A Phase IIa. Open-label, Multicenter, Dose-escalation Study to Assess the Tolerability and Pharmacokinetics of ZD4054 (Zibotentan) Given Orally Once Daily in Subjects With Metastatic Prostate Cancer

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

AstraZeneca

ClinicalTrials.gov Identifier:

NCT00055471

First received: March 3, 2003

Last updated: October 23, 2012

Last verified: October 2012

History of Changes

Results First Received: March 29, 2011

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Conditions:	Prostatic Neoplasms Metastases, Neoplasm
Interventions:	Drug: ZD4054 10 mg Drug: ZD4054 15 mg Drug: ZD4054 22.5 mg

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
22 male patients with metastatic prostate cancer and rising Prostate Specific Antigen (PSA) levels were recruited from 11th June 2003 (last subject completed on 31st October 2005). This study was conducted in 2 centres in the United States.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
6 of the 22 screened patients were not entered into the study as they did not fulfill the study eligibility criteria.

Reporting Groups

	Description
ZD4054 10 mg	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily
ZD4054 15 mg	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily
ZD4054 22.5 mg	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily

Participant Flow for 2 periods

Period 1: Period 1: Dose Escalation Period

	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
STARTED	3	10 ^[1]	3 ^[1]
COMPLETED	3	8	0
NOT COMPLETED	0	2	3
Adverse Event	0	1	2
Erroneously reported discont. criteria	0	0	1
Disease progression	0	1	0

[1]	Dose level given only after lower dose was successfully administered.

Period 2: Period 2: Extension Period

	ZD4054 10 mg	ZD4054 15 mg
STARTED	3 ^[1]	6 ^[2]
COMPLETED	3	6
NOT COMPLETED	0	0

[1]	Period 2 - attend Pts who,in the opinion of the Investigator,show benefit from treatment with ZD4054
[2]	2 pts discontinued after completion of Period1,therefore 9 pts proceeded to participate in Period2

Baseline Characteristics

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Reporting Groups

	Description
ZD4054 10 mg	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily
ZD4054 15 mg	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily
ZD4054 22.5 mg	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily
Total	Total of all reporting groups

Baseline Measures

	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg	Total
Number of Participants [units: participants]	3	10	3	16
Age [units: Years] Mean ± Standard Deviation
Overall	72.3 ± 3.21	64.6 ± 9.72	66.3 ± 8.08	66.4 ± 8.72
Gender [units: Participants]
Female	0	0	0	0
Male	3	10	3	16
Race/Ethnicity, Customized [units: Participants]
Caucasian	3	9	3	15
Black	0	1	0	1
Oriental	0	0	0	0
Other	0	0	0	0
Height [units: Centimeters (cm)] Mean ± Standard Deviation	177.33 ± 4.51	177.10 ± 8.02	176.33 ± 5.03	177 ± 6.69
Weight [units: Kilograms (kg)] Mean ± Standard Deviation	87.33 ± 19.035	107.8 ± 21.060	103.00 ± 35.595	103.06 ± 23.405

Outcome Measures

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1. Primary:

Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline to Day 29. ]

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2. Secondary:

Total Prostate Specific Antigen (PSA) Concentration [ Time Frame: Baseline to Day 15. ]

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3. Secondary:

Change in Total Prostate Specific Antigen (PSA) [ Time Frame: Baseline to Day 15. ]

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4. Secondary:

Change in Serum Concentration of Bone Alkaline Phosphatase (ALP) [ Time Frame: Baseline to Day 15. ]

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5. Secondary:

Change in Serum Concentration of Procollagen Type I N Propeptide (PINP) [ Time Frame: Baseline to Day 15. ]

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6. Secondary:

Change in Serum Concentration of C-Terminal Telopeptide of Type I Collagen (CTx) [ Time Frame: Baseline to Day 15. ]

Show Outcome Measure 6

7. Secondary:

Change in Urine Concentration of Type I Collagen-Cross Linked N Telopeptide (NTx) [ Time Frame: Baseline to Day 15. ]

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Serious Adverse Events

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Other Adverse Events

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Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
ZD4054 10 mg	ZD4054 10 mg dose: 1 x 10 mg oral tablet once daily
ZD4054 15 mg	ZD4054 15 mg dose: 1 x 10 mg + 2 x 2.5 mg oral tablets once daily
ZD4054 22.5 mg	ZD4054 22.5 mg dose: 2 x 10 mg + 1 x 2.5 mg oral tablets once daily

Other Adverse Events

	ZD4054 10 mg	ZD4054 15 mg	ZD4054 22.5 mg
Total, other (not including serious) adverse events
# participants affected / at risk	3/3	10/10	3/3
Blood and lymphatic system disorders
Anaemia ^{† 1}
# participants affected / at risk	1/3 (33.33%)	0/10 (0.00%)	0/3 (0.00%)
Cardiac disorders
Tachycardia ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Ear and labyrinth disorders
Tinnitus ^{† 1}
# participants affected / at risk	1/3 (33.33%)	0/10 (0.00%)	0/3 (0.00%)
Ear Discomfort ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Eye disorders
Cataract ^{† 1}
# participants affected / at risk	1/3 (33.33%)	0/10 (0.00%)	0/3 (0.00%)
Lacrimation Increased ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Photophobia ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Gastrointestinal disorders
Constipation ^{† 1}
# participants affected / at risk	1/3 (33.33%)	0/10 (0.00%)	0/3 (0.00%)
Nausea ^{† 1}
# participants affected / at risk	1/3 (33.33%)	2/10 (20.00%)	1/3 (33.33%)
Vomiting ^{† 1}
# participants affected / at risk	1/3 (33.33%)	1/10 (10.00%)	1/3 (33.33%)
Abdominal Distension ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Abdominal Pain ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Diarrhoea ^{† 1}
# participants affected / at risk	0/3 (0.00%)	3/10 (30.00%)	0/3 (0.00%)
Dry Mouth ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Flatulence ^{† 1}
# participants affected / at risk	0/3 (0.00%)	2/10 (20.00%)	0/3 (0.00%)
Stomatitis ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Tongue Discolouration ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
General disorders
Fatigue ^{† 1}
# participants affected / at risk	0/3 (0.00%)	4/10 (40.00%)	3/3 (100.00%)
Oedema Peripheral ^{† 1}
# participants affected / at risk	0/3 (0.00%)	9/10 (90.00%)	1/3 (33.33%)
Chills ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	1/3 (33.33%)
Oedema ^{† 1}
# participants affected / at risk	1/3 (33.33%)	0/10 (0.00%)	0/3 (0.00%)
Face Oedema ^{† 1}
# participants affected / at risk	0/3 (0.00%)	3/10 (30.00%)	0/3 (0.00%)
Infections and infestations
Bronchitis ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Nasopharyngitis ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Rhinitis ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Injury, poisoning and procedural complications
Animal Bite ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Arthropod Sting ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Barotrauma ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Contrast Media Reaction ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Joint Sprain ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Scratch ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Weight Increased ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	1/3 (33.33%)
Weight Decreased ^{† 1}
# participants affected / at risk	1/3 (33.33%)	1/10 (10.00%)	0/3 (0.00%)
Electrocardiogram Qt Corrected Interval Prolonged ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Haemoglobin Decreased ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Heart Rate Increased ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Metabolism and nutrition disorders
Anorexia ^{† 1}
# participants affected / at risk	0/3 (0.00%)	2/10 (20.00%)	1/3 (33.33%)
Musculoskeletal and connective tissue disorders
Arthralgia ^{† 1}
# participants affected / at risk	1/3 (33.33%)	2/10 (20.00%)	2/3 (66.67%)
Back Pain ^{† 1}
# participants affected / at risk	1/3 (33.33%)	1/10 (10.00%)	0/3 (0.00%)
Pain In Extremity ^{† 1}
# participants affected / at risk	1/3 (33.33%)	1/10 (10.00%)	2/3 (66.67%)
Buttock Pain ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Groin Pain ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Nervous system disorders
Headache ^{† 1}
# participants affected / at risk	2/3 (66.67%)	9/10 (90.00%)	3/3 (100.00%)
Dizziness ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	1/3 (33.33%)
Burning Sensation ^{† 1}
# participants affected / at risk	1/3 (33.33%)	0/10 (0.00%)	0/3 (0.00%)
Dysgeusia ^{† 1}
# participants affected / at risk	0/3 (0.00%)	2/10 (20.00%)	0/3 (0.00%)
Hypoaesthesia ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Neuropathy ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Paraesthesia ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Psychiatric disorders
Insomnia ^{† 1}
# participants affected / at risk	1/3 (33.33%)	0/10 (0.00%)	0/3 (0.00%)
Renal and urinary disorders
Haematuria ^{† 1}
# participants affected / at risk	0/3 (0.00%)	2/10 (20.00%)	0/3 (0.00%)
Urinary Retention ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Reproductive system and breast disorders
Testicular Pain ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Respiratory, thoracic and mediastinal disorders
Sinus Congestion ^{† 1}
# participants affected / at risk	0/3 (0.00%)	2/10 (20.00%)	2/3 (66.67%)
Dyspnoea ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	1/3 (33.33%)
Nasal Congestion ^{† 1}
# participants affected / at risk	1/3 (33.33%)	3/10 (30.00%)	0/3 (0.00%)
Dry Throat ^{† 1}
# participants affected / at risk	0/3 (0.00%)	2/10 (20.00%)	0/3 (0.00%)
Dyspnoea Exertional ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Pharyngolaryngeal Pain ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Postnasal Drip ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Rhinorrhoea ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Wheezing ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Skin and subcutaneous tissue disorders
Pruritus ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	1/3 (33.33%)
Hyperhidrosis ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)
Periorbital Oedema ^{† 1}
# participants affected / at risk	0/3 (0.00%)	2/10 (20.00%)	0/3 (0.00%)
Skin Discolouration ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Vascular disorders
Flushing ^{† 1}
# participants affected / at risk	0/3 (0.00%)	1/10 (10.00%)	0/3 (0.00%)
Hypotension ^{† 1}
# participants affected / at risk	0/3 (0.00%)	0/10 (0.00%)	1/3 (33.33%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 9.0

More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
One patient received one dose of 22.5 mg and was dose reduced to 15 mg thereafter. This patient was classified into the 15 mg dose group, except for the single dose pharmacokinetic results (not posted).

Results Point of Contact:

Name/Title: Gerard Lynch
Organization: AstraZeneca
e-mail: aztrial_results_posting@astrazeneca.com

No publications provided

Responsible Party:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00055471 History of Changes
Other Study ID Numbers:	4054IL/0004
Study First Received:	March 3, 2003
Results First Received:	March 29, 2011
Last Updated:	October 23, 2012
Health Authority:	United States: Food and Drug Administration

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