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
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     ZD4054 22.5 mg  
STARTED     3 [1]   6 [2]   0  
COMPLETED     3     6     0  
NOT COMPLETED     0     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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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

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. ]

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

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

4.  Secondary:   Change in Serum Concentration of Bone Alkaline Phosphatase (ALP)   [ Time Frame: Baseline to Day 15. ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Change in Serum Concentration of Bone Alkaline Phosphatase (ALP)
Measure Description Percentage change in serum concentration of Bone Alkaline Phosphatase (ALP) (ng/mL) from baseline to Day 15 (14 doses of study treatment per patient – no dose was administered on Day 2). Percentage change = [(measure at Day 15 – measure at baseline)/measure at baseline]*100
Time Frame Baseline to Day 15.  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis population includes only patients dosed with ZD4054

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

Measured Values
    ZD4054 10 mg     ZD4054 15 mg     ZD4054 22.5 mg  
Number of Participants Analyzed  
[units: participants]
  3     10     2  
Change in Serum Concentration of Bone Alkaline Phosphatase (ALP)  
[units: Percentage¬†Change]
Mean ± Standard Deviation
  -6.161  ± 9.616     -9.197  ± 12.220     -9.182  ± 10.644  

No statistical analysis provided for Change in Serum Concentration of Bone Alkaline Phosphatase (ALP)



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

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

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


  Serious Adverse Events


  Other Adverse Events


  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:
unchecked 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.
unchecked 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