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
  Hide Participant Flow

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
  Hide Baseline Characteristics

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  
Number of Participants  
[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  
Gender [2]
[units: participants]
         
Female     0     0     0     0     0  
Male     125     126     69     65     385  
Region of Enrollment [2]
[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  
Body Weight [2]
[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  
Body Mass Index [2]
[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  
Gleason Score [3]
[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  
Stage of Prostate Cancer [4]
[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  
Serum Testosterone Levels [2]
[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 )  
Serum Prostate-Specific Antigen (PSA) Levels [2]
[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 intention-to-treat (ITT) population.
[2] CS21A ITT population.
[3] 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.
[4] 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.



  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
No text entered.


  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


No publications provided


Responsible Party: Ferring Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00451958     History of Changes
Other Study ID Numbers: FE200486 CS21A, 2006-006913-34
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