353 at risk EG00132 affected352 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.1	Systematic Assessment	EG00032 affected353 at risk EG00128 affected352 at risk
Dizziness	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG00033 affected353 at risk EG00132 affected352 at risk
Headache	Nervous system disorders	MedDRA 20.1	Systematic Assessment	EG00066 affected353 at risk EG00174 affected352 at risk
Anxiety	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG00019 affected353 at risk EG00114 affected352 at risk
Insomnia	Psychiatric disorders	MedDRA 20.1	Systematic Assessment	EG00035 affected353 at risk EG00131 affected352 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG00073 affected353 at risk EG00163 affected352 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.1	Systematic Assessment	EG00022 affected353 at risk EG00129 affected352 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG00023 affected353 at risk EG00123 affected352 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG00083 affected353 at risk EG001101 affected352 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG00077 affected353 at risk EG00181 affected352 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG00021 affected353 at risk EG00118 affected352 at risk
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA 20.1	Systematic Assessment	EG00051 affected353 at risk EG00148 affected352 at risk
Hypertension	Vascular disorders	MedDRA 20.1	Systematic Assessment	EG00027 affected353 at risk EG00121 affected352 at risk
Influenza	Infections and infestations	MedDRA 20.1	Systematic Assessment	EG00019 affected353 at risk EG00117 affected352 at risk
Influenza like Illness	General disorders	MedDRA 20.1	Systematic Assessment	EG00017 affected353 at risk EG00122 affected352 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Birmingham	Alabama		United States

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D009371	Neoplasms by Site
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases