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A Long-term Extension Study Evaluating a One-Month Dosing Regimen of Degarelix in Prostate Cancer Requiring Androgen Ablation Therapy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ferring Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00451958
First received: March 23, 2007
Last updated: March 20, 2013
Last verified: March 2013
Results First Received: October 10, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Prostate Cancer
Interventions: Drug: Degarelix 80 mg / Degarelix 80 mg
Drug: Degarelix 160 mg / Degarelix 160 mg
Drug: Leuprolide 7.5 mg / Degarelix 80 mg
Drug: Leuprolide 7.5 mg / Degarelix 160 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
All participants who completed the CS21 study (NCT00295750) were eligible to enrol into the CS21A extension study. Since the number of participants who completed this long-term study was low, no firm conclusions can be drawn from the results.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Initially, participants treated with degarelix during CS21 continued to treatment and patients who received treatment with leuprolide during CS21 were re-randomised to one of the two degarelix treatment regimens. Following a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg for the rest of the study.

Reporting Groups
  Description
Degarelix 80 mg / Degarelix 80 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 of the CS21 study (NCT00295750) as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the CS21 study and the current CS21A study.
Degarelix 160 mg / Degarelix 160 mg

The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 of the CS21 study (NCT00295750) as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the CS21 study and the current CS21A study.

Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.

Leuprolide 7.5 mg / Degarelix 80 mg

During the main CS21 study (NCT00295750), leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year.

Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study.

Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.

Leuprolide 7.5 mg / Degarelix 160 mg

During the main CS21 study (NCT00295750), leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year.

Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study.

Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.

Leuprolide 7.5 mg

During the main CS21 study (NCT00295750), leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year.

When the main CS21 study was completed these patients were switched to treatment with degarelix 80 mg or 160 mg in the CS21A study.


Participant Flow for 2 periods

Period 1:   CS21 (NCT00295750)
    Degarelix 80 mg / Degarelix 80 mg   Degarelix 160 mg / Degarelix 160 mg   Leuprolide 7.5 mg / Degarelix 80 mg   Leuprolide 7.5 mg / Degarelix 160 mg   Leuprolide 7.5 mg
STARTED   210 [1]   206 [2]   0 [3]   0 [3]   204 
COMPLETED   169   163   0   0   172 
NOT COMPLETED   41   43   0   0   32 
[1] CS21 intention-to-treat (ITT) population.
[2] CS21 ITT population.
[3] Participants were switched from the leuprolide 7.5 mg group when CS21 was completed.

Period 2:   CS21A (NCT00451958)
    Degarelix 80 mg / Degarelix 80 mg   Degarelix 160 mg / Degarelix 160 mg   Leuprolide 7.5 mg / Degarelix 80 mg   Leuprolide 7.5 mg / Degarelix 160 mg   Leuprolide 7.5 mg
STARTED   125 [1]   126 [2]   69 [2]   66 [3]   0 [4] 
COMPLETED   60   49   27   27   0 
NOT COMPLETED   65   77   42   39   0 
Adverse Event                21                34                14                17                0 
Lost to Follow-up                6                5                1                1                0 
Protocol Violation                1                3                2                0                0 
Physician Decision                2                4                4                4                0 
Withdrawal by Subject                7                4                4                3                0 
Miscellaneous reasons                28                27                17                14                0 
[1] CS21A intention-to-treat (ITT) population.
[2] CS21A ITT population.
[3] One of the enrolled participants never received any treatment, i.e. the CS21A ITT population=65.
[4] Participants were switched to the degarelix groups when CS21 was completed.



  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.
CS21A intention-to-treat (ITT) population.

Reporting Groups
  Description
Degarelix 80 mg / Degarelix 80 mg The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent doses of 80 mg (20 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days for the rest of the study.
Degarelix 160 mg / Degarelix 160 mg

The degarelix doses were administered into the abdominal wall every 28 days. A starting dose of 240 mg (40 mg/mL) degarelix was administered on Day 0 as two 3 mL subcutaneous (s.c.) injections. The subsequent monthly degarelix maintenance dose of 160 mg (40 mg/mL) degarelix were administered as single 4 mL s.c. injections every 28 days.

Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.

Leuprolide 7.5 mg / Degarelix 80 mg

During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year.

Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study.

Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.

Leuprolide 7.5 mg / Degarelix 160 mg

During the main CS21 study, leuprolide (Lupron Depot) 7.5 mg was injected into the muscle every 28 days for one year.

Starting one year after the first dose of leuprolide, degarelix doses were administered into the abdominal wall every 28 days. First, a starting dose of 240 mg (40 mg/mL) degarelix was administered as two 3 mL subcutaneous (s.c.) injections and one month later the participants received either subsequent monthly degarelix maintenance doses of 80 mg (20 mg/mL) or 160 mg (40 mg/mL) every 28 days for the rest of the study.

Following the implementation of a protocol amendment, all patients received a monthly degarelix maintenance dose of 80 mg (20 mg/mL) for the rest of the study.

Total Total of all reporting groups

Baseline Measures
   Degarelix 80 mg / Degarelix 80 mg   Degarelix 160 mg / Degarelix 160 mg   Leuprolide 7.5 mg / Degarelix 80 mg   Leuprolide 7.5 mg / Degarelix 160 mg   Total 
Overall Participants Analyzed 
[Units: Participants]
 125   126   69   65   385 
Age [1] 
[Units: Years]
Mean (Standard Deviation)
 70.1  (7.62)   71.1  (8.25)   72.4  (9.46)   71.4  (8.24)   71.1  (8.29) 
[1] CS21A intention-to-treat (ITT) population.
Gender [1] 
[Units: Participants]
         
Female   0   0   0   0   0 
Male   125   126   69   65   385 
[1] CS21A ITT population.
Region of Enrollment [1] 
[Units: Participants]
         
United States   12   14   13   9   48 
Hungary   7   9   5   5   26 
Czech Republic   11   12   6   8   37 
Mexico   15   17   10   7   49 
Canada   4   5   5   4   18 
Ukraine   11   10   7   3   31 
Romania   36   39   16   15   106 
Russian Federation   26   19   6   13   64 
Netherlands   2   0   0   1   3 
Germany   0   0   1   0   1 
United Kingdom   1   1   0   0   2 
[1] CS21A ITT population.
Body Weight [1] 
[Units: Kilogram]
Mean (Standard Deviation)
 78.4  (12.6)   79.2  (13.4)   78.7  (11.3)   80.0  (12.1)   79.0  (12.5) 
[1] CS21A ITT population.
Body Mass Index [1] 
[Units: Kilogram per square meter]
Mean (Standard Deviation)
 26.4  (3.92)   26.9  (3.79)   26.9  (3.94)   27.1  (3.67)   26.8  (3.84) 
[1] CS21A ITT population.
Gleason Score [1] 
[Units: Participants]
         
Gleason Score 2-4   15   17   8   11   51 
Gleason Score 5-6   37   44   25   18   124 
Gleason Score 7-10   73   63   36   36   208 
[1] CS21A ITT population. The Gleason Score is a system of grading the aggressiveness of the prostate cancer and how fast it is likely to grow and spread. Scale is 2-10, with low numbers being the least aggressive and 10 being the most aggressive. Two of the participants did not have a Gleason Score at Baseline.
Stage of Prostate Cancer [1] 
[Units: Participants]
         
Localised   39   36   20   19   114 
Locally advanced   46   44   18   24   132 
Metastatic   23   22   21   9   75 
Not classifiable   17   24   10   13   64 
[1] CS21A ITT population. Prostate cancer stage was classified according to the Tumor, Nodes, and Metastatic (TNM) scale to describe the extent of cancer. Localized refers to tumors without involvement of lymph nodes or metastasis. Advanced localized can be larger tumors that may involve the lymph nodes but no metastasis. Metastatic are more advanced cancers that are spreading beyond the original tumor.
Serum Testosterone Levels [1] 
[Units: Nanograms per milliliter]
Median (Full Range)
 4.63 
 (1.28 to 10.6) 
 4.02 
 (0.55 to 10.6) 
 4.32 
 (1.34 to 12.5) 
 3.51 
 (0.37 to 8.00) 
 4.23 
 (0.37 to 12.5) 
[1] CS21A ITT population.
Serum Prostate-Specific Antigen (PSA) Levels [1] 
[Units: Nanograms per milliliter]
Median (Full Range)
 22.2 
 (1.70 to 3187) 
 22.5 
 (1.50 to 4902) 
 25.5 
 (1.60 to 2112) 
 14.0 
 (1.60 to 10952) 
 21.0 
 (1.50 to 10952) 
[1] CS21A ITT population.


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Markedly Abnormal Values in Vital Signs and Body Weight   [ Time Frame: Up to 4 years of treatment ]

2.  Primary:   Number of Participants With Markedly Abnormal Values in Safety Laboratory Variables   [ Time Frame: Up to 4 years of treatment ]

3.  Secondary:   Percentage of Participants With no Prostate-specific Antigen (PSA) Progression   [ Time Frame: Until all participants have received at least 5 years of treatment and at a frequency of every 3 months ]

4.  Secondary:   Percentage of Participants With Testosterone Level Maintained at <=0.5 ng/mL From Day 28 in CS21 and Onwards   [ Time Frame: Until all participants have received at least 5 years of treatment and at a frequency of every 6 months ]

5.  Secondary:   Serum Levels of Testosterone From the Time of Switch From Leuprolide to Degarelix up to Day 56   [ Time Frame: From time of switch to Day 56 ]

6.  Secondary:   Serum Levels of PSA From the Time of Switch From Leuprolide to Degarelix to Day 56   [ Time Frame: From time of switch to Day 56 ]

7.  Secondary:   Serum Levels of Luteinizing Hormone (LH) From the Time of Switch From Leuprolide to Degarelix to Day 56   [ Time Frame: From time of switch to Day 56 ]

8.  Secondary:   Serum Levels of Follicle Stimulating Hormone (FSH) From the Time of Switch From Leuprolide to Degarelix to Day 56   [ Time Frame: From time of switch to Day 56 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  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 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.


Results Point of Contact:  
Name/Title: Clinical Development Support
Organization: Ferring Pharmaceuticals
e-mail: DK0-Disclosure@ferring.com



Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00451958     History of Changes
Other Study ID Numbers: FE200486 CS21A
2006-006913-34 ( EudraCT Number )
Study First Received: March 23, 2007
Results First Received: October 10, 2012
Last Updated: March 20, 2013
Health Authority: United States: Food and Drug Administration