A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A An... | NCT00554229

ID	Type	Description	Link
2007-003227-20	EudraCT Number

Label	Type	Description	Intervention Names
ZD4054	Experimental	ZD4054 10 mg oral tablet once daily	Drug: ZD4054
Placebo	Placebo Comparator	Matching Placebo, oral tablets once daily	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
ZD4054	Drug	ZD4054 10 mg oral tablet once daily	ZD4054	Zibotentan

Measure	Description	Time Frame
Overall Survival	Median time (in months) from randomisation until death using the Kaplan-Meier method	From date of randomization until date of death, assessed up to 32 months

Measure	Description	Time Frame
Progression Free Survival	Median time (in months) from randomisation until clinical progression of disease, where progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline, using the Kaplan-Meier method	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 31 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients who answer TRUE to the following criteria may be eligible to participate in this trial.

Confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) that has spread to the bone (bone metastases)
Increasing Prostate Specific Antigen (PSA) over a one month period
No pain, or mild pain from prostate cancer
Currently receiving treatment with surgical or medical castration

Exclusion Criteria:

Patients who answer TRUE to the following may NOT eligible to participate in this trial.

Currently using opiates based pain killers)
Previous treatment with chemotherapy (paclitaxel, docetaxel, and mitoxantrone)
Suffering from heart failure or had a myocardial infarction within last 6 months
A history of epilepsy or seizures

Name	Affiliation	Role
Martin Gleave, MD, FRCSC, FACS	The Prostate Centre at Vancouver General Hospital	Principal Investigator
Joel B Nelson, MD	University of Pittsburgh	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Tucson	Arizona		United States
Research Site

ID	Title	Description
FG000	ZD4054	ZD4054 10 mg oral tablet once daily
FG001	Placebo	Placebo oral tablet once daily

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

Overall Survival

Median time (in months) from randomisation until death using the Kaplan-Meier method

Posted

Median

Full Range

months

From date of randomization until date of death, assessed up to 32 months

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000299 OG001295

Title

Denominators

Categories

Title	Measurements
	OG00024.5(0.5 to 31.2) OG00122.5(0.5 to 29.8)

Secondary

Progression Free Survival

Median time (in months) from randomisation until clinical progression of disease, where progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline, using the Kaplan-Meier method

Posted

Median

Inter-Quartile Range

Months

From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 31 months

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000

Secondary

Time to Use of Opiates

Median time (in months) from randomisation until use of opiates for disease-related symptoms for a duration ≥1 week using the Kaplan-Meier method

Posted

Median

Inter-Quartile Range

Months

From date of randomization until use of opiates for disease-related symptoms for a duration ≥1 week, assessed up to 31 months

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000

Secondary

Incidence of Skeletal Related Events

Median time (in months) from randomisation until occurrence of a skeletal related event, where skeletal related event is defined as the first occurrence of a pathological fracture, a vertebral compression fracture not related to trauma, prophylactic surgery or radiation for impending fracture or spinal cord compression, or a spinal cord compression, using the Kaplan-Meier method.

Posted

Median

Inter-Quartile Range

Months

From date of randomization until occurrence of a skeletal related event, assessed up to 31 months

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000

Secondary

Bone Metastases Formation

Median time (in months) from randomisation to appearance of ≥4 new bone lesions using the Kaplan-Meier method

Posted

Median

Inter-Quartile Range

Months

Patients were assessed every 12 weeks

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000

Secondary

Health Related Quality of Life

Median time (in months) from randomisation until deterioration of Health related Quality of Life using the Kaplan-Meier method, where deterioration is defined as a change from baseline of less than or equal to -6 points in Total FACT-P score maintained for 2 consecutive visits.

Posted

Median

Inter-Quartile Range

Months

Patients were assessed at every visit

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000

Secondary

Time to Prostate-specific Antigen (PSA) Progression

Median time (in months) from randomisation to first PSA value >50% higher than baseline of at least 5ng/ml seen in at least 2 consecutive PSA values at least 2 weeks apart using the Kaplan-Meier method.

Posted

Median

Inter-Quartile Range

Months

Patients were assessed every 12 weeks

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000

Secondary

Time to Pain Progression

Median time (in months) from randomisation to first assessment of an increased pain event, where increased pain event is defined as the first of a patient requiring opiate medication for duration of ≥1 week for pain due to prostate cancer metastasis, pain due to metastasis that has an increase in the worst pain item of the Brief Pain Inventory (BPI) from baseline to a minimum score of 5 with no decrease in analgesic use, or pain due to metastasis requiring radionuclide therapy, radiation therapy or surgery.

Posted

Median

Inter-Quartile Range

Months

Patients were assessed every 12 weeks

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000

Secondary

Time to Initiation of Chemotherapy

Median time (in months) from randomisation to first administration of any chemotherapy using the Kaplan-Meier method

Posted

Median

Inter-Quartile Range

Months

Patients were assessed every 12 weeks

ID	Title	Description
OG000	ZD4054	ZD4054 10 mg oral tablet once daily
OG001	Placebo	Placebo oral tablet once daily

Units	Counts
Participants	OG000

Secondary

Pharmacokinetic Characteristics of ZD4054

Not Posted

Least Squares Mean

95% Confidence Interval

Plasma concentration versus time

PK samples were performed at randomisation, Week 4, Week 8 and Week 12

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0006 affected298 at risk EG0011 affected295 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0013 affected295 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0013 affected295 at risk
Bone Marrow Failure	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Disseminated Intravascular Coagulation	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Cardiac Failure	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0006 affected298 at risk EG0010 affected295 at risk
Myocardial Infarction	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected298 at risk EG0012 affected295 at risk
Acute Myocardial Infarction	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0010 affected295 at risk
Left Ventricular Failure	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Angina Unstable	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Atrial Fibrillation	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Atrial Flutter	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Atrioventricular Block	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Atrioventricular Block Complete	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Cardiac Failure Acute	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Cardiac Failure Congestive	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Cardio-Respiratory Arrest	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Coronary Artery Stenosis	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Myocardial Ischaemia	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Prinzmetal Angina	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Right Ventricular Failure	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Sick Sinus Syndrome	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Supraventricular Tachycardia	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Ventricular Tachycardia	Cardiac disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Sudden Hearing Loss	Ear and labyrinth disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Cataract	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Retinal Detachment	Eye disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected298 at risk EG0011 affected295 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0012 affected295 at risk
Abdominal Hernia	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Abdominal Pain	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Ascites	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Colitis Ulcerative	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Colonic Polyp	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Duodenal Ulcer Perforation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Erosive Oesophagitis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Gastric Haemorrhage	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Gastric Ulcer	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Gastric Ulcer Haemorrhage	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Gastritis Haemorrhagic	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Gastrointestinal Haemorrhage	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Melaena	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Pancreatitis Acute	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Peptic Ulcer Perforation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Retroperitoneal Haemorrhage	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Death	General disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0017 affected295 at risk
Pyrexia	General disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected298 at risk EG0012 affected295 at risk
Disease Progression	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0012 affected295 at risk
Oedema Peripheral	General disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0010 affected295 at risk
Asthenia	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Chest Discomfort	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Chest Pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Fatigue	General disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
General Physical Health Deterioration	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Malaise	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Multi-Organ Failure	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Non-Cardiac Chest Pain	General disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0012 affected295 at risk
Bile Duct Obstruction	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Bile Duct Stone	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Cholangitis	Hepatobiliary disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Pneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0006 affected298 at risk EG0011 affected295 at risk
Sepsis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0003 affected298 at risk EG0013 affected295 at risk
Bronchopneumonia	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0010 affected295 at risk
Respiratory Tract Infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0012 affected295 at risk
Septic Shock	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0012 affected295 at risk
Abscess Jaw	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Appendicitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Bronchitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Cellulitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Gastroenteritis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Infected Cyst	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Lower Respiratory Tract Infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Lung Infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Meningitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Necrotising Fasciitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Oesophageal Candidiasis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Post Procedural Infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Staphylococcal Infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Urosepsis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Viral Pericarditis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Hip Fracture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0012 affected295 at risk
Subdural Haematoma	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0011 affected295 at risk
Cerebral Haemorrhage Traumatic	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Cervical Vertebral Fracture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Cystitis Radiation	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Femoral Neck Fracture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Fibula Fracture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Splenic Rupture	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Subcutaneous Haematoma	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Therapeutic Agent Toxicity	Injury, poisoning and procedural complications	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0012 affected295 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Diabetes Mellitus	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Gout	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Muscular Weakness	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0012 affected295 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Intervertebral Disc Protrusion	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Osteonecrosis Of Jaw	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Pathological Fracture	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Acute Myeloid Leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Bladder Transitional Cell Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Colon Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Gastric Cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Lung Neoplasm Malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Metastases To Spine	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Neoplasm Progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Oesophageal Carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Oesophageal Neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Cerebrovascular Accident	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected298 at risk EG0012 affected295 at risk
Transient Ischaemic Attack	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0012 affected295 at risk
Cerebral Haemorrhage	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Cerebral Infarction	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Cerebral Ischaemia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Cerebral Thrombosis	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Cerebrovascular Disorder	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Convulsion	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Lethargy	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Loss Of Consciousness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Neuropathy Peripheral	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Paraesthesia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Spinal Cord Compression	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Trigeminal Neuralgia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Vith Nerve Paralysis	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Completed Suicide	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Delirium	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Suicide Attempt	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Renal Failure Acute	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0014 affected295 at risk
Urinary Retention	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0003 affected298 at risk EG0010 affected295 at risk
Renal Failure	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0012 affected295 at risk
Anuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Haematuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Haemorrhage Urinary Tract	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Urethral Stenosis	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Benign Prostatic Hyperplasia	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Priapism	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Prostatic Haemorrhage	Reproductive system and breast disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Pulmonary Embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0005 affected298 at risk EG0012 affected295 at risk
Pleural Effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0004 affected298 at risk EG0010 affected295 at risk
Chronic Obstructive Pulmonary Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0013 affected295 at risk
Pneumonia Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0013 affected295 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0012 affected295 at risk
Pulmonary Oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0002 affected298 at risk EG0011 affected295 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Interstitial Lung Disease	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Obstructive Airways Disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Pulmonary Hypertension	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Upper Respiratory Tract Inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Decubitus Ulcer	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Deep Vein Thrombosis	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0012 affected295 at risk
Aortic Dissection	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Arteriosclerosis	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Haematoma	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0011 affected295 at risk
Iliac Artery Occlusion	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Lymphoedema	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0001 affected298 at risk EG0010 affected295 at risk
Phlebitis	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk
Venous Thrombosis Limb	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG0000 affected298 at risk EG0011 affected295 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG00046 affected298 at risk EG00133 affected295 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.0	Systematic Assessment	EG00011 affected298 at risk EG00116 affected295 at risk
Nausea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00062 affected298 at risk EG00144 affected295 at risk
Constipation	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00061 affected298 at risk EG00151 affected295 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00028 affected298 at risk EG00146 affected295 at risk
Vomiting	Gastrointestinal disorders	MedDRA 13.0	Systematic Assessment	EG00034 affected298 at risk EG00123 affected295 at risk
Oedema Peripheral	General disorders	MedDRA 13.0	Systematic Assessment	EG000132 affected298 at risk EG00156 affected295 at risk
Fatigue	General disorders	MedDRA 13.0	Systematic Assessment	EG00058 affected298 at risk EG00152 affected295 at risk
Pyrexia	General disorders	MedDRA 13.0	Systematic Assessment	EG00030 affected298 at risk EG00122 affected295 at risk
Asthenia	General disorders	MedDRA 13.0	Systematic Assessment	EG00018 affected298 at risk EG00122 affected295 at risk
Rhinitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00035 affected298 at risk EG00113 affected295 at risk
Nasopharyngitis	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00028 affected298 at risk EG00125 affected295 at risk
Urinary Tract Infection	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00019 affected298 at risk EG00124 affected295 at risk
Weight Decreased	Infections and infestations	MedDRA 13.0	Systematic Assessment	EG00015 affected298 at risk EG00113 affected295 at risk
Decreased Appetite	Metabolism and nutrition disorders	MedDRA 13.0	Systematic Assessment	EG00044 affected298 at risk EG00137 affected295 at risk
Back Pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00035 affected298 at risk EG00137 affected295 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00031 affected298 at risk EG00132 affected295 at risk
Pain In Extremity	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00022 affected298 at risk EG00123 affected295 at risk
Musculoskeletal Pain	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00015 affected298 at risk EG00119 affected295 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 13.0	Systematic Assessment	EG00012 affected298 at risk EG00116 affected295 at risk
Headache	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG00092 affected298 at risk EG00137 affected295 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG00017 affected298 at risk EG0018 affected295 at risk
Dizziness	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG00014 affected298 at risk EG00116 affected295 at risk
Dysgeusia	Nervous system disorders	MedDRA 13.0	Systematic Assessment	EG00011 affected298 at risk EG00117 affected295 at risk
Insomnia	Psychiatric disorders	MedDRA 13.0	Systematic Assessment	EG00024 affected298 at risk EG00119 affected295 at risk
Haematuria	Renal and urinary disorders	MedDRA 13.0	Systematic Assessment	EG00020 affected298 at risk EG00119 affected295 at risk
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG00048 affected298 at risk EG0019 affected295 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG00032 affected298 at risk EG00120 affected295 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 13.0	Systematic Assessment	EG00017 affected298 at risk EG00117 affected295 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 13.0	Systematic Assessment	EG00024 affected298 at risk EG00119 affected295 at risk
Hypertension	Vascular disorders	MedDRA 13.0	Systematic Assessment	EG00011 affected298 at risk EG00119 affected295 at risk

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Title	Description
BG000	ZD4054	ZD4054 10 mg oral tablet once daily
BG001	Placebo	Placebo oral tablet once daily
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	ZD4054	ZD4054 10 mg oral tablet once daily			98	298	257	298
EG001	Placebo	Placebo oral tablet once daily			105	295	221	295