ENTHUSE M0: A Phase III Trial of ZD4054 (Zibotentan) (Endothelin A Antagonist) in Non-metastatic Hormone Resistant Prostate Cancer

• Sponsor: AstraZeneca (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00626548
• Collaborator: (none)
• Enrollment: 2,577
• Locations: 330
• Arms: 2
• Duration (Months): 40
• Patients Per Site: 7.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Enthuse M0 is a large phase III clinical trial studying the efficacy of ZD4054 (Zibotentan) in hormone resistant prostate cancer (HRPC).

This clinical trial will test if the Endothelin A Receptor Antagonist ZD4054 (Zibotentan) can improve progression-free survival and overall survival against a background of existing prostate cancer treatments.

ZD4054 (Zibotentan) is a new type of agent, which is thought to slow tumour growth and spread by blocking Endothelin receptor activity. This trial will look at the effects of ZD4054 (Zibotentan) in hormone resistant prostate cancer (HRPC) patients who have had rising PSA after surgical or medical castration but have no evidence of metastases.

All patients participating in this clinical trial will receive existing prostate cancer treatments in addition to trial therapy.

Half the patients will receive ZD4054 (Zibotentan) , and half the patients will receive placebo in addition to standard prostate cancer therapy. By participating in this trial there is a 50% chance that patients will receive an agent that may slow the progression of the tumour.

No patients will be deprived of standard prostate cancer therapy.

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: ZD4054; Drug: Palcebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 2577 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase III, Randomised, Placebo-controlled, Double-blind Study to Assess the Efficacy and Safety of Once-daily Orally Administered ZD4054 (Zibotentan) 10 mg in Non-metastatic Hormone-resistant Prostate Cancer Patients
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Jan 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Matching Placebo	Drug: Palcebo; Matching Plcebo oral tablet once daily
Experimental: ZD4054 ZD4054 (Zibotentan)	Drug: ZD4054; 10 mg once daily oral dose; Other Names: Zibotentan

Outcome Measures

Primary Outcome Measures

1. Overall Survival [From date of randomization until date of death, assessed up to 33 months]

   Number of participants who have died at early analysis data cut off (DCO)

2. Progression Free Survival [Participants were followed up for progression every 4 weeks for the first 16 weeks then every 16 weeks]

   Number of participants who have a progression event at the early analysis DCO, 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

Secondary Outcome Measures

1. Health Related Quality of Life [Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks]

2. Time to Prostate-specific Antigen (PSA) Progression [Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks]

3. Time to Symptomatic Progression [Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

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

• Confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) that has NOT spread to the other parts of the body (metastases). Patients with lymph node involvement may be eligible if specified criteria is met.

• Increasing Prostate Specific Antigen (PSA), collected within one year of enrollment

• Currently receiving treatment with surgical or medical castration

Exclusion Criteria:

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

• Currently using opiate based pain killers for cancer related pain

• Previous treatment with chemotherapy (paclitaxel, docetaxel, and mitoxantrone). Prior targeted cancer therapies are permitted if received during a previous clinical trial

• Suffering from heart failure or had a myocardial infarction within last 6 months

• A history of epilepsy or seizures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Tucson	Arizona	United States
2	Research Site	Greenbrae	California	United States
3	Research Site	Los Angeles	California	United States
4	Research Site	San Diego	California	United States
5	Research Site	San Francisco	California	United States
6	Research Site	Denver	Colorado	United States
7	Research Site	Norwich	Connecticut	United States
8	Research Site	Washington	District of Columbia	United States
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10	Research Site	Miami	Florida	United States
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263	Research Site	Arequipa		Peru
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275	Research Site	Timisoara	Timis	Romania
276	Research Site	Bucuresti		Romania
277	Research Site	Cluj-Napoca		Romania
278	Research Site	Omsk	Omsk region	Russian Federation
279	Research Site	Izhevsk	Russia	Russian Federation
280	Research Site	Tomsk	Tomsk Region	Russian Federation
281	Research Site	Barnaul		Russian Federation
282	Research Site	Kursk		Russian Federation
283	Research Site	Moscow		Russian Federation
284	Research Site	Sochi		Russian Federation
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286	Research Site	Voronezh		Russian Federation
287	Research Site	Belgrade		Serbia
288	Research Site	Nis		Serbia
289	Research Site	Novi Sad		Serbia
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291	Research Site	Tygerberg	Cape Town	South Africa
292	Research Site	Overport	Durban	South Africa
293	Research Site	Parktown	Johannesburg	South Africa
294	Research Site	Pietermaritzburg		South Africa
295	Research Site	Pretoria		South Africa
296	Research Site	Elche	Alicante	Spain
297	Research Site	Barakaldo	Bizkaia	Spain
298	Research Site	Bilbao	Vizcaya	Spain
299	Research Site	A Corunna		Spain
300	Research Site	Barcelona		Spain
301	Research Site	Madrid		Spain
302	Research Site	Sevilla		Spain
303	Research Site	Valencia		Spain
304	Research Site	Gothenburg		Sweden
305	Research Site	Helsingborg		Sweden
306	Research Site	Jonkoping		Sweden
307	Research Site	Orebro		Sweden
308	Research Site	Stockholm		Sweden
309	Research Site	Uppsala		Sweden
310	Research Site	Aarau		Switzerland
311	Research Site	CH-4031 Basel		Switzerland
312	Research Site	Locarno		Switzerland
313	Research Site	Zuerich		Switzerland
314	Research Site	Taipei		Taiwan
315	Research Site	Ankara		Turkey
316	Research Site	Istanbul		Turkey
317	Research Site	Izmir		Turkey
318	Research Site	Reading	Berkshire	United Kingdom
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321	Research Site	Maidstone	Kent	United Kingdom
322	Research Site	Guildford	Surrey	United Kingdom
323	Research Site	Cambridge		United Kingdom
324	Research Site	Coventry		United Kingdom
325	Research Site	Glasgow		United Kingdom
326	Research Site	Huddersfield		United Kingdom
327	Research Site	Liverpool		United Kingdom
328	Research Site	London		United Kingdom
329	Research Site	Manchester		United Kingdom
330	Research Site	Newcastle upon Tyne		United Kingdom

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Kurt Miller, Prof., M.D., Charite University, Berlin, Germany
• Principal Investigator: Tia Higano, MD, University of Washington

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00626548
• Other Study ID Numbers: D4320C00015
• First Posted: Feb 29, 2008
• Last Update Posted: Sep 3, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by AstraZeneca: Hormone Resistant Prostate Cancer; Endothelin A Receptor Antagonist; Endothelin A; Endothelin A antagonist
• Additional relevant MeSH terms: Prostatic Neoplasms

Study Results

Participant Flow

Recruitment Details	2577 patients with hormone-resistant prostate cancer patients and bone metastasis were recruited between 15th January 2008 and 3rd May 2011
Pre-assignment Detail	1156 of the 2577 enrolled patients were not randomised to treatment groups as they failed screening

Arm/Group Title	ZD4054	Placebo
Arm/Group Description	ZD4054 10 mg oral tablet once daily	Placebo oral tablet once daily
Period Title: Overall Study
STARTED	705	716
Patients Received Treatment	703	712
COMPLETED	0	0
NOT COMPLETED	705	716

Baseline Characteristics

Arm/Group Title	ZD4054	Placebo	Total
Arm/Group Description	ZD4054 10 mg oral tablet once daily	Placebo oral tablet once daily	Total of all reporting groups
Overall Participants	705	716	1421
Age (years) [Mean (Standard Deviation) ]
Overall	72.4 (7.8)	72.5 (7.8)	72.45 (7.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	705 100%	716 100%	1421 100%

Outcome Measures

1. Primary Outcome

Title	Overall Survival
Description	Number of participants who have died at early analysis data cut off (DCO)
Time Frame	From date of randomization until date of death, assessed up to 33 months

Outcome Measure Data

Analysis Population Description

The analysis population only includes patients recruited by the time of the early analysis (1 October 2010)

Arm/Group Title	ZD4054	Placebo
Arm/Group Description	ZD4054 10 mg oral tablet once daily	Placebo oral tablet once daily
Measure Participants	592	589
Number [Participants]	40 5.7%	39 5.4%

2. Primary Outcome

Title	Progression Free Survival
Description	Number of participants who have a progression event at the early analysis DCO, 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
Time Frame	Participants were followed up for progression every 4 weeks for the first 16 weeks then every 16 weeks

Outcome Measure Data

Analysis Population Description

The analysis population only includes patients recruited by the time of the early analysis (1 October 2010)

Arm/Group Title	ZD4054	Placebo
Arm/Group Description	ZD4054 10 mg oral tablet once daily	Placebo oral tablet once daily
Measure Participants	592	589
Number [Participants]	131 18.6%	162 22.6%

3. Secondary Outcome

Title	Health Related Quality of Life
Time Frame	Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Time to Prostate-specific Antigen (PSA) Progression
Time Frame	Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Time to Symptomatic Progression
Time Frame	Participants were followed up every 4 weeks for the first 16 weeks then every 16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	ZD4054		Placebo
Arm/Group Description	ZD4054 10 mg oral tablet once daily		Placebo oral tablet once daily
All Cause Mortality
	ZD4054		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	ZD4054		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	148/703 (21.1%)		138/712 (19.4%)
Blood and lymphatic system disorders
Disseminated Intravascular Coagulation	2/703 (0.3%)		0/712 (0%)
Anaemia	1/703 (0.1%)		1/712 (0.1%)
Febrile Neutropenia	1/703 (0.1%)		0/712 (0%)
Hilar Lymphadenopathy	1/703 (0.1%)		0/712 (0%)
Iron Deficiency Anaemia	0/703 (0%)		1/712 (0.1%)
Lymphadenopathy	1/703 (0.1%)		0/712 (0%)
Neutropenia	1/703 (0.1%)		1/712 (0.1%)
Pancytopenia	0/703 (0%)		1/712 (0.1%)
Cardiac disorders
Cardiac Failure	9/703 (1.3%)		3/712 (0.4%)
Angina Pectoris	1/703 (0.1%)		7/712 (1%)
Myocardial Infarction	5/703 (0.7%)		3/712 (0.4%)
Atrial Fibrillation	4/703 (0.6%)		2/712 (0.3%)
Coronary Artery Disease	3/703 (0.4%)		0/712 (0%)
Acute Myocardial Infarction	2/703 (0.3%)		2/712 (0.3%)
Cardiac Arrest	0/703 (0%)		2/712 (0.3%)
Cardiac Failure Congestive	2/703 (0.3%)		1/712 (0.1%)
Cardio-Respiratory Arrest	0/703 (0%)		2/712 (0.3%)
Acute Coronary Syndrome	1/703 (0.1%)		0/712 (0%)
Angina Unstable	0/703 (0%)		1/712 (0.1%)
Atrial Flutter	1/703 (0.1%)		0/712 (0%)
Bradycardia	1/703 (0.1%)		1/712 (0.1%)
Cardiac Disorder	1/703 (0.1%)		0/712 (0%)
Cardiac Failure Acute	1/703 (0.1%)		0/712 (0%)
Cardiac Failure Chronic	0/703 (0%)		1/712 (0.1%)
Diastolic Dysfunction	1/703 (0.1%)		0/712 (0%)
Hypertensive Cardiomyopathy	1/703 (0.1%)		0/712 (0%)
Mitral Valve Incompetence	1/703 (0.1%)		1/712 (0.1%)
Prinzmetal Angina	0/703 (0%)		1/712 (0.1%)
Sinus Bradycardia	1/703 (0.1%)		0/712 (0%)
Ventricular Fibrillation	0/703 (0%)		1/712 (0.1%)
Congenital, familial and genetic disorders
Congenital Aortic Valve Stenosis	1/703 (0.1%)		0/712 (0%)
Phimosis	1/703 (0.1%)		0/712 (0%)
Ear and labyrinth disorders
Vertigo	2/703 (0.3%)		0/712 (0%)
Endocrine disorders
Hypothyroidism	1/703 (0.1%)		0/712 (0%)
Eye disorders
Cataract	2/703 (0.3%)		1/712 (0.1%)
Macular Hole	0/703 (0%)		1/712 (0.1%)
Gastrointestinal disorders
Abdominal Pain	2/703 (0.3%)		0/712 (0%)
Diarrhoea	2/703 (0.3%)		1/712 (0.1%)
Inguinal Hernia	2/703 (0.3%)		2/712 (0.3%)
Abdominal Hernia	1/703 (0.1%)		0/712 (0%)
Abdominal Pain Upper	0/703 (0%)		1/712 (0.1%)
Abdominal Wall Haematoma	0/703 (0%)		1/712 (0.1%)
Constipation	0/703 (0%)		1/712 (0.1%)
Duodenitis	1/703 (0.1%)		0/712 (0%)
Dyspepsia	0/703 (0%)		1/712 (0.1%)
Food Poisoning	0/703 (0%)		1/712 (0.1%)
Gastric Haemorrhage	1/703 (0.1%)		1/712 (0.1%)
Gastric Ulcer Haemorrhage	1/703 (0.1%)		0/712 (0%)
Gastritis	1/703 (0.1%)		1/712 (0.1%)
Gastritis Haemorrhagic	1/703 (0.1%)		0/712 (0%)
Intestinal Obstruction	1/703 (0.1%)		1/712 (0.1%)
Large Intestine Perforation	1/703 (0.1%)		0/712 (0%)
Mallory-Weiss Syndrome	1/703 (0.1%)		0/712 (0%)
Pancreatitis Acute	1/703 (0.1%)		0/712 (0%)
Peptic Ulcer Haemorrhage	0/703 (0%)		1/712 (0.1%)
Pneumatosis Intestinalis	0/703 (0%)		1/712 (0.1%)
Rectal Haemorrhage	0/703 (0%)		1/712 (0.1%)
Rectourethral Fistula	1/703 (0.1%)		0/712 (0%)
Small Intestinal Obstruction	0/703 (0%)		1/712 (0.1%)
Vomiting	0/703 (0%)		1/712 (0.1%)
General disorders
Oedema Peripheral	4/703 (0.6%)		0/712 (0%)
Death	2/703 (0.3%)		1/712 (0.1%)
Pyrexia	0/703 (0%)		2/712 (0.3%)
Asthenia	1/703 (0.1%)		1/712 (0.1%)
Chest Pain	1/703 (0.1%)		0/712 (0%)
Device Dislocation	0/703 (0%)		1/712 (0.1%)
General Physical Health Deterioration	1/703 (0.1%)		0/712 (0%)
Granuloma	0/703 (0%)		1/712 (0.1%)
Hypothermia	1/703 (0.1%)		0/712 (0%)
Impaired Healing	1/703 (0.1%)		0/712 (0%)
Malaise	0/703 (0%)		1/712 (0.1%)
Medical Device Complication	0/703 (0%)		1/712 (0.1%)
Multi-Organ Failure	0/703 (0%)		1/712 (0.1%)
Non-Cardiac Chest Pain	0/703 (0%)		1/712 (0.1%)
Hepatobiliary disorders
Bile Duct Stone	1/703 (0.1%)		1/712 (0.1%)
Cholecystitis Acute	1/703 (0.1%)		0/712 (0%)
Cholelithiasis	0/703 (0%)		1/712 (0.1%)
Hepatic Failure	0/703 (0%)		1/712 (0.1%)
Hepatic Function Abnormal	1/703 (0.1%)		1/712 (0.1%)
Liver Disorder	1/703 (0.1%)		0/712 (0%)
Infections and infestations
Pneumonia	7/703 (1%)		5/712 (0.7%)
Urinary Tract Infection	2/703 (0.3%)		3/712 (0.4%)
Bronchopneumonia	2/703 (0.3%)		0/712 (0%)
Lower Respiratory Tract Infection	2/703 (0.3%)		0/712 (0%)
Pyelonephritis	0/703 (0%)		2/712 (0.3%)
Upper Respiratory Tract Infection	2/703 (0.3%)		0/712 (0%)
Anal Abscess	1/703 (0.1%)		0/712 (0%)
Appendicitis	1/703 (0.1%)		0/712 (0%)
Cellulitis	1/703 (0.1%)		1/712 (0.1%)
Chronic Sinusitis	1/703 (0.1%)		0/712 (0%)
Cystitis	0/703 (0%)		1/712 (0.1%)
Diverticulitis	0/703 (0%)		1/712 (0.1%)
Lung Infection	0/703 (0%)		1/712 (0.1%)
Parainfluenzae Virus Infection	1/703 (0.1%)		0/712 (0%)
Pneumonia Bacterial	0/703 (0%)		1/712 (0.1%)
Pyelonephritis Acute	0/703 (0%)		1/712 (0.1%)
Respiratory Tract Infection	1/703 (0.1%)		1/712 (0.1%)
Scrotal Abscess	0/703 (0%)		1/712 (0.1%)
Septic Shock	0/703 (0%)		1/712 (0.1%)
Sinusitis	0/703 (0%)		1/712 (0.1%)
Staphylococcal Sepsis	0/703 (0%)		1/712 (0.1%)
Tooth Abscess	1/703 (0.1%)		0/712 (0%)
Urosepsis	0/703 (0%)		1/712 (0.1%)
Wound Infection	0/703 (0%)		1/712 (0.1%)
Injury, poisoning and procedural complications
Chest Injury	0/703 (0%)		2/712 (0.3%)
Rib Fracture	0/703 (0%)		2/712 (0.3%)
Subdural Haematoma	2/703 (0.3%)		1/712 (0.1%)
Cystitis Radiation	1/703 (0.1%)		1/712 (0.1%)
Fall	0/703 (0%)		1/712 (0.1%)
Femur Fracture	0/703 (0%)		1/712 (0.1%)
Gastroenteritis Radiation	1/703 (0.1%)		0/712 (0%)
Heat Illness	0/703 (0%)		1/712 (0.1%)
Hip Fracture	1/703 (0.1%)		1/712 (0.1%)
Injury	1/703 (0.1%)		0/712 (0%)
Open Fracture	0/703 (0%)		1/712 (0.1%)
Patella Fracture	0/703 (0%)		1/712 (0.1%)
Radiation Proctopathy	1/703 (0.1%)		0/712 (0%)
Spinal Compression Fracture	0/703 (0%)		1/712 (0.1%)
Thoracic Vertebral Fracture	0/703 (0%)		1/712 (0.1%)
Ulna Fracture	0/703 (0%)		1/712 (0.1%)
Upper Limb Fracture	1/703 (0.1%)		1/712 (0.1%)
Wrist Fracture	0/703 (0%)		1/712 (0.1%)
Haemoglobin Decreased	0/703 (0%)		1/712 (0.1%)
International Normalised Ratio Increased	0/703 (0%)		1/712 (0.1%)
Metabolism and nutrition disorders
Diabetes Mellitus	2/703 (0.3%)		2/712 (0.3%)
Diabetic Foot	1/703 (0.1%)		1/712 (0.1%)
Hyponatraemia	1/703 (0.1%)		0/712 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/703 (0.1%)		2/712 (0.3%)
Bone Pain	1/703 (0.1%)		0/712 (0%)
Intervertebral Disc Protrusion	1/703 (0.1%)		1/712 (0.1%)
Musculoskeletal Chest Pain	1/703 (0.1%)		0/712 (0%)
Musculoskeletal Pain	0/703 (0%)		1/712 (0.1%)
Osteoporotic Fracture	1/703 (0.1%)		0/712 (0%)
Spinal Column Stenosis	0/703 (0%)		1/712 (0.1%)
Systemic Lupus Erythematosus	0/703 (0%)		1/712 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric Cancer	2/703 (0.3%)		5/712 (0.7%)
Basal Cell Carcinoma	4/703 (0.6%)		1/712 (0.1%)
Colon Cancer	1/703 (0.1%)		3/712 (0.4%)
Rectal Cancer	0/703 (0%)		2/712 (0.3%)
Benign Urinary Tract Neoplasm	1/703 (0.1%)		0/712 (0%)
Bladder Cancer	1/703 (0.1%)		1/712 (0.1%)
Bladder Transitional Cell Carcinoma	1/703 (0.1%)		0/712 (0%)
Bladder Transitional Cell Carcinoma Recurrent	0/703 (0%)		1/712 (0.1%)
Colorectal Cancer	1/703 (0.1%)		0/712 (0%)
Gastrointestinal Tract Adenoma	1/703 (0.1%)		0/712 (0%)
Glioblastoma	0/703 (0%)		1/712 (0.1%)
Hepatic Neoplasm Malignant	0/703 (0%)		1/712 (0.1%)
Lung Neoplasm Malignant	0/703 (0%)		1/712 (0.1%)
Malignant Melanoma	0/703 (0%)		1/712 (0.1%)
Myelodysplastic Syndrome	1/703 (0.1%)		0/712 (0%)
Neuroendocrine Carcinoma	1/703 (0.1%)		0/712 (0%)
Pancreatic Carcinoma	1/703 (0.1%)		0/712 (0%)
Pancreatic Carcinoma Metastatic	1/703 (0.1%)		0/712 (0%)
Porocarcinoma	0/703 (0%)		1/712 (0.1%)
Renal Neoplasm	1/703 (0.1%)		0/712 (0%)
Small Cell Lung Cancer Stage Unspecified	1/703 (0.1%)		0/712 (0%)
Transitional Cell Carcinoma	1/703 (0.1%)		0/712 (0%)
Nervous system disorders
Cerebrovascular Accident	2/703 (0.3%)		1/712 (0.1%)
Dizziness	2/703 (0.3%)		1/712 (0.1%)
Ischaemic Stroke	1/703 (0.1%)		2/712 (0.3%)
Syncope	2/703 (0.3%)		0/712 (0%)
Transient Ischaemic Attack	2/703 (0.3%)		1/712 (0.1%)
Brain Stem Stroke	1/703 (0.1%)		0/712 (0%)
Cerebellar Haemorrhage	0/703 (0%)		1/712 (0.1%)
Cerebral Haemorrhage	1/703 (0.1%)		0/712 (0%)
Cerebral Infarction	0/703 (0%)		1/712 (0.1%)
Cerebral Ischaemia	1/703 (0.1%)		1/712 (0.1%)
Cerebrovascular Disorder	0/703 (0%)		1/712 (0.1%)
Cerebrovascular Insufficiency	1/703 (0.1%)		0/712 (0%)
Leukoencephalopathy	1/703 (0.1%)		0/712 (0%)
Parkinsonism	1/703 (0.1%)		0/712 (0%)
Subarachnoid Haemorrhage	0/703 (0%)		1/712 (0.1%)
Psychiatric disorders
Completed Suicide	1/703 (0.1%)		0/712 (0%)
Delirium	1/703 (0.1%)		0/712 (0%)
Suicidal Ideation	0/703 (0%)		1/712 (0.1%)
Renal and urinary disorders
Hydronephrosis	1/703 (0.1%)		7/712 (1%)
Renal Failure Acute	5/703 (0.7%)		2/712 (0.3%)
Calculus Ureteric	3/703 (0.4%)		0/712 (0%)
Renal Failure	2/703 (0.3%)		3/712 (0.4%)
Urinary Tract Obstruction	1/703 (0.1%)		3/712 (0.4%)
Haematuria	1/703 (0.1%)		2/712 (0.3%)
Renal Impairment	2/703 (0.3%)		0/712 (0%)
Urinary Retention	2/703 (0.3%)		1/712 (0.1%)
Azotaemia	1/703 (0.1%)		0/712 (0%)
Bladder Stenosis	0/703 (0%)		1/712 (0.1%)
Calculus Bladder	1/703 (0.1%)		0/712 (0%)
Calculus Urinary	1/703 (0.1%)		0/712 (0%)
Cystitis Haemorrhagic	0/703 (0%)		1/712 (0.1%)
Renal Disorder	1/703 (0.1%)		0/712 (0%)
Urethral Stenosis	1/703 (0.1%)		0/712 (0%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	0/703 (0%)		1/712 (0.1%)
Calculus Prostatic	1/703 (0.1%)		0/712 (0%)
Pelvic Haematoma	1/703 (0.1%)		0/712 (0%)
Prostatic Haemorrhage	0/703 (0%)		1/712 (0.1%)
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism	3/703 (0.4%)		4/712 (0.6%)
Chronic Obstructive Pulmonary Disease	3/703 (0.4%)		0/712 (0%)
Dyspnoea	3/703 (0.4%)		0/712 (0%)
Emphysema	2/703 (0.3%)		0/712 (0%)
Pleural Effusion	2/703 (0.3%)		0/712 (0%)
Asthma	1/703 (0.1%)		0/712 (0%)
Epistaxis	0/703 (0%)		1/712 (0.1%)
Lung Consolidation	1/703 (0.1%)		0/712 (0%)
Pneumonia Aspiration	1/703 (0.1%)		0/712 (0%)
Pneumothorax	0/703 (0%)		1/712 (0.1%)
Pulmonary Hypertension	1/703 (0.1%)		0/712 (0%)
Pulmonary Infarction	0/703 (0%)		1/712 (0.1%)
Sleep Apnoea Syndrome	1/703 (0.1%)		0/712 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/703 (0.1%)		0/712 (0%)
Peau D'orange	0/703 (0%)		1/712 (0.1%)
Vascular disorders
Deep Vein Thrombosis	2/703 (0.3%)		3/712 (0.4%)
Aortic Aneurysm	0/703 (0%)		1/712 (0.1%)
Arterial Stenosis	0/703 (0%)		1/712 (0.1%)
Arteritis	0/703 (0%)		1/712 (0.1%)
Femoral Arterial Stenosis	1/703 (0.1%)		0/712 (0%)
Iliac Artery Occlusion	0/703 (0%)		1/712 (0.1%)
Intermittent Claudication	0/703 (0%)		1/712 (0.1%)
Temporal Arteritis	0/703 (0%)		1/712 (0.1%)
Thrombosis	0/703 (0%)		1/712 (0.1%)
twqVenous Thrombosis	0/703 (0%)		1/712 (0.1%)
Other (Not Including Serious) Adverse Events
	ZD4054		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	531/703 (75.5%)		392/712 (55.1%)
Blood and lymphatic system disorders
Anaemia	46/703 (6.5%)		23/712 (3.2%)
Gastrointestinal disorders
Constipation	64/703 (9.1%)		76/712 (10.7%)
Diarrhoea	46/703 (6.5%)		63/712 (8.8%)
Nausea	59/703 (8.4%)		61/712 (8.6%)
General disorders
Oedema Peripheral	268/703 (38.1%)		88/712 (12.4%)
Fatigue	71/703 (10.1%)		79/712 (11.1%)
Asthenia	35/703 (5%)		43/712 (6%)
Infections and infestations
Rhinitis	56/703 (8%)		17/712 (2.4%)
Urinary Tract Infection	43/703 (6.1%)		54/712 (7.6%)
Nasopharyngitis	34/703 (4.8%)		45/712 (6.3%)
Metabolism and nutrition disorders
Decreased Appetite	40/703 (5.7%)		33/712 (4.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	40/703 (5.7%)		54/712 (7.6%)
Back Pain	33/703 (4.7%)		49/712 (6.9%)
Nervous system disorders
Headache	188/703 (26.7%)		82/712 (11.5%)
Dizziness	46/703 (6.5%)		39/712 (5.5%)
Renal and urinary disorders
Haematuria	23/703 (3.3%)		36/712 (5.1%)
Respiratory, thoracic and mediastinal disorders
Nasal Congestion	176/703 (25%)		39/712 (5.5%)
Dyspnoea	49/703 (7%)		33/712 (4.6%)
Nasal Obstruction	48/703 (6.8%)		4/712 (0.6%)
Cough	36/703 (5.1%)		34/712 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

3. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. AstraZeneca can review results communications prior to public release and may within 60 days of receipt require amendments to be made. AstraZeneca can also require that submission or disclosure be delayed to allow for