A Trial of Degarelix in Patients With Prostate Cancer - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Prostate Cancer
Interventions:	Drug: Degarelix Drug: Goserelin acetate

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects who met the eligibility criteria were randomized to degarelix or goserelin acetate treatment in a 2:1-ratio. 859 subjects were randomized but 11 subjects did not receive any treatment.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Degarelix 240 mg/480 mg	Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).
Goserelin Acetate	Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).

Participant Flow: Overall Study

	Degarelix 240 mg/480 mg	Goserelin Acetate
STARTED	565 ^[1]	283 ^[2]
Full Analysis Set (FAS)	565 ^[3]	282 ^[4]
COMPLETED	455	239
NOT COMPLETED	110	44
Withdrawal by Subject	28	15
Lost to Follow-up	2	2
Physician Decision	5	2
Adverse Event	41	14
Protocol Violation	16	8
Miscellaneous reasons	18	3

^[1]	Received at least one dose of degarelix.
^[2]	Received at least one dose of goserelin acetate.
^[3]	Received at least one dose of degarelix and had at least one post-dosing efficacy assessment.
^[4]	Received at least one dose of goserelin and had at least one post-dosing efficacy assessment.

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.
FAS

Reporting Groups

	Description
Degarelix 240 mg/480 mg	Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).
Goserelin Acetate	Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).
Total	Total of all reporting groups

Baseline Measures

Degarelix 240 mg/480 mg

Goserelin Acetate

Total

Overall Participants Analyzed
[Units: Participants]

565

282

847

Age
[Units: Years]
Mean (Standard Deviation)

71.9 (8.3)

71.1 (7.9)

71.6 (8.2)

Gender
[Units: Participants]

Female

0

Male

565

282

847

Race (NIH/OMB)
[Units: Participants]

American Indian or Alaska Native

45

25

70

Asian

4

1

5

Native Hawaiian or Other Pacific Islander

0

1

Black or African American

41

16

57

White

475

239

714

More than one race

0

Unknown or Not Reported

0

Median Baseline Serum Testosterone Levels (ng/mL)
[Units: ng/mL]
Median (Full Range)

4.52
(0.56 to 14.5)

4.62
(0.07 to 13.2)

4.54
(0.07 to 14.5)

Median Baseline Serum Prostate-specific Antigen Levels (ng/mL)
[Units: ng/mL]
Median (Full Range)

19.0
(0.26 to 8762)

19.1
(0.01 to 12961)

19.0
(0.01 to 12961)

Baseline Short Form-36 (SF-36) Total Scores ^[1]
[Units: Units on a scale]
Mean (Standard Deviation)

49.7 (11.5)

50.2 (11.4)

49.9 (11.4)

^[1]

The SF-36 is a multi-purpose, short-form health survey with only 36 questions and with a minimum score of 0 and a maximum score of 100. The higher score the better health. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. The SF-36 has proven useful in surveys of general and specific populations, comparing the relative burden of diseases, and in differentiating the health benefits produced by a wide range of different treatments.

Baseline Total International Prostate Symptom Scores (IPSS) ^[1]
[Units: Units on a scale]
Mean (Standard Deviation)

11.8 (7.93)

11.6 (8.02)

11.7 (7.96)

^[1]

IPSS is used to assess severity of lower urinary tract symptoms and to monitor the progress of symptoms once treatment has been initiated. It contains 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5 (i.e. the minimum total score is 0 and the maximum is 35). A score of “0” corresponds to a response of “not at all” for the first six symptoms and “none” for nocturia, and a score of 5 corresponds to a response of “almost always” for the first six symptoms and “5 times or more” for nocturia.

Outcome Measures

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1. Primary:

Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) With Degarelix [ Time Frame: From Day 28 to Day 364 ]

Measure Type	Primary
Measure Title	Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) With Degarelix
Measure Description	This co-primary outcome measure was used to demonstrate that degarelix is effective with respect to achieving and maintaining testosterone suppression to castrate levels, evaluated as the proportion of patients with testosterone suppression ≤0.5 ng/mL from Day 28 to Day 364.
Time Frame	From Day 28 to Day 364

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.
FAS.

Reporting Groups

	Description
Degarelix 240 mg/480 mg	Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).

Measured Values

	Degarelix 240 mg/480 mg
Participants Analyzed [Units: Participants]	565
Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) With Degarelix [Units: Percentage of participants] Number (95% Confidence Interval)	90.0 (87.0 to 92.3)

No statistical analysis provided for Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) With Degarelix

2. Primary:

Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin [ Time Frame: Day 3 to Day 364 ]

Measure Type	Primary
Measure Title	Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin
Measure Description	This co-primary outcome measure was used to establish non-inferiority of degarelix as compared to goserelin with regard to achieving and maintaining testosterone suppression at castrate levels (≤0.5 ng/mL) from Day 3 to Day 364, using a non-inferiority margin of 5 percentage points.
Time Frame	Day 3 to Day 364

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.
FAS.

Reporting Groups

	Description
Degarelix 240 mg/480 mg	Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).
Goserelin Acetate	Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).

Measured Values

	Degarelix 240 mg/480 mg	Goserelin Acetate
Participants Analyzed [Units: Participants]	565	282
Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin [Units: Percentage of participants] Number (95% Confidence Interval)	85.0 (81.6 to 87.8)	5.3 (3.1 to 8.4)

Statistical Analysis 1 for Difference in Cumulative Probability of Testosterone at Castrate Level (≤0.5 ng/mL) Between Degarelix and Goserelin

Groups ^[1]	All groups
Statistical Test Type ^[2]	Non-Inferiority or Equivalence
Kaplan-Meier estimate ^[3]	79.6
95% Confidence Interval	75.6 to 83.7

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	The cumulative probability of testosterone ≤0.5 ng/mL from Day 3 to Day 364 was estimated by the Kaplan-Meier method. Only testosterone measurements taken at scheduled trial visits from Day 3 to Day 364 were included in the analysis. The hypothesis to test was the following: a non-inferiority assessment determined whether degarelix was non-inferior to goserelin with respect to the cumulative probability of testosterone ≤0.5 ng/mL from Day 3 to Day 364.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	The non-inferiority limit for the difference between treatments (degarelix versus goserelin acetate) was chosen to be -5 percentage points.
[3]	Other relevant estimation information:
	No text entered.

3. Secondary:

Serum Levels of Testosterone Over Time [ Time Frame: Baseline and after 1, 2, 3, 6 and 13 months ]

Measure Type	Secondary
Measure Title	Serum Levels of Testosterone Over Time
Measure Description	Median testosterone levels are presented as absolute values at Baseline (in Baseline measures) and after 1, 2, 3, 6 and 13 months (below). One treatment month equals 28 days.
Time Frame	Baseline and after 1, 2, 3, 6 and 13 months

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.
FAS.

Reporting Groups

	Description
Degarelix 240 mg/480 mg	Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).
Goserelin Acetate	Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).

Measured Values

	Degarelix 240 mg/480 mg	Goserelin Acetate
Participants Analyzed [Units: Participants]	565	282
Serum Levels of Testosterone Over Time [Units: ng/mL] Median (Full Range)
Month 1	0.10 (0.015 to 3.85)	0.16 (0.04 to 1.77)
Month 2	0.09 (0.015 to 0.41)	0.10 (0.015 to 0.5)
Month 3	0.09 (0.015 to 3.24)	0.09 (0.015 to 5.4)
Month 6	0.09 (0.015 to 1.57)	0.09 (0.015 to 0.32)
Month 13	0.11 (0.015 to 4.19)	0.09 (0.015 to 0.95)

No statistical analysis provided for Serum Levels of Testosterone Over Time

4. Secondary:

Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time [ Time Frame: Baseline and after 1, 2, 3, 6 and 13 months ]

Measure Type	Secondary
Measure Title	Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time
Measure Description	Serum PSA levels are presented as mean percent change from Baseline (in Baseline measures) after 1, 2, 3, 6 and 13 months. One treatment month equals 28 days.
Time Frame	Baseline and after 1, 2, 3, 6 and 13 months

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.
FAS.

Reporting Groups

	Description
Degarelix 240 mg/480 mg	Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).
Goserelin Acetate	Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).

Measured Values

	Degarelix 240 mg/480 mg	Goserelin Acetate
Participants Analyzed [Units: Participants]	565	282
Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time [Units: Percent change] Mean (Standard Deviation)
Month 1	-77 (23.7)	-57 (45.7)
Month 2	-89 (12.6)	-86 (18.1)
Month 3	-90 (15.4)	-86 (58.6)
Month 6	-90 (30.5)	-91 (18.2)
Month 13	-82 (104)	-77 (146)

No statistical analysis provided for Percent Change in Serum Levels of Prostate-specific Antigen (PSA) Over Time

5. Secondary:

Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline [ Time Frame: At baseline, 10 months and 13 months ]

Measure Type	Secondary
Measure Title	Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline
Measure Description	The SF-36 is a multi-purpose, short-form health survey with only 36 questions and with a minimum score of 0 and a maximum score of 100. The higher score the better health. It yields an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures and a preference-based health utility index. The SF-36 has proven useful in surveys of general and specific populations, comparing the relative burden of diseases, and in differentiating the health benefits produced by a wide range of different treatments.
Time Frame	At baseline, 10 months and 13 months

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.
FAS.

Reporting Groups

	Description
Degarelix 240 mg/480 mg	Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).
Goserelin Acetate	Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).

Measured Values

	Degarelix 240 mg/480 mg	Goserelin Acetate
Participants Analyzed [Units: Participants]	565	282
Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline [Units: Units on a scale] Mean (Standard Deviation)
Month 10	0.52 (11.1)	0.27 (10.6)
Month 13	0.18 (10.9)	-0.87 (9.76)

No statistical analysis provided for Change in Health-related Quality of Life (HRQoL), as Measured by Short Form-36 (SF-36) Score at Month 10 and Month 13 Compared to Baseline

6. Secondary:

Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline [ Time Frame: At baseline, 1 month, 4 months, 7 months and 13 months ]

Measure Type	Secondary
Measure Title	Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline
Measure Description	IPSS is used to assess severity of lower urinary tract symptoms and to monitor the progress of symptoms once treatment has been initiated. It contains 7 questions regarding incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia. Each question is assigned a score of 0-5 (i.e. the minimum total score is 0 and the maximum is 35). A score of "0" corresponds to a response of "not at all" for the first six symptoms and "none" for nocturia, and a score of 5 corresponds to a response of "almost always" for the first six symptoms and "5 times or more" for nocturia.
Time Frame	At baseline, 1 month, 4 months, 7 months and 13 months

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.
FAS.

Reporting Groups

	Description
Degarelix 240 mg/480 mg	Degarelix: The degarelix doses were administered by subcutaneous (s.c.) injections into the abdominal wall. A starting dose of 240 mg degarelix was administered on Day 0. One month later a maintenance dose of 480 mg was administered. This was repeated after 4, 7, and 10 months (ie a total of 5 administrations).
Goserelin Acetate	Goserelin acetate: The goserelin doses were administered by subcutaneous (s.c.) implants into the abdominal wall. An initial dose of 3.6 mg goserelin was administered on Day 0. One month later a subsequent dose of 10.8 mg was administered and this was repeated after 4, 7, and 10 months (ie a total of 5 implants).

Measured Values

	Degarelix 240 mg/480 mg	Goserelin Acetate
Participants Analyzed [Units: Participants]	565	282
Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline [Units: Units on a scale] Mean (Standard Deviation)
Month 1	-1.06 (6.27)	-0.21 (6.22)
Month 4	-2.31 (6.65)	-1.74 (6.16)
Month 7	-2.47 (6.94)	-2.45 (6.80)
Month 13	-2.04 (7.28)	-1.52 (6.25)

No statistical analysis provided for Change in International Prostate Symptom Score (IPSS) Score at Months 1, 4, 7, and 13 Compared to Baseline

Serious Adverse Events

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Other Adverse Events

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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:

	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. Restriction Description: The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.

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:	NCT00946920 History of Changes
Other Study ID Numbers:	FE200486 CS35 2008-005276-27 ( EudraCT Number )
Study First Received:	July 3, 2009
Results First Received:	February 14, 2014
Last Updated:	May 2, 2014